Trial Outcomes & Findings for Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor. (NCT NCT02732119)

NCT ID: NCT02732119

Last Updated: 2021-05-05

Results Overview

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a reasonably possible relationship to the study medication(s) and is unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment (cycle 1) and meets any of the criteria defined in the protocol. National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 will be used for all grading.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 104 participants
• Primary outcome timeframe: Baseline up to 28 days
• Results posted on: 2021-05-05

Participant Flow

Cohort A, B and C were in Phase I and Group 1 and Group 2 classification were in Phase II

Participant milestones

Measure	Cohort A Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally	Group 1 Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Group 2 Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Phase I STARTED	8	10	7	0	0
Phase I COMPLETED	0	0	0	0	0
Phase I NOT COMPLETED	8	10	7	0	0
Phase II STARTED	0	0	0	46	33
Phase II Protocol Analysis Set	0	0	0	46	32
Phase II COMPLETED	0	0	0	0	0
Phase II NOT COMPLETED	0	0	0	46	33

Reasons for withdrawal

Measure	Cohort A Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally	Group 1 Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Group 2 Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Phase I Adverse Event	1	3	1	0	0
Phase I Progressive disease	7	3	2	0	0
Phase I Protocol deviation	0	1	0	0	0
Phase I Physician Decision	0	3	4	0	0
Phase II Adverse Event	0	0	0	3	3
Phase II Death	0	0	0	1	0
Phase II Progressive dissease	0	0	0	30	23
Phase II Study terminated by sponsor	0	0	0	2	2
Phase II Other	0	0	0	2	0
Phase II Physician Decision	0	0	0	8	5

Baseline Characteristics

Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor.

Baseline characteristics by cohort

Measure	Cohort A n=8 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=10 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C n=7 Participants Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally	Group 1 n=46 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Group 2 n=33 Participants Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally	Total n=104 Participants Total of all reporting groups
Age, Customized <40 years	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants	5 participants n=21 Participants	12 participants n=8 Participants
Age, Customized ≥ 40 - < 50 years	2 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	7 participants n=4 Participants	3 participants n=21 Participants	13 participants n=8 Participants
Age, Customized ≥ 50 - < 60 years	3 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	15 participants n=4 Participants	11 participants n=21 Participants	35 participants n=8 Participants
Age, Customized ≥ 60 - < 70 years	2 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	14 participants n=4 Participants	11 participants n=21 Participants	31 participants n=8 Participants
Age, Customized ≥ 70 years	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	6 participants n=4 Participants	3 participants n=21 Participants	13 participants n=8 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	10 Participants n=7 Participants	7 Participants n=5 Participants	46 Participants n=4 Participants	33 Participants n=21 Participants	104 Participants n=8 Participants
Sex: Female, Male Male	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
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	5 Participants n=8 Participants
Race/Ethnicity, Customized White/Caucasian	7 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	36 Participants n=4 Participants	30 Participants n=21 Participants	85 Participants n=8 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants	0 Participants n=21 Participants	7 Participants n=8 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=8 Participants
Body Mass Index < 30 BMI	5 participants n=5 Participants	7 participants n=7 Participants	2 participants n=5 Participants	26 participants n=4 Participants	19 participants n=21 Participants	59 participants n=8 Participants
Body Mass Index ≥ 30 BMI	3 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	18 participants n=4 Participants	11 participants n=21 Participants	39 participants n=8 Participants
Body Mass Index Missing	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants	6 participants n=8 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Performance = 0	4 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	27 Participants n=4 Participants	21 Participants n=21 Participants	57 Participants n=8 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Performance = 1	4 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants	12 Participants n=21 Participants	47 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 days

Population: dose limiting toxicity-determining set

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a reasonably possible relationship to the study medication(s) and is unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment (cycle 1) and meets any of the criteria defined in the protocol. National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 will be used for all grading.

