Trial Outcomes & Findings for A Phase I Clinical and Pharmacodynamic Study of MLN8237, A Novel Aurora A Kinase Inhibitor, in Participants With Advanced Malignancies (NCT NCT00651664)

Last Updated: 2019-03-15

Results Overview

DLT was evaluated using the National Cancer Institutes Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0; defined as any of the following events related to alisertib therapy: 1. Grade 4 neutropenia lasting for ≥7 consecutive days during recovery 2. Grade 4 neutropenia with fever and/or infection 3. Confirmed platelet count \<25,000/mm\^3 4. ≥Grade 3 nausea and/or emesis despite the use of an antiemetic prophylaxis 5. ≥Grade 3 diarrhea that occurred despite therapy with loperamide 6. Any other Grade 3 or greater nonhematologic toxicity, with the following exceptions: Grade 3 arthralgia/myalgias, Any grade of alopecia, Brief (\< 1 week) Grade 3 fatigue 7. Treatment delay of \>1 week because of a failure of adequate hematologic or nonhematologic recovery from the previous cycle of treatment. 8. Other alisertib-related nonhematologic toxicities ≥ Grade 2 that, in the opinion of the investigator, required a dose reduction or discontinuation of therapy with alisertib.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

59 participants

Primary outcome timeframe

First dose through 30 days following the last dose of study drug (up to 730 days)

Results posted on

2019-03-15

Participant Flow

Participants took part in the study at 2 investigative sites in Spain from 22 October 2007 to 05 April 2011.

Participants with a diagnosis of advanced malignancies were enrolled in a dose escalation study, alisertib 5, 80 150 mg once daily (QD) for 7 days; 50, 60, 75, 100 mg twice daily for 7 days; 50 mg QD for 14 days; 50, 70 mg QD for 21 days.

Participant milestones

Participant milestones
Measure	Alisertib 5 mg QD 7D Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Study STARTED	3	3	3	14	6	3	6	7	7	7
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	3	3	3	14	6	3	6	7	7	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Alisertib 5 mg QD 7D Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Study Occurrence of Adverse Event(s)	0	0	0	0	0	0	1	0	1	0
Overall Study Unsatisfactory Therapeutic Response	0	0	0	0	1	1	0	1	0	1
Overall Study Progressive Disease	3	3	3	12	4	1	3	6	5	5
Overall Study Patient Declined Further Treatment	0	0	0	1	1	1	0	0	0	1
Overall Study Symptomatic Deterioration	0	0	0	1	0	0	1	0	1	0
Overall Study Reason not Specified	0	0	0	0	0	0	1	0	0	0

