Trial Outcomes & Findings for A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas (NCT NCT01512758)

NCT ID: NCT01512758

Last Updated: 2019-03-15

Results Overview

MTD was defined as highest dose at which \<2 participants experienced a dose-limiting toxicity (DLT). DLT was defined as any of the following events considered possibly related to therapy with alisertib by the investigator: 1. Grade 4 neutropenia (absolute neutrophil count \<500 cells/mm\^3) for \>7 days; 2. Grade 4 neutropenia with fever (oral or ear temperature ≥38.5°C); 3. Grade 4 thrombocytopenia (platelets \<25,000/mm\^3) for \>7 days; 4. Platelet count \<10,000 cells/mm\^3; 5. ≥Grade 3 thrombocytopenia with clinically significant bleeding; 6. Delay in initiation of subsequent cycle by \>7 days due to treatment-related toxicity; 7. ≥Grade 3 nonhematological toxicity except following: a. ≥Grade 3 nausea and/or emesis in the absence of optimal antiemetic therapy; b. ≥Grade 3 diarrhea in the absence of optimal supportive therapy; c. Grade 3 fatigue lasting \<1 week; d. Other Grade 3 nonhematological toxicity that can be safely and reliably controlled to ≤Grade 2 with appropriate treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 36 participants
• Primary outcome timeframe: Treatment Cycle 1
• Results posted on: 2019-03-15

Participant Flow

Participants took part in the study at 8 investigative sites in Singapore, Taiwan, Hong Kong, and South Korea from 06 February 2012 to 08 October 2013.

Participants with a diagnosis of advanced solid tumors or lymphomas received alisertib 30 mg or 40 mg twice a day (BID) for 7 consecutive days followed by a 14-day rest period in 21-day cycles (28-day cycles with additional 7-day rest period if all alisertib-related toxicities [except alopecia] were not resolved to less than Grade 2).

Participant milestones

Measure	Alisertib 30 mg Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.	Alisertib 40 mg Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Study STARTED	30	6
Overall Study COMPLETED	30	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas

Baseline characteristics by cohort

Measure	Alisertib 30 mg n=30 Participants Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.	Total n=36 Participants Total of all reporting groups
Age, Continuous	57.2 years STANDARD_DEVIATION 9.52 • n=5 Participants	50.7 years STANDARD_DEVIATION 18.25 • n=7 Participants	56.1 years STANDARD_DEVIATION 11.35 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	4 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Chinese)	17 Participants n=5 Participants	5 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Korean)	13 Participants n=5 Participants	0 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Malay	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	30 Participants n=5 Participants	6 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment Singapore	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Taiwan	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Hong Kong	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Korea, Republic of	13 Participants n=5 Participants	0 Participants n=7 Participants	13 Participants n=5 Participants
Height	162.5 cm STANDARD_DEVIATION 6.84 • n=5 Participants	161.9 cm STANDARD_DEVIATION 6.61 • n=7 Participants	162.4 cm STANDARD_DEVIATION 6.71 • n=5 Participants
Weight	57.78 kg STANDARD_DEVIATION 9.255 • n=5 Participants	62.30 kg STANDARD_DEVIATION 11.714 • n=7 Participants	58.53 kg STANDARD_DEVIATION 9.669 • n=5 Participants
Body Surface Area (BSA)	1.611 m^2 STANDARD_DEVIATION 0.1487 • n=5 Participants	1.667 m^2 STANDARD_DEVIATION 0.1613 • n=7 Participants	1.620 m^2 STANDARD_DEVIATION 0.1499 • n=5 Participants

PRIMARY outcome

Timeframe: Treatment Cycle 1

Population: DLT-Evaluable population is defined as participants with a common race who had not used granulocyte colony-stimulating factor (G-CSF) in cycle 1, and either experienced DLT during Cycle 1 or received at least 85% of planned doses of alisertib and have sufficient follow up data to allow investigator and sponsor to determine whether a DLT occurred.