Outcome measures

Measure	Cohort A n=8 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=10 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C n=7 Participants Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I Febrile neutropenia Grade 3	1 Participants	1 Participants	0 Participants
Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I Neutropenia Grade 4	0 Participants	1 Participants	0 Participants
Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I Thrombocytopenia Grade 4	0 Participants	1 Participants	0 Participants
Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I Cardiac tamponade Grade 4	1 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I Diarrhea Grade 3	1 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities by Preferred Term in Cycle 1 (28 Days) - in Phase I Hyperglycemia Grade 4	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: From baseline up to 24 weeks

Population: Protocol analysis set. n: Number of patients who are at the corresponding category. ORR: percentage of patients having BOR of CR/PR.

Clinical Benefit Rate (CBR) is defined as the percentage of participants with a complete response (CR) or partial response (PR) or with stable disease (SD) as per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 or Non-Complete Response or Non-Progressive Disease (NCRNPD) during first 24 weeks of first dose. CR=disappearance of all non-nodal target lesions, PR=at least a 30% decrease in the sum of diameter of all target lesions, SD=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD), PD=at least a 20% increase in the sum of diameter of all target lesions.

The hypothesis was to be rejected if the lower limit of the 95% Confidence Interval for Clinical Benefit Rate (CBR) was greater than 10%.

Outcome measures

Measure	Cohort A n=46 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=32 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Clinical Benefit Rate as Per Central Review by Group- Phase II Overall response rate (CR+PR):	6.5 percentage of participants Interval 1.4 to 17.9	9.4 percentage of participants Interval 2.0 to 25.0	—
Clinical Benefit Rate as Per Central Review by Group- Phase II CBR - CR+PR+SD (NCRNPD) by 24 weeks	65.2 percentage of participants Interval 49.8 to 78.6	59.4 percentage of participants Interval 40.6 to 76.3	—
Clinical Benefit Rate as Per Central Review by Group- Phase II Disease control rate (CR+PR+SD(NCRNPD)	65.2 percentage of participants Interval 49.8 to 78.6	59.4 percentage of participants Interval 40.6 to 76.3	—

PRIMARY outcome

Timeframe: Baseline up to 24 weeks and at 24 weeks

Population: Full analysis set

Complete response (CR) or partial response (PR), or stable disease (SD) at 24 weeks as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Non-CR Non-PD (NCRNPD) at Week 24.

Outcome measures

Measure	Cohort A n=46 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=32 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II Participants with measurable disease at baseline	35 Participants	21 Participants	—
Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II Participants with non-measurable disease at baseline	11 Participants	11 Participants	—
Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II Complete response (CR)	0 Participants	0 Participants	—
Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II Partial Response (PR)	3 Participants	3 Participants	—
Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II Stable disease (SD)	17 Participants	6 Participants	—
Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II Progressive disease (PD)	14 Participants	12 Participants	—
Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II NCRNPD - Non-complete response non-progressive disease	10 Participants	10 Participants	—
Best Overall Responses (BOR) Summary Table as Per Central Review by Group - Phase II Unknown	2 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Cycle 1,2: Day 1 and 15 - pre-dose, 2 and 4 hour post dose, Cycle 3 , Day 1 - pre-dose

Population: Pharmacokinetic analysis set. Number of participants with valid samples varied across timepoints and visits