Baseline Characteristics

A Phase I Clinical and Pharmacodynamic Study of MLN8237, A Novel Aurora A Kinase Inhibitor, in Participants With Advanced Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=14 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D n=7 Participants Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D n=7 Participants Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D n=7 Participants Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).	Total n=59 Participants Total of all reporting groups
Age, Continuous	52.7 years STANDARD_DEVIATION 9.07 • n=5 Participants	62.3 years STANDARD_DEVIATION 13.80 • n=7 Participants	55.7 years STANDARD_DEVIATION 20.79 • n=5 Participants	62.5 years STANDARD_DEVIATION 11.67 • n=4 Participants	59.2 years STANDARD_DEVIATION 18.74 • n=21 Participants	48.3 years STANDARD_DEVIATION 14.84 • n=8 Participants	58.7 years STANDARD_DEVIATION 8.69 • n=8 Participants	58.0 years STANDARD_DEVIATION 13.83 • n=24 Participants	53.0 years STANDARD_DEVIATION 11.08 • n=42 Participants	64.7 years STANDARD_DEVIATION 5.53 • n=42 Participants	58.8 years STANDARD_DEVIATION 12.46 • n=42 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants	2 Participants n=24 Participants	3 Participants n=42 Participants	2 Participants n=42 Participants	22 Participants n=42 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=8 Participants	4 Participants n=8 Participants	5 Participants n=24 Participants	4 Participants n=42 Participants	5 Participants n=42 Participants	37 Participants n=42 Participants
Race/Ethnicity, Customized Hispanic/Latino	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	14 participants n=4 Participants	6 participants n=21 Participants	3 participants n=8 Participants	6 participants n=8 Participants	7 participants n=24 Participants	6 participants n=42 Participants	5 participants n=42 Participants	56 participants n=42 Participants
Race/Ethnicity, Customized Not Hispanic/Latino	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	0 participants n=24 Participants	1 participants n=42 Participants	2 participants n=42 Participants	3 participants n=42 Participants
Race/Ethnicity, Customized	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	14 participants n=4 Participants	6 participants n=21 Participants	3 participants n=8 Participants	6 participants n=8 Participants	7 participants n=24 Participants	7 participants n=42 Participants	7 participants n=42 Participants	59 participants n=42 Participants
Region of Enrollment Spain	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	14 participants n=4 Participants	6 participants n=21 Participants	3 participants n=8 Participants	6 participants n=8 Participants	7 participants n=24 Participants	7 participants n=42 Participants	7 participants n=42 Participants	59 participants n=42 Participants
Height	164.0 cm STANDARD_DEVIATION 7.21 • n=5 Participants	164.3 cm STANDARD_DEVIATION 10.79 • n=7 Participants	167.3 cm STANDARD_DEVIATION 1.53 • n=5 Participants	165.8 cm STANDARD_DEVIATION 9.26 • n=4 Participants	160.5 cm STANDARD_DEVIATION 4.76 • n=21 Participants	171.3 cm STANDARD_DEVIATION 10.26 • n=8 Participants	165.2 cm STANDARD_DEVIATION 10.21 • n=8 Participants	169.9 cm STANDARD_DEVIATION 10.92 • n=24 Participants	160.4 cm STANDARD_DEVIATION 11.57 • n=42 Participants	167.6 cm STANDARD_DEVIATION 8.40 • n=42 Participants	165.4 cm STANDARD_DEVIATION 9.15 • n=42 Participants
Weight	83.7 kg STANDARD_DEVIATION 32.13 • n=5 Participants	75.2 kg STANDARD_DEVIATION 10.56 • n=7 Participants	70.3 kg STANDARD_DEVIATION 4.24 • n=5 Participants	74.4 kg STANDARD_DEVIATION 16.48 • n=4 Participants	64.8 kg STANDARD_DEVIATION 6.83 • n=21 Participants	90.5 kg STANDARD_DEVIATION 7.74 • n=8 Participants	69.6 kg STANDARD_DEVIATION 16.22 • n=8 Participants	76.7 kg STANDARD_DEVIATION 15.06 • n=24 Participants	69.1 kg STANDARD_DEVIATION 14.78 • n=42 Participants	77.9 kg STANDARD_DEVIATION 11.91 • n=42 Participants	74.0 kg STANDARD_DEVIATION 14.95 • n=42 Participants
Body Surface Area (BSA)	1.93 m^2 STANDARD_DEVIATION 0.393 • n=5 Participants	1.85 m^2 STANDARD_DEVIATION 0.191 • n=7 Participants	1.81 m^2 STANDARD_DEVIATION 0.047 • n=5 Participants	1.85 m^2 STANDARD_DEVIATION 0.225 • n=4 Participants	1.70 m^2 STANDARD_DEVIATION 0.102 • n=21 Participants	2.07 m^2 STANDARD_DEVIATION 0.098 • n=8 Participants	1.78 m^2 STANDARD_DEVIATION 0.244 • n=8 Participants	1.87 m^2 STANDARD_DEVIATION 0.204 • n=24 Participants	1.75 m^2 STANDARD_DEVIATION 0.231 • n=42 Participants	1.90 m^2 STANDARD_DEVIATION 0.145 • n=42 Participants	1.84 m^2 STANDARD_DEVIATION 0.208 • n=42 Participants

PRIMARY outcome

Timeframe: First dose through 30 days following the last dose of study drug (up to 730 days)

Population: DLT Evaluable Population was defined as all participants who received at least 75% of their planned alisertib doses for their first cycle of treatment (unless interrupted by DLT) and had sufficient follow-up data to allow the investigators and sponsor to determine whether DLT occurred.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=12 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=2 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D n=6 Participants Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D n=7 Participants Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D n=6 Participants Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Number of Participants With Dose-Limiting Toxicity (DLT)	0 participants	0 participants	0 participants	0 participants	2 participants	2 participants	3 participants	1 participants	1 participants	3 participants

PRIMARY outcome

Timeframe: Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days)

The MTD was defined as the highest dose at which DLT occurred in 0/3 or 1/6 participants.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=54 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Maximum Tolerated Dose (MTD) of Alisertib	50 mg BID for 7 Days	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Day 7

Population: Pharmacokinetic (PK) Evaluable Population was defined as all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=14 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Cmax: Maximum Observed Concentration for Alisertib 7 Day Dosing Day 1	123.15 nanomolar (nM) Geometric Coefficient of Variation 6.554	1774.12 nanomolar (nM) Geometric Coefficient of Variation 36.496	2014.81 nanomolar (nM) Geometric Coefficient of Variation 22.038	1035.3 nanomolar (nM) Geometric Coefficient of Variation 75.70	1536.1 nanomolar (nM) Geometric Coefficient of Variation 44.70	1266.6 nanomolar (nM) Geometric Coefficient of Variation 45.69	3196.4 nanomolar (nM) Geometric Coefficient of Variation 51.11	—	—	—
Cmax: Maximum Observed Concentration for Alisertib 7 Day Dosing Day 7	109.13 nanomolar (nM) Geometric Coefficient of Variation 34.458	1502.89 nanomolar (nM) Geometric Coefficient of Variation 32.818	4136.24 nanomolar (nM) Geometric Coefficient of Variation 26.253	1964.4 nanomolar (nM) Geometric Coefficient of Variation 46.26	3412.5 nanomolar (nM) Geometric Coefficient of Variation 27.06	5710.4 nanomolar (nM) Geometric Coefficient of Variation 23.89	4694.2 nanomolar (nM) Geometric Coefficient of Variation 38.86	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Day 7