MTD was defined as highest dose at which <2 participants experienced a dose-limiting toxicity (DLT). DLT was defined as any of the following events considered possibly related to therapy with alisertib by the investigator: 1. Grade 4 neutropenia (absolute neutrophil count <500 cells/mm^3) for >7 days; 2. Grade 4 neutropenia with fever (oral or ear temperature ≥38.5°C); 3. Grade 4 thrombocytopenia (platelets <25,000/mm^3) for >7 days; 4. Platelet count <10,000 cells/mm^3; 5. ≥Grade 3 thrombocytopenia with clinically significant bleeding; 6. Delay in initiation of subsequent cycle by >7 days due to treatment-related toxicity; 7. ≥Grade 3 nonhematological toxicity except following: a. ≥Grade 3 nausea and/or emesis in the absence of optimal antiemetic therapy; b. ≥Grade 3 diarrhea in the absence of optimal supportive therapy; c. Grade 3 fatigue lasting <1 week; d. Other Grade 3 nonhematological toxicity that can be safely and reliably controlled to ≤Grade 2 with appropriate treatment.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=8 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)	30 mg	—

PRIMARY outcome

Timeframe: First dose to 30 days past last dose (Up to 12.1 Months)

Population: Safety Population is defined as all participants who received at least one dose of alisertib.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=30 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Number of Participants With Adverse Events and Serious Adverse Events AE	30 Participants	6 Participants
Number of Participants With Adverse Events and Serious Adverse Events SAE	15 Participants	4 Participants

PRIMARY outcome

Timeframe: First dose to 30 days past last dose (Up to 12.1 Months)

Population: Safety Population is defined as all participants who received at least one dose of alisertib.

Laboratory AEs in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, investigations, and metabolism and nutrition disorders. An abnormal laboratory value was assessed as an AE if that value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A treatment¬-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=30 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Neutropenia	19 Participants	5 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events White blood cell count decreased	7 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Aspartate aminotransferase increased	6 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Neutrophil count decreased	4 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Alanine aminotransferase increased	4 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Platelet count decreased	3 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Haemoglobin decreased	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Blood creatinine increased	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Urine output decreased	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Hypokalaemia	4 Participants	3 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Blood bilirubin increased	2 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Hypercalcaemia	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Hyponatraemia	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Anaemia	9 Participants	4 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Thrombocytopenia	6 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Febrile neutropenia	4 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Leukopenia	2 Participants	2 Participants

PRIMARY outcome

Timeframe: First dose to 30 days past last dose (Up to 12.1 Months)

Population: Safety Population is defined as all participants who received at least one dose of alisertib.

Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=30 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Events Hypotension	1 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Events Bradycardia	1 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Events Hypertension	1 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Events Pyrexia	8 Participants	1 Participants

PRIMARY outcome

Timeframe: Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose

Population: Pharmacokinetic (PK) Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters. "n" in the category is the number of participants with data available at the given time-point.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=30 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Cmax: Maximum Observed Concentration for Alisertib Day 1	1442.5 nM Standard Deviation 534.80	1871.7 nM Standard Deviation 429.62
Cmax: Maximum Observed Concentration for Alisertib Day 7	3000.0 nM Standard Deviation 1329.38	3686.7 nM Standard Deviation 885.45

PRIMARY outcome

Timeframe: Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose

Population: PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters. "n" in the category is the number of participants with data available at the given time-point.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=30 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Tmax: Time to First Occurrence of Cmax for Alisertib Day 1	3.0 hr Interval 2.0 to 8.0	2.0 hr Interval 2.0 to 3.0
Tmax: Time to First Occurrence of Cmax for Alisertib Day 7	2.9 hr Interval 1.0 to 6.0	2.0 hr Interval 1.0 to 3.0

PRIMARY outcome

Timeframe: Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose

Population: PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters. "n" in the category is the number of participants with data available at the given time-point.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=30 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval (τ) for Alisertib Day 1	9549.0 nM*hr Standard Deviation 4119.30	11811.7 nM*hr Standard Deviation 2845.76
AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval (τ) for Alisertib Day 7	24377.9 nM*hr Standard Deviation 13261.61	30683.3 nM*hr Standard Deviation 9575.68

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose

Population: PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.