Plasma concentrations; below limit of quantitation values set to zero

Outcome measures

Measure	Cohort A n=8 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=10 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C n=7 Participants Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I Cycle 1, Day 15 Pre-dose	7.82 ng/mL Interval 3.57 to 10.3	8.31 ng/mL Interval 1.68 to 14.8	8.28 ng/mL Interval 5.25 to 15.0
Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I Cycle 1, Day 15 2 H, post dose	15.2 ng/mL Interval 13.2 to 36.2	17 ng/mL Interval 6.84 to 34.4	36.2 ng/mL Interval 19.4 to 63.4
Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I Cycle 1, Day 15 4 H, post dose	17.7 ng/mL Interval 16.7 to 18.5	16.2 ng/mL Interval 4.69 to 20.7	21.5 ng/mL Interval 13.6 to 35.8
Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I Cycle 2, Day 1 Pre-dose	6.47 ng/mL Interval 5.63 to 11.5	6.22 ng/mL Interval 1.71 to 10.5	7.76 ng/mL Interval 4.58 to 15.4
Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I Cycle 2, Day 15 Pre-dose	5.89 ng/mL Interval 4.33 to 9.52	4.26 ng/mL Interval 0.82 to 8.02	7.17 ng/mL Interval 5.4 to 15.3
Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I Cycle 2, Day 15 2 H post-dose	21.8 ng/mL Interval 13.5 to 33.3	14.5 ng/mL Interval 8.67 to 30.1	22.1 ng/mL Interval 10.4 to 72.0
Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I Cycle 2, Day 15 4 H post-dose	13.7 ng/mL Interval 5.42 to 20.7	9.13 ng/mL Interval 6.62 to 15.7	26.9 ng/mL Interval 20.5 to 41.1
Everolimus Pharmacokinetic Plasma Concentrations by Cohort - Phase I Cycle 3, Day 1 4 H pre-dose	4.7 ng/mL Interval 3.05 to 9.98	6.97 ng/mL Interval 2.87 to 22.5	6.33 ng/mL Interval 4.8 to 7.85

SECONDARY outcome

Timeframe: From baseline up to 24 weeks

Complete response (CR) or partial response (PR), or stable disease (SD)as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Non-CR Non-PD (NCRNPD)

Outcome measures

Measure	Cohort A n=8 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=10 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C n=7 Participants Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I Participants with measurable disease at baseline	5 Participants	7 Participants	4 Participants
Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I Participants with non-measurable disease at baseline	3 Participants	3 Participants	3 Participants
Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I Complete response (CR)	0 Participants	0 Participants	0 Participants
Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I Partial Response (PR)	0 Participants	1 Participants	2 Participants
Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I Stable disease (SD)	3 Participants	6 Participants	2 Participants
Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I Progressive disease (PD)	3 Participants	0 Participants	0 Participants
Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I NCRNPD - Non-complete response non-progressive disease	2 Participants	1 Participants	3 Participants
Best Overall Responses (BOR) Summary Table as Per Central Review by Cohort - Phase I Unknown	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to 24 weeks and at week 24

Population: Protocol analysis set

Clinical Benefit Rate (CBR) is defined as the percentage of patients with a complete response (CR) or partial response (PR) or with stable disease (SD) at 24 weeks as per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 or Non-Complete Response Non-Progressive Disease (NCRNPD) up to Week 24 and at Week 24.

Outcome measures

Measure	Cohort A n=8 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=10 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C n=7 Participants Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Clinical Benefit Rate as Per Central Review by Dose Cohort - Phase I Overall response rate (CR+PR):	—	10.0 percentage of participants Interval 0.3 to 44.5	28.6 percentage of participants Interval 3.7 to 71.0
Clinical Benefit Rate as Per Central Review by Dose Cohort - Phase I CBR - CR+PR+SD (NCRNPD) by 24 weeks	62.5 percentage of participants Interval 24.5 to 91.5	80.0 percentage of participants Interval 44.4 to 97.5	100.0 percentage of participants Interval 59.0 to 100.0
Clinical Benefit Rate as Per Central Review by Dose Cohort - Phase I CBR - CR+PR+SD (NCRNPD) at 24 weeks	0 percentage of participants Interval 0.0 to 36.9	0.0 percentage of participants Interval 0.0 to 30.8	28.6 percentage of participants Interval 3.7 to 71.0
Clinical Benefit Rate as Per Central Review by Dose Cohort - Phase I Disease control rate (CR+PR+SD(NCRNPD)	62.5 percentage of participants Interval 24.5 to 91.5	80.0 percentage of participants Interval 44.4 to 97.5	100 percentage of participants Interval 59.0 to 100.0

SECONDARY outcome

Timeframe: Baseline up to approximately 32 months

Population: Full analysis set

Progression is defined as <= 12 weeks after randomization/ start of treatment (and not qualifying for CR, PR or SD).