Population: PK Evaluable Population was defined as all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=14 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Tmax: Time of First Occurrence of Cmax for Alisertib 7 Day Dosing Day 1	1.920 hour(hr) Interval 1.58 to 2.0	2.730 hour(hr) Interval 1.7 to 4.0	4.000 hour(hr) Interval 2.0 to 5.9	2.040 hour(hr) Interval 2.0 to 6.17	2.000 hour(hr) Interval 2.0 to 4.08	2.000 hour(hr) Interval 2.0 to 2.1	3.835 hour(hr) Interval 1.98 to 4.08	—	—	—
Tmax: Time of First Occurrence of Cmax for Alisertib 7 Day Dosing Day 7	1.670 hour(hr) Interval 1.0 to 1.97	1.580 hour(hr) Interval 1.5 to 6.0	1.550 hour(hr) Interval 1.42 to 3.43	2.000 hour(hr) Interval 1.25 to 8.0	2.000 hour(hr) Interval 0.92 to 4.0	4.170 hour(hr) Interval 1.75 to 5.83	1.580 hour(hr) Interval 1.0 to 6.0	—	—	—

SECONDARY outcome

Timeframe: Cycle1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Day 7

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=14 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib 7 Day Dosing Day 1	975.0 nM*hour(h) Geometric Coefficient of Variation NA CV was not calculated for 1 participant.	18204.2 nM*hour(h) Geometric Coefficient of Variation 36.19	27262.7 nM*hour(h) Geometric Coefficient of Variation 38.0	6314.1 nM*hour(h) Geometric Coefficient of Variation 82.32	9771.5 nM*hour(h) Geometric Coefficient of Variation 53.77	6895.3 nM*hour(h) Geometric Coefficient of Variation 9.21	16541.5 nM*hour(h) Geometric Coefficient of Variation 65.99	—	—	—
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib 7 Day Dosing Day 7	658.5 nM*hour(h) Geometric Coefficient of Variation 35.64	16101.6 nM*hour(h) Geometric Coefficient of Variation 38.81	48421.8 nM*hour(h) Geometric Coefficient of Variation 36.53	17795.6 nM*hour(h) Geometric Coefficient of Variation 43.87	25853.3 nM*hour(h) Geometric Coefficient of Variation 41.44	51684.4 nM*hour(h) Geometric Coefficient of Variation 24.87	40166.7 nM*hour(h) Geometric Coefficient of Variation 51.90	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Day 7 or 8 (BID arms)

Population: Participants from the PK Evaluable Population, all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available for t1/2 analysis.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=2 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=9 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Terminal Half-Life (t1/2) for Alisertib 7 Day Dosing	—	18.25 hr Standard Deviation 8.697	19.80 hr Standard Deviation 6.129	15.913 hr Standard Deviation 6.4766	19.475 hr Standard Deviation 15.5019	18.500 hr Standard Deviation 7.6295	13.637 hr Standard Deviation 6.8712	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Day 7

Rac for Day 7=AUCt Day 7/AUCt Day 1.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=1 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=8 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=4 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=2 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=4 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Accumulation Ratio (Rac) for Alisertib 7 Day Dosing	0.874 ratio Standard Deviation 0	0.892 ratio Standard Deviation 0.1331	1.954 ratio Standard Deviation 0.9092	2.295 ratio Standard Deviation 0.9846	2.583 ratio Standard Deviation 0.8959	7.765 ratio Standard Deviation 1.9163	2.350 ratio Standard Deviation 1.4926	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Day 7

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=2 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=9 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=5 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Peak/Trough Ratio for Aliserib 7 Day Dosing	5.950 ratio Standard Deviation 0.3253	4.650 ratio Standard Deviation 0.2163	4.507 ratio Standard Deviation 0.3029	3.083 ratio Standard Deviation 2.2296	3.050 ratio Standard Deviation 1.4056	1.867 ratio Standard Deviation 0.6009	2.256 ratio Standard Deviation 1.2013	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Day 7