Dose normalized AUCτ was obtained using AUCτ divided by alisertib dose in milligrams.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=28 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Dose Normalized AUCτ: Area Under the Concentration-Time Curve From Time 0 to Time t for Alisertib	812.9 nM*hr/mg Standard Deviation 441.90	766.8 nM*hr/mg Standard Deviation 238.88

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose

Population: PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=24 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
T1/2: Terminal Half-Life for Alisertib	16.750 hr Standard Deviation 8.1710	14.795 hr Standard Deviation 4.5715

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose

Population: PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=28 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Rac: Accumulation Ratio for Alisertib	2.830 ratio Standard Deviation 1.2955	2.690 ratio Standard Deviation 1.0638

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose

Population: PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=28 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
PTR: Peak Trough Ratio During a Dosing Interval, at Steady State for Alisertib	2.254 ratio Standard Deviation 0.6458	2.207 ratio Standard Deviation 0.3946

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose

Population: PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=28 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
CLss/F: Apparent Clearance After Extravascular Administration, at Steady State, Calculated Using AUCτ for Alisertib	2.9357 L/hr Standard Deviation 1.37091	2.8083 L/hr Standard Deviation 1.20259

SECONDARY outcome

Timeframe: Baseline and every 2 cycles for up to 24 months or until progressive disease

Population: Safety Population is defined as all participants who received at least one dose of alisertib.

Best overall response rate is defined as the percentage of participants with complete response (CR) and/or partial response (PR) as assessed by the Investigator using Lymphoma International Working Group (IWG) Criteria or Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT, PET or MRI. IWG criteria for CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. RECIST response criteria is defined as: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=30 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg n=6 Participants Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Best Overall Response Rate Based on Investigator Assessment CR	0 percentage of participants	0 percentage of participants
Best Overall Response Rate Based on Investigator Assessment PR	3 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: First documented response until disease progression; approximately 12 months

Population: Safety Population is defined as all participants who received at least one dose of alisertib. Participants with response were evaluated.

DOR is defined as the time from the date of first documentation of a CR response to the date of first documentation of PD according to IWG criteria or RECIST criteria 1.1. IWG PD is defined as PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. RECIST PD is defined as unequivocal progression of existing non-target lesions.

Outcome measures

Measure	Alisertib 30 mg or 40 mg n=1 Participants Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).	Alisertib 40 mg Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Duration of Response	169 days Interval 169.0 to 169.0	—

SECONDARY outcome

Timeframe: Cycle 1, Day 1; at end of Cycle 2 and every 2 cycles thereafter; and at end treatment; approximately 12 months

Population: Data was not analyzed as per the change in planned analysis (protocol amendment).

Outcome measures

Outcome data not reported

Adverse Events

Alisertib 30 mg

Serious events: 15 serious events

Other events: 30 other events

Deaths: 0 deaths

Alisertib 40 mg

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Alisertib 30 mg n=30 participants at risk Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.	Alisertib 40 mg n=6 participants at risk Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Blood and lymphatic system disorders Febrile neutropenia	13.3% 4/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Upper gastrointestinal haemorrhage	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Small intestinal obstruction	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Bacteraemia	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Sepsis	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Subcutaneous abscess	0.00% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Neutrophil count decreased	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Lower extremity mass	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Axillary mass	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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) Cholangiocarcinoma	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Pneumonia aspiration	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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

Measure	Alisertib 30 mg n=30 participants at risk Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.	Alisertib 40 mg n=6 participants at risk Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Gastrointestinal disorders Diarrhoea	56.7% 17/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	53.3% 16/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	20.0% 6/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	23.3% 7/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	20.0% 6/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	16.7% 5/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Mouth ulceration	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 discomfort	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 ulcer	0.00% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Gingival pain	0.00% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	63.3% 19/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	26.7% 8/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	20.0% 6/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	46.7% 14/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	23.3% 7/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 maculo-papular	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Skin hyperpigmentation	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Pigmentation disorder	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Fatigue	40.0% 12/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	23.3% 7/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	16.7% 5/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Injection site pain	0.00% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 White blood cell count decreased	23.3% 7/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	20.0% 6/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	13.3% 4/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Neutrophil count decreased	13.3% 4/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	0.00% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Decreased appetite	26.7% 8/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	13.3% 4/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	13.3% 4/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Lethargy	0.00% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	3.3% 1/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Upper respiratory tract infection	10.0% 3/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	13.3% 4/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Cataract	0.00% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Immune system disorders Contrast media allergy	6.7% 2/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and abnormal laboratory findings. 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 Skin wound	0.00% 0/30 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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 • First dose to 30 days past last dose (Up to 12.1 Months) At each visit the Investigator had to document any occurrence of adverse events and 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: trialdisclosures@takeda.com

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