Outcome measures

Measure	Cohort A n=46 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=32 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Summary of Progression-free Survival (PFS) (Months), as Per Central Review by Group - Phase II	8.0 months Interval 3.8 to 14.5	4.7 months Interval 2.0 to 12.7	—

SECONDARY outcome

Timeframe: Baseline up to approximately 32 months

Population: Full analysis set

Overall survival is the time from date of first treatment to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the last date of contact.

Outcome measures

Measure	Cohort A n=46 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=32 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Overall Survival (OS) by Group - Phase II	27.4 months Interval 16.8 to Not estimable - insufficient number of participants with events	NA months Interval 16.4 to Not estimable - insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Baseline up to approximately 16 months

Population: Full analysis set. N=number patients included in the analysis (with confirmed CR or PR)

Patients whose best response is complete response (CR) or partial response (PR). The start date is the date of first documented response (CR or PR) and the end date is the date of first documented progression or death due to underlying cancer.

Outcome measures

Measure	Cohort A n=3 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=3 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Duration of Overall Response (DOR) by Group - Phase II	14.6 months Not estimable - insufficient number of participants with confirmed response to calculate CI upper and lower limits	6.4 months Interval 5.5 to 7.4	—

SECONDARY outcome

Timeframe: Baseline up to approximately 8 months

Population: Full analysis set

Time to definitive deterioration of ECOG performance status in one category of score is defined as the time from the date of randomization to the date of event, which is defined as at least one score lower than the baseline.

Outcome measures

Measure	Cohort A n=46 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=32 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score by Group - Phase II	NA median Interval 7.4 to Not estimable - insufficient number of participants with events	12.0 median Interval 7.3 to Not estimable - insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Cycle 1,2: Day 1 and 15 - pre-dose, 2 and 4 hour post dose, Cycle 3 , Day 1 - pre-dose

Population: Pharmacokinetic analysis set. Number of participants with valid samples varied across timepoints and visits

Plasma concentrations; below limit of quantitation values set to zero

Outcome measures

Measure	Cohort A n=46 Participants Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=33 Participants Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Everolimus Pharmacokinetic Plasma Concentrations - Phase II Cycle 1, Day 15 pre dose	214 ng/mL Interval 13.8 to 1410.0	132 ng/mL Interval 45.2 to 296.0	—
Everolimus Pharmacokinetic Plasma Concentrations - Phase II Cycle 1, Day 15 2 H post-dose	644 ng/mL Interval 38.6 to 2490.0	372 ng/mL Interval 83.8 to 686.0	—
Everolimus Pharmacokinetic Plasma Concentrations - Phase II Cycle 1, Day 15 4 H post-dose	583 ng/mL Interval 34.3 to 2320.0	323 ng/mL Interval 81.3 to 631.0	—
Everolimus Pharmacokinetic Plasma Concentrations - Phase II Cycle 2 Day 1 pre-dose	199 ng/mL Interval 2.27 to 691.0	125 ng/mL Interval 1.4 to 379.0	—
Everolimus Pharmacokinetic Plasma Concentrations - Phase II Cycle 2, Day 15 pre-dose	245 ng/mL Interval 21.2 to 1350.0	170 ng/mL Interval 2.72 to 382.0	—
Everolimus Pharmacokinetic Plasma Concentrations - Phase II Cycle 2, Day 15 2 H post-dose	652 ng/mL Interval 140.0 to 2260.0	442 ng/mL Interval 2.34 to 1240.0	—
Everolimus Pharmacokinetic Plasma Concentrations - Phase II Cycle 2, Day 15 4 H post-dose	642 ng/mL Interval 133.0 to 2130.0	406 ng/mL Interval 2.1 to 1040.0	—
Everolimus Pharmacokinetic Plasma Concentrations - Phase II Cycle 3, Day 1 pre-dose	193 ng/mL Interval 1.52 to 1080.0	198 ng/mL Interval 2.61 to 504.0	—