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=9 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=5 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
CLss/F: Apparent Oral Clearance at Steady State 7 Day Dosing	14.055 liter(L)/hr Geometric Coefficient of Variation 27.6995	9.604 liter(L)/hr Geometric Coefficient of Variation 35.5110	5.967 liter(L)/hr Geometric Coefficient of Variation 31.2592	5.414 liter(L)/hr Geometric Coefficient of Variation 57.9221	4.182 liter(L)/hr Geometric Coefficient of Variation 51.2761	2.795 liter(L)/hr Geometric Coefficient of Variation 23.5794	4.798 liter(L)/hr Geometric Coefficient of Variation 49.4182	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Days 7 and 14

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Cmax: Maximum Observed Concentration for Alisertib 14 Day Dosing Day 1	1145.4 nM Geometric Coefficient of Variation 53.09	—	—	—	—	—	—	—	—	—
Cmax: Maximum Observed Concentration for Alisertib 14 Day Dosing Day 7	1418.1 nM Geometric Coefficient of Variation 70.96	—	—	—	—	—	—	—	—	—
Cmax: Maximum Observed Concentration for Alisertib 14 Day Dosing Day 14	1671.1 nM Geometric Coefficient of Variation 51.66	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Days 7 and 14

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Tmax: Time of First Occurrence of Cmax for Alisertib 14 Day Dosing Day 1	2.030 hr Interval 1.0 to 6.0	—	—	—	—	—	—	—	—	—
Tmax: Time of First Occurrence of Cmax for Alisertib 14 Day Dosing Day 7	2.000 hr Interval 2.0 to 4.0	—	—	—	—	—	—	—	—	—
Tmax: Time of First Occurrence of Cmax for Alisertib 14 Day Dosing Day 14	2.000 hr Interval 1.02 to 4.0	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Days 7 and 14

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib 14 Day Dosing Day 1	15363.0 nM*hr Geometric Coefficient of Variation 24.82	—	—	—	—	—	—	—	—	—
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib 14 Day Dosing Day 7	17918.8 nM*hr Geometric Coefficient of Variation 78.55	—	—	—	—	—	—	—	—	—
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib 14 Day Dosing Day 14	16449.8 nM*hr Geometric Coefficient of Variation 59.87	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Days 7 and 14

Population: Participants from the PK Evaluable Population, all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data for analysis of t1/2. No data was available for analysis at Day 7.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=5 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Terminal Half-Life (t1/2) for Alisertib 14 Day Dosing	26.62 hr Standard Deviation 13.611	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Days 7 and 14

Population: Participants from the PK Evaluable Population, all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available for analysis Rac. Here number analyzed is the number of participants with data available for analysis at the given time point.

Rac for Day 7=AUCt Day 7/AUCt Day 1. Rac for Day 14=AUCt Day 7/AUCt Day 1.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Accumulation Ratio (Rac) for Alisertib 14 Day Dosing Day 7	1.671 ratio Standard Deviation 0.8242	—	—	—	—	—	—	—	—	—
Accumulation Ratio (Rac) for Alisertib 14 Day Dosing Day 14	1.813 ratio Standard Deviation 0.5001	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Days 7 and 14

Population: Participants from the PK Evaluable Population, all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available for analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Peak/Trough Ratio for Aliserib 14 Day Dosing Day 7	4.415 ratio Standard Deviation 2.5016	—	—	—	—	—	—	—	—	—
Peak/Trough Ratio for Aliserib 14 Day Dosing Day 14	7.412 ratio Standard Deviation 4.2472	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Days 7 and 14

Population: Participants from the PK Evaluable Population, all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available for CLss/F analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
CLss/F: Apparent Oral Clearance at Steady State 14 Day Dosing Day 7	5.381 L/hr Geometric Coefficient of Variation 92.8272	—	—	—	—	—	—	—	—	—
CLss/F: Apparent Oral Clearance at Steady State 14 Day Dosing Day 14	5.856 L/hr Geometric Coefficient of Variation 98.2758	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Days 14 and 21

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Cmax: Maximum Observed Concentration for Alisertib 21 Day Dosing Day 1	1112.3 nM Geometric Coefficient of Variation 42.99	2220.3 nM Geometric Coefficient of Variation 47.57	—	—	—	—	—	—	—	—
Cmax: Maximum Observed Concentration for Alisertib 21 Day Dosing Day 14	1524.1 nM Geometric Coefficient of Variation 64.25	2595.0 nM Geometric Coefficient of Variation 42.98	—	—	—	—	—	—	—	—
Cmax: Maximum Observed Concentration for Alisertib 21 Day Dosing Day 21	1651.7 nM Geometric Coefficient of Variation 30.70	2093.7 nM Geometric Coefficient of Variation 11.68	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Days 14 and 21

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Tmax: Time of First Occurrence of Cmax for Alisertib 21 Day Dosing Day 1	4.000 hr Interval 2.0 to 6.17	2.000 hr Interval 2.0 to 2.02	—	—	—	—	—	—	—	—
Tmax: Time of First Occurrence of Cmax for Alisertib 21 Day Dosing Day 14	2.070 hr Interval 1.0 to 4.0	2.130 hr Interval 2.0 to 5.08	—	—	—	—	—	—	—	—
Tmax: Time of First Occurrence of Cmax for Alisertib 21 Day Dosing Day 21	2.100 hr Interval 2.0 to 24.8	2.125 hr Interval 2.0 to 2.33	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 24 hour) post-dose on Day 1 and Pre-dose and multiple time-points (up to 10 hours) on Days 14 and 21

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib 21 Day Dosing Day 1	11701.0 nM*hr Geometric Coefficient of Variation 49.78	18953.4 nM*hr Geometric Coefficient of Variation 56.89	—	—	—	—	—	—	—	—
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib 21 Day Dosing Day 14	20262.8 nM*hr Geometric Coefficient of Variation 71.34	30918.3 nM*hr Geometric Coefficient of Variation 55.68	—	—	—	—	—	—	—	—
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib 21 Day Dosing Day 21	18264.9 nM*hr Geometric Coefficient of Variation 28.67	24515.6 nM*hr Geometric Coefficient of Variation 23.80	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Day 21

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=6 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Terminal Half-Life (t1/2) for Alisertib 21 Day Dosing	20.13 hr Standard Deviation 6.326	26.13 hr Standard Deviation 9.780	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Days 14 and 21

Population: Participants from the PK Evaluable Population, all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available for analysis Rac. Here number analyzed is the number of participants with data available for analysis at the given time point.

Rac for Day 7=AUCt Day 7/AUCt Day 1. Rac for Day 14=AUCt Day 7/AUCt Day 1. Rac for Day 21=AUCt Day 21/AUCt Day 1.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Accumulation Ratio (Rac) for Alisertib 21 Day Dosing Day 14	2.482 ratio Standard Deviation 2.7166	2.103 ratio Standard Deviation 0.3861	—	—	—	—	—	—	—	—
Accumulation Ratio (Rac) for Alisertib 21 Day Dosing Day 21	1.678 ratio Standard Deviation 0.7587	1.933 ratio Standard Deviation 1.1104	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Days 14 and 21

Population: Participants from the PK Evaluable Population, all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available for analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Peak/Trough Ratio for Aliserib 21 Day Dosing Day 14	4.070 ratio Standard Deviation 2.4751	3.628 ratio Standard Deviation 0.4864	—	—	—	—	—	—	—	—
Peak/Trough Ratio for Aliserib 21 Day Dosing Day 21	4.792 ratio Standard Deviation 2.5652	4.658 ratio Standard Deviation 2.1825	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose and multiple time-points (up to 10 hours) on Days 14 and 21

Population: Participants from the PK Evaluable Population, all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available for CLss/F analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
CLss/F: Apparent Oral Clearance at Steady State 21 Day Dosing Day 14	4.753 L/hr Geometric Coefficient of Variation 70.5636	4.364 L/hr Geometric Coefficient of Variation 47.3164	—	—	—	—	—	—	—	—
CLss/F: Apparent Oral Clearance at Steady State 21 Day Dosing Day 21	5.276 L/hr Geometric Coefficient of Variation 28.1356	5.593 L/hr Geometric Coefficient of Variation 21.8384	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose (Baseline) and Day 1, 6 hours post-dose; Day 7, 6 and 24 hours post-dose.

Population: Pharmacodynamics Evaluable Population was defined as all participants who received at least first dose of alisertib, had a baseline skin punch biopsy sample, and had at least 1 additional skin punch biopsy taken during Cycle 1 of treatment. Here number analyzed is the number of participants with data available for analysis at the given time point.

Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 micrometer (µm) skin sections stained with fluorescent-tagged antibodies specific to 2 mitotic markers; histone H3 phosphorylated on serine 10 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=13 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 7 Day Dosing Day 1, 6 Hours Post-Dose	0.187 cells/mm Standard Deviation 0.0709	0.107 cells/mm Standard Deviation 0.0777	0.197 cells/mm Standard Deviation 0.0814	0.310 cells/mm Standard Deviation 0.2087	0.378 cells/mm Standard Deviation 0.4107	0.175 cells/mm Standard Deviation 0.2333	0.850 cells/mm Standard Deviation 1.0741	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 7 Day Dosing Day 7, 6 Hours Post-Dose	0.193 cells/mm Standard Deviation 0.1650	0.617 cells/mm Standard Deviation 0.7514	2.703 cells/mm Standard Deviation 0.7112	3.489 cells/mm Standard Deviation 2.6893	6.220 cells/mm Standard Deviation 5.7549	8.757 cells/mm Standard Deviation 4.0493	9.150 cells/mm Standard Deviation 8.9050	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 7 Day Dosing Day 7, 24 Hours Post-Dose	0.140 cells/mm Standard Deviation 0.1179	0.397 cells/mm Standard Deviation 0.2159	5.270 cells/mm Standard Deviation 3.8325	3.184 cells/mm Standard Deviation 4.4984	1.250 cells/mm Standard Deviation 0.0000	25.190 cells/mm Standard Deviation 1.7678	17.123 cells/mm Standard Deviation 9.4877	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose (Baseline) and Day 1 and 7, 6 hours post-dose; Day 14, 6 and 24 hours post-dose

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 14 Day Dosing Day 1, 6 Hours Post-Dose	1.180 cells/mm Standard Deviation 0.0000	—	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 14 Day Dosing Day 7, 6 Hours Post-Dose	0.950 cells/mm Standard Deviation 0.9963	—	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 14 Day Dosing Day 14, 6 Hours Post-Dose	1.146 cells/mm Standard Deviation 1.6239	—	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 14 Day Dosing Day 7, 24 Hours Post-Dose	0.368 cells/mm Standard Deviation 0.4464	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose (Baseline) and Day 7, 14 and 21, 6 hours post-dose

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 21 Day Dosing Day 7, 6 Hours Post-Dose	1.534 cells/mm Standard Deviation 1.9201	1.900 cells/mm Standard Deviation 2.2774	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 21 Day Dosing Day 14, 6 Hours Post-Dose	0.341 cells/mm Standard Deviation 0.3182	1.168 cells/mm Standard Deviation 0.7587	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Mitotic Index 21 Day Dosing Day 21, 6 Hours Post-Dose	0.250 cells/mm Standard Deviation 1.453	0.565 cells/mm Standard Deviation 0.5565	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Day 1, 6 hours post-dose; Days 7 6 and 24 hours post-dose; Day 21: 6 hours post-dose

Apoptotic index was defined as the mean number of apoptotic cells per mm length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µm skin sections stained with hematoxylin and eosin. A positive change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=13 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 7 Day Dosing Day 1, 6 hour post-dose	0.080 cells/mm Standard Deviation 0.0693	0.000 cells/mm Standard Deviation 0.0000	0.097 cells/mm Standard Deviation 0.0850	0.040 cells/mm Standard Deviation 0.0634	0.000 cells/mm Standard Deviation 0.0000	0.055 cells/mm Standard Deviation 0.0778	0.242 cells/mm Standard Deviation 0.2566	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 7 Day Dosing Day 7, 6 hour post-dose	0.040 cells/mm Standard Deviation 0.0693	0.560 cells/mm Standard Deviation 0.9699	1.303 cells/mm Standard Deviation 0.5950	1.525 cells/mm Standard Deviation 2.2399	3.173 cells/mm Standard Deviation 4.3170	6.040 cells/mm Standard Deviation 1.9928	5.162 cells/mm Standard Deviation 2.2801	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 7 Day Dosing Day 7, 24 hour post-dose	0.040 cells/mm Standard Deviation 0.0693	0.343 cells/mm Standard Deviation 0.4944	2.145 cells/mm Standard Deviation 1.6476	1.050 cells/mm Standard Deviation 1.749	0.830 cells/mm Standard Deviation 0.00	7.715 cells/mm Standard Deviation 0.1202	4.713 cells/mm Standard Deviation 1.1924	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose (Baseline) and Day 1, 6 hours post-dose; Days 7 and 14, 6 and 24 hours post-dose

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 14 Day Dosing Day 1, 6 hours post-dose	0.000 cells/mm Standard Deviation 0.000	—	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 14 Day Dosing Day 7, 6 hours post-dose	0.390 cells/mm Standard Deviation 0.8721	—	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 14 Day Dosing Day 14, 6 hours post-dose	0.484 cells/mm Standard Deviation 0.7869	—	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 14 Day Dosing Day 14, 24 hours post-dose	0.260 cells/mm Standard Deviation 0.3834	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose (Baseline) and Day 1, 6 hours post-dose; Days 7 and 14, 6 and 24 hours post-dose; Day 21: 6 hours post-dose

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 21 Day Dosing Day 7, 6 hours post-dose	0.606 cells/mm Standard Deviation 0.9954	0.379 cells/mm Standard Deviation 0.6276	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 21 Day Dosing Day 14, 6 hours post-dose	0.146 cells/mm Standard Deviation 0.2355	0.404 cells/mm Standard Deviation 0.4334	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Skin Punch Biopsy Apoptotic Index 21 Day Dosing Day 21, 6 hours post-dose	0.134 cells/mm Standard Deviation 0.1698	0.230 cells/mm Standard Deviation 0.1283	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose (Baseline) and Days 1 and 7, 6 hours post-dose

Tumor biopsy sections were immunoflourescently labeled with proliferative marker Ki67 and mitotic marker pHistH3. DNA was stained with a fluorescent marker as well. The Mitotic index was determined from the percentage of pHistH3 immunopositive cells within the Ki67 positive area. A positive change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=3 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=3 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=3 Participants Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=13 Participants Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=6 Participants Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=3 Participants Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=6 Participants Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Tumor Biopsy Mitotic Index 7 Day Dosing Day 1, 6 hours post-dose	0.125 percentage of cells Standard Deviation 0.1061	0.610 percentage of cells Standard Deviation 0.0000	6.460 percentage of cells Standard Deviation 9.1075	1.464 percentage of cells Standard Deviation 1.3294	1.080 percentage of cells Standard Deviation 0.3394	0.090 percentage of cells Standard Deviation 0.0000	2.907 percentage of cells Standard Deviation 2.0284	—	—	—
Change From Baseline in Alisertib Tumor Biopsy Mitotic Index 7 Day Dosing Day 7, 6 hours post-dose	1.145 percentage of cells Standard Deviation 0.0354	0.590 percentage of cells Standard Deviation 0.0000	15.500 percentage of cells Standard Deviation 13.5623	2.020 percentage of cells Standard Deviation 2.9567	3.115 percentage of cells Standard Deviation 3.1608	5.840 percentage of cells Standard Deviation 0.0000	3.527 percentage of cells Standard Deviation 2.1258	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose (Baseline) and Day 7, 6 hours post-dose

Population: Pharmacodynamics Evaluable Population was defined as all participants who received at least the first dose of alisertib, had a baseline skin punch biopsy sample, and had at least 1 additional skin punch biopsy taken during Cycle 1 of treatment.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Tumor Biopsy Mitotic Index 14 Day Dosing	0.008 percentage of cells Standard Deviation 0.0000	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1: Pre-dose (Baseline) and Days 7 and 21, 6 hours post-dose

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=7 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=7 Participants Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Change From Baseline in Alisertib Tumor Biopsy Mitotic Index 21 Day Dosing Day 7, 6 hours post-dose	0.027 percentage of cells Standard Deviation 0.0171	0.050 percentage of cells Standard Deviation 0.0243	—	—	—	—	—	—	—	—
Change From Baseline in Alisertib Tumor Biopsy Mitotic Index 21 Day Dosing Day 21, 6 hours post-dose	0.014 percentage of cells Standard Deviation 0.0072	0.054 percentage of cells Standard Deviation 0.0038	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle 1: Pre-dose

Population: Safety population was defined as all participants who received any amount of study drug. A blood sample was not evaluable for 3 participants and was missing for 5 participants. Data is presented for one arm because the data was collected prior to the participant receiving their assigned treatment.

A blood sample was collected prior to alisertib dosing for the purpose of genotyping for polymorphisms in UGT1A1. The percentage of participants in the polymorphism categories: wt/wt, wt/\*28, \*28/\*28, \*28/wt, \*28/other and other/other is reported. wt=wild type. \*28 polymorphism in the promoter region of a UGT1A1 allele resulting in reduced UGT1A1 expression.

Outcome measures

Outcome measures
Measure	Alisertib 5 mg QD 7D n=59 Participants Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Percentage of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 wt/wt	34 percentage of participants	—	—	—	—	—	—	—	—	—
Percentage of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 wt/*28	44 percentage of participants	—	—	—	—	—	—	—	—	—
Percentage of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 28/28	7 percentage of participants	—	—	—	—	—	—	—	—	—
Percentage of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 *28/wt	0 percentage of participants	—	—	—	—	—	—	—	—	—
Percentage of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 *28/other	0 percentage of participants	—	—	—	—	—	—	—	—	—
Percentage of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 other/other	2 percentage of participants	—	—	—	—	—	—	—	—	—

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alisertib 5 mg QD 7D n=39 participants at risk；n=3 participants at risk Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=30 participants at risk；n=3 participants at risk Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=101 participants at risk；n=3 participants at risk Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=142 participants at risk；n=14 participants at risk Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=68 participants at risk；n=6 participants at risk Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=68 participants at risk；n=3 participants at risk Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=194 participants at risk；n=6 participants at risk Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D n=119 participants at risk；n=7 participants at risk Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D n=67 participants at risk；n=7 participants at risk Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D n=68 participants at risk；n=7 participants at risk Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Enteritis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Escherichia urinary tract infection	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pneumonia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Respiratory tract infection	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Somnolence	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Spinal cord compression	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Incorrect dose administered	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Renal failure	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Bradyphrenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Other adverse events
Measure	Alisertib 5 mg QD 7D n=39 participants at risk；n=3 participants at risk Alisertib 5 mg, capsules, orally, once daily (QD) for 7 days (D) followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles).	Alisertib 80 mg QD 7D n=30 participants at risk；n=3 participants at risk Alisertib 80 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).	Alisertib 150 mg QD 7D n=101 participants at risk；n=3 participants at risk Alisertib 150 mg, capsules, orally, QD for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 50 mg BID 7D n=142 participants at risk；n=14 participants at risk Alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 29 cycles).	Alisertib 60 mg BID 7D n=68 participants at risk；n=6 participants at risk Alisertib 60 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).	Alisertib 75 mg BID 7D n=68 participants at risk；n=3 participants at risk Alisertib 75 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).	Alisertib 100 mg BID 7D n=194 participants at risk；n=6 participants at risk Alisertib 100 mg, capsules, orally, BID for 7 days followed by a 14-day recovery period in each 21-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 21 cycles).	Alisertib 50 mg QD 14D n=119 participants at risk；n=7 participants at risk Alisertib 50 mg, capsules, orally, QD for 14 days followed by a 14-day recovery period in each 28-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 25 cycles).	Alisertib 50 mg QD 21D n=67 participants at risk；n=7 participants at risk Alisertib 50 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 10 cycles).	Alisertib 70 mg QD 21D n=68 participants at risk；n=7 participants at risk Alisertib 70 mg, capsules, orally, QD for 21 days followed by a 14-day recovery period in each 35-day cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
General disorders Red man syndrome	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Somnolence	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 8 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 4/14 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 10 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	71.4% 5/7 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 8 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 4/6 • Number of events 9 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	71.4% 5/7 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	21.4% 3/14 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 2/14 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 9 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain upper	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Enteritis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	21.4% 3/14 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dry mouth	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Proctalgia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Rectal tenesmus	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Anal fissure	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Haematochezia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Aphthous stomatitis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Ascites	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Colonic haemorrhage	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Flatulence	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Haemorrhoids	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Odynophagia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Oral pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Perianal erythema	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Anaemia	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	57.1% 8/14 • Number of events 11 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 4/6 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	100.0% 3/3 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	83.3% 5/6 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	71.4% 5/7 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	57.1% 4/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 8 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	57.1% 8/14 • Number of events 11 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	100.0% 6/6 • Number of events 9 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	57.1% 4/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	100.0% 3/3 • Number of events 9 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 4/14 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 4/6 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 8 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	64.3% 9/14 • Number of events 11 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	85.7% 6/7 • Number of events 10 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	35.7% 5/14 • Number of events 8 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	83.3% 5/6 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Anorexia	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 8 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	57.1% 4/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	21.4% 3/14 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	35.7% 5/14 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	21.4% 3/14 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypercholesterolaemia	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	21.4% 3/14 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperproteinaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 2/14 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 2/14 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperchloraemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypermagnesaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 2/14 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypoproteinaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Fluid intake reduced	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypochloraemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	35.7% 5/14 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 4/6 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 7/14 • Number of events 8 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 4/14 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Gamma-glutamyltransferase increased	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 4/14 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatinine increased	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 2/14 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood bilirubin increased	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood urea increased	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 2/14 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Platelet count decreased	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatinine decreased	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Red blood cell count decreased	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Transaminases increased	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Weight decreased	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Asthenia	100.0% 3/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 9 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	21.4% 3/14 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	83.3% 5/6 • Number of events 10 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	85.7% 6/7 • Number of events 6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	57.1% 4/7 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	83.3% 5/6 • Number of events 8 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	57.1% 4/7 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Oedema peripheral	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Chills	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Chest pain	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Feeling jittery	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Gait disturbance	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebral ataxia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Aphonia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dysaesthesia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dysgeusia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Neuropathic pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Paraesthesia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	100.0% 3/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 4/6 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 4/6 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	42.9% 3/7 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	71.4% 5/7 • Number of events 5 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Exfoliative rash	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Rash	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Blister	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Onycholysis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Toxic skin eruption	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Oral candidiasis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Respiratory tract infection	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bronchitis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Catheter related infection	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Gastroenteritis escherichia coli	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Herpes simplex	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nail infection	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Urinary tract infection	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Shoulder pain	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	50.0% 3/6 • Number of events 4 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Confusional state	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Affect lability	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Anxiety	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Bradyphrenia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Nervousness	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Keratitis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	66.7% 2/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 2/6 • Number of events 12 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Dry eye	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Vision blurred	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	66.7% 2/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	28.6% 2/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Synovial sarcoma	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Hepatic pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 2/14 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 2 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Jaundice	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Haematuria	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Dysuria	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Oliguria	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Pollakiuria	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypotension	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Haematoma	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Phlebitis	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 1/6 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Incorrect dose administered	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Palpitations	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	33.3% 1/3 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Ear and labyrinth disorders Ear pain	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/3 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/6 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.3% 1/7 • Number of events 1 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/7 • Signing of the Informed Consent through 30 days following the last dose of study drug (up to 730 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Publication restrictions are in place

Restriction type: OTHER