Adverse Events

Cohort A

Serious events: 3 serious events

Other events: 8 other events

Deaths: 6 deaths

Cohort B

Serious events: 3 serious events

Other events: 10 other events

Deaths: 5 deaths

Cohort C

Serious events: 5 serious events

Other events: 7 other events

Deaths: 0 deaths

Group 1

Serious events: 11 serious events

Other events: 46 other events

Deaths: 20 deaths

Group 2

Serious events: 5 serious events

Other events: 33 other events

Deaths: 11 deaths

Serious adverse events

Measure	Cohort A n=8 participants at risk Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=10 participants at risk Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C n=7 participants at risk Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken ora	Group 1 n=46 participants at risk Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Group 2 n=33 participants at risk Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Blood and lymphatic system disorders Anaemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Blood and lymphatic system disorders Febrile neutropenia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Blood and lymphatic system disorders Neutropenia	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Cardiac disorders Acute coronary syndrome	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Cardiac disorders Atrial fibrillation	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Cardiac disorders Cardiac failure	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Cardiac disorders Cardiac tamponade	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Diarrhoea	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Intestinal obstruction	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Nausea	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Pneumatosis intestinalis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Stomatitis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Vomiting	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Asthenia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Chest pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Chills	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Malaise	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Oedema peripheral	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Pyrexia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Diverticulitis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Peritonitis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Pneumonia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Post procedural infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Pyelonephritis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Sepsis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Tracheobronchitis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Upper respiratory tract infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood bilirubin increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Neutrophil count decreased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Nervous system disorders Headache	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Nervous system disorders Syncope	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Psychiatric disorders Depression	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Psychiatric disorders Mental status changes	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Renal and urinary disorders Acute kidney injury	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Vascular disorders Hypertension	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Vascular disorders Hypotension	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Vascular disorders Peripheral ischaemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks

Other adverse events

Measure	Cohort A n=8 participants at risk Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B	Cohort B n=10 participants at risk Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Cohort C n=7 participants at risk Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken ora	Group 1 n=46 participants at risk Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally	Group 2 n=33 participants at risk Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally
Investigations Platelet count decreased	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.9% 5/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Skin mass	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Blood and lymphatic system disorders Anaemia	37.5% 3/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	30.0% 3/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	85.7% 6/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	26.1% 12/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	21.2% 7/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Blood and lymphatic system disorders Leukopenia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Blood and lymphatic system disorders Lymphopenia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Blood and lymphatic system disorders Neutropenia	62.5% 5/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	70.0% 7/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	71.4% 5/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	43.5% 20/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	27.3% 9/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Blood and lymphatic system disorders Thrombocytopenia	37.5% 3/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	32.6% 15/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	24.2% 8/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Cardiac disorders Pericardial effusion	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Cardiac disorders Tachycardia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Ear and labyrinth disorders Tinnitus	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Eye disorders Eye oedema	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Eye disorders Eye pruritus	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Eye disorders Lacrimation increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Eye disorders Ocular hyperaemia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Eye disorders Vision blurred	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Abdominal pain	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Abdominal pain upper	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Ascites	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Constipation	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.9% 5/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Diarrhoea	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	37.0% 17/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	24.2% 8/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Diverticulum	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Dry mouth	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	18.2% 6/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Dyspepsia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Dysphagia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Flatulence	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.9% 5/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Gingival pain	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Large intestinal stenosis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Nausea	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	50.0% 5/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	37.0% 17/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	33.3% 11/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Paraesthesia oral	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Stomatitis	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	40.0% 4/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	52.2% 24/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	33.3% 11/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Toothache	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Gastrointestinal disorders Vomiting	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	13.0% 6/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	21.2% 7/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Asthenia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Axillary pain	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Chest discomfort	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Chills	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Fatigue	50.0% 4/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	71.4% 5/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	41.3% 19/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	30.3% 10/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Influenza like illness	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Mucosal inflammation	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Non-cardiac chest pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Oedema peripheral	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	85.7% 6/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	21.7% 10/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	24.2% 8/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
General disorders Pyrexia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	21.7% 10/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	15.2% 5/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Immune system disorders Seasonal allergy	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Bronchitis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Ear infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Fungal infection	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Groin infection	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Herpes zoster	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Hordeolum	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Influenza	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Kidney infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Nail bed infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Nail infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Nasopharyngitis	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Onychomycosis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Oral herpes	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Pneumonia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Rash pustular	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Respiratory tract infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Sinusitis	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	13.0% 6/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Tooth infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Upper respiratory tract infection	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	17.4% 8/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Infections and infestations Urinary tract infection	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	17.4% 8/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Injury, poisoning and procedural complications Fall	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Injury, poisoning and procedural complications Ligament sprain	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Injury, poisoning and procedural complications Limb injury	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Injury, poisoning and procedural complications Skin laceration	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Alanine aminotransferase decreased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Alanine aminotransferase increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	17.4% 8/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	15.2% 5/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Amylase increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Aspartate aminotransferase decreased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Aspartate aminotransferase increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	26.1% 12/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	21.2% 7/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood alkaline phosphatase increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood cholesterol increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood creatine phosphokinase increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood creatinine increased	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood folate decreased	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood glucose increased	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood lactate dehydrogenase increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Blood triglycerides increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Gamma-glutamyltransferase increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.9% 5/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations High density lipoprotein decreased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations High density lipoprotein increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Lipase decreased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Lipase increased	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Low density lipoprotein increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Neutrophil count decreased	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	34.8% 16/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	30.3% 10/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Platelet count increased	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Prothrombin time prolonged	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations Weight decreased	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	13.0% 6/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Investigations White blood cell count decreased	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	30.0% 3/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.3% 13/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	18.2% 6/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Decreased appetite	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	13.0% 6/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hyperglycaemia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	13.0% 6/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	24.2% 8/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypermagnesaemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypoalbuminaemia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	57.1% 4/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypokalaemia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	71.4% 5/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	19.6% 9/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypomagnesaemia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hyponatraemia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Metabolism and nutrition disorders Hypophosphataemia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	71.4% 5/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	17.4% 8/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	18.2% 6/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.3% 13/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	15.2% 5/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	19.6% 9/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Coccydynia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Joint stiffness	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Limb mass	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.9% 5/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Neck pain	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.9% 5/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Nervous system disorders Dizziness	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Nervous system disorders Dysgeusia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	23.9% 11/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Nervous system disorders Headache	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	15.2% 7/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	27.3% 9/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Nervous system disorders Neuropathy peripheral	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Nervous system disorders Paraesthesia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Psychiatric disorders Agitation	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Psychiatric disorders Anxiety	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Psychiatric disorders Insomnia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	15.2% 7/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	15.2% 5/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Renal and urinary disorders Micturition urgency	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Renal and urinary disorders Pollakiuria	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Renal and urinary disorders Proteinuria	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Reproductive system and breast disorders Breast pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Bronchiectasis	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Cough	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	21.7% 10/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	24.2% 8/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	42.9% 3/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.9% 5/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	15.2% 5/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	13.0% 6/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Hypoxia	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	20.0% 2/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Nasal dryness	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	2.2% 1/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Pneumonitis	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	15.2% 7/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Respiratory symptom	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.5% 3/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Onychomadesis	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Pruritus	37.5% 3/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	28.6% 2/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Rash	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	50.0% 5/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	71.4% 5/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	17.4% 8/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	18.2% 6/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Rash maculo-papular	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	12.1% 4/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Skin and subcutaneous tissue disorders Urticaria	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Vascular disorders Hot flush	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	13.0% 6/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	9.1% 3/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Vascular disorders Hypertension	0.00% 0/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	14.3% 1/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	8.7% 4/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Vascular disorders Hypotension	25.0% 2/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	3.0% 1/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks
Vascular disorders Lymphoedema	12.5% 1/8 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	10.0% 1/10 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	0.00% 0/7 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	4.3% 2/46 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks	6.1% 2/33 • Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 108 weeks

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER