Trial Outcomes & Findings for A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (NCT NCT04975308)

NCT ID: NCT04975308

Last Updated: 2025-07-11

Results Overview

PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 874 participants
• Primary outcome timeframe: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)
• Results posted on: 2025-07-11

Participant Flow

The study was initially planned with participants randomized 1:1 to either arm A or arm B. Following a protocol amendment, arm C was added later, after randomization to arms A and B had already begun.

Participant milestones

Measure	Arm A: Imlunestrant Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.	Arm C: Imlunestrant + Abemaciclib Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met.
Overall Study STARTED	331	330	213
Overall Study Analysis Population for the Comparison Between Arm A and Arm B	331	330	0
Overall Study Analysis Population for the Comparison Between Arm C and Arm A	213	0	213
Overall Study Estrogen Receptor 1 (ESR1) Mutation-Detected Population for Comparison Between Arm A and Arm B	138	118	0
Overall Study Received at Least 1 Dose of Study Drug	326	324	209
Overall Study Safety Analysis Population	327	324	208
Overall Study COMPLETED	246	264	117
Overall Study NOT COMPLETED	85	66	96

Reasons for withdrawal

Measure	Arm A: Imlunestrant Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.	Arm C: Imlunestrant + Abemaciclib Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met.
Overall Study Withdrawal by Subject	6	16	6
Overall Study Physician Decision	0	3	1
Overall Study Adverse Event	10	1	12
Overall Study On study treatment (Ongoing)	65	43	75
Overall Study Protocol Deviation	4	3	2

Baseline Characteristics

A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer

Baseline characteristics by cohort

Measure	Imlunestrant n=331 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Investigator's Choice of Endocrine Therapy n=330 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.	Imlunestrant + Abemaciclib n=213 Participants Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met.	Total n=874 Participants Total of all reporting groups
Age, Continuous	60.4 years STANDARD_DEVIATION 11.6 • n=5 Participants	60.8 years STANDARD_DEVIATION 12.0 • n=7 Participants	61.9 years STANDARD_DEVIATION 11.1 • n=5 Participants	60.9 years STANDARD_DEVIATION 11.6 • n=4 Participants
Sex: Female, Male Female	327 Participants n=5 Participants	329 Participants n=7 Participants	211 Participants n=5 Participants	867 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	79 Participants n=5 Participants	80 Participants n=7 Participants	37 Participants n=5 Participants	196 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	218 Participants n=5 Participants	216 Participants n=7 Participants	148 Participants n=5 Participants	582 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	34 Participants n=5 Participants	34 Participants n=7 Participants	28 Participants n=5 Participants	96 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	23 Participants n=5 Participants	16 Participants n=7 Participants	3 Participants n=5 Participants	42 Participants n=4 Participants
Race (NIH/OMB) Asian	92 Participants n=5 Participants	96 Participants n=7 Participants	72 Participants n=5 Participants	260 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	26 Participants n=4 Participants
Race (NIH/OMB) White	186 Participants n=5 Participants	191 Participants n=7 Participants	111 Participants n=5 Participants	488 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants	13 Participants n=7 Participants	16 Participants n=5 Participants	46 Participants n=4 Participants
Estrogen Receptor 1 (ESR1)-Mutation Detected	138 Participants n=5 Participants	118 Participants n=7 Participants	67 Participants n=5 Participants	323 Participants n=4 Participants
Estrogen Receptor 1 (ESR1)-Mutation Not detected	193 Participants n=5 Participants	212 Participants n=7 Participants	146 Participants n=5 Participants	551 Participants n=4 Participants

PRIMARY outcome

Timeframe: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)

Population: All participants who were randomly assigned to either arm A or arm B (including censored). Number of participants censored in "Arm A=94," "Arm B=77."

PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=331 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=330 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Investigator-assessed Progression Free Survival (PFS) (Between Arm A and Arm B)	5.55 Months Interval 5.32 to 7.26	5.52 Months Interval 4.6 to 5.62

PRIMARY outcome

Timeframe: Randomization to the date of first documented progression of disease or death from any cause (up to 26 months)

Population: All participants who were randomly assigned to either arm A or arm C concurrently (including censored). Number of participants censored in "Arm C=99," "Arm A=64."

PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=213 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=213 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Investigator-assessed PFS (Between Arm C and Arm A)	9.36 Months Interval 7.49 to 11.86	5.49 Months Interval 3.78 to 5.62

PRIMARY outcome

Timeframe: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)

Population: All participants who were randomly assigned to either arm A or arm B and had ESR1 mutations detected at baseline (including censored). Number of participants censored in "Arm A=29," "Arm B=16."

PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=138 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=118 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Investigator-assessed PFS in the Estrogen Receptor 1 (ESR1)-Mutation Detected Population (Between Arm A and Arm B)	5.49 Months Interval 3.91 to 7.39	3.84 Months Interval 3.68 to 5.52

SECONDARY outcome

Timeframe: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)

Population: All participants who were randomly assigned to either arm A or arm B (including censored). Number of participants censored in "Arm A=171," "Arm B=171."

PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=331 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=330 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm A and Arm B)	9.23 Months Interval 7.33 to 11.07	7.36 Months Interval 5.55 to 9.4

SECONDARY outcome

Timeframe: Randomization to the date of first documented progression of disease or death from any cause (up to 25 months)

Population: All participants who were randomly assigned to either arm A or arm C concurrently (including censored). Number of participants censored in "Arm C=132," "Arm A=116."

PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=213 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=213 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm C and Arm A)	14.52 Months Interval 11.37 to Due to the high number of censored participants, there were not enough events to estimate the upper limit of the 95% confidence interval.	9.23 Months Interval 5.49 to 13.7

SECONDARY outcome

Timeframe: Randomization until measured progressive disease (up to 28 months)

Population: All participants who were randomly assigned to either arm A or arm B.

ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

Outcome measures

Measure	Arm A: Imlunestrant n=331 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=330 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm A and Arm B)	10.3 Percentage of participants Interval 7.0 to 13.5	6.4 Percentage of participants Interval 3.7 to 9.0

SECONDARY outcome

Timeframe: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 26 Months)

Population: All participants who were randomly assigned to either arm A or arm B and had achieved CR or PR responses (including censored). Number of participants censored in "Arm A=17," "Arm B=7."

DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=34 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=21 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Investigator-assessed Duration of Response (DoR) (Between Arm A and Arm B)	11.10 Months Interval 7.43 to 23.92	7.39 Months Interval 5.59 to 15.67

SECONDARY outcome

Timeframe: Randomization until measured progressive disease (up to 28 months)

Population: All participants who were randomly assigned to either arm A or arm B.

CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Arm A: Imlunestrant n=331 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=330 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm A and Arm B)	46.8 Percentage of participants Interval 41.5 to 52.2	45.5 Percentage of participants Interval 40.1 to 50.8

SECONDARY outcome

Timeframe: Randomization until measured progressive disease (up to 26 months)

Population: All participants who were randomly assigned to either arm A or arm C concurrently.

ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

Outcome measures

Measure	Arm A: Imlunestrant n=213 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=213 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm C and Arm A)	21.1 Percentage of participants Interval 15.6 to 26.6	9.4 Percentage of participants Interval 5.5 to 13.3

SECONDARY outcome

Timeframe: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 19 Months)

Population: All participants who were randomly assigned to either arm C or arm A and had achieved CR or PR responses (including censored). Number of participants censored in "Arm C=30," "Arm A=11."

DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=45 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=20 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Investigator-assessed Duration of Response (DoR) (Between Arm C and Arm A)	11.07 Months Interval 9.13 to Due to the high number of censored participants, there were not enough events to estimate the upper limit of the 95% confidence interval.	10.02 Months Interval 6.57 to 15.01

SECONDARY outcome

Timeframe: Randomization until measured progressive disease (up to 26 months)

Population: All participants who were randomly assigned to either arm A or arm C concurrently.

CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Arm A: Imlunestrant n=213 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=213 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm C and Arm A)	62.9 Percentage of participants Interval 56.4 to 69.4	44.1 Percentage of participants Interval 37.5 to 50.8

SECONDARY outcome

Timeframe: Randomization through follow-up (up to 24 months)

Population: All participants who were randomly assigned to either arm A or arm B and had at least one NRS assessment available (including censored). Number of participants censored in "Arm A=258," "Arm B=267."

Time to sustained worsening of worst pain is defined as the time from randomization to the first increase (≥2 points) in the weekly average of the worst pain score, with confirmation in the next consecutive week. It was measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single-item, participant-administered, 11-point horizontal scale ranging from 0 to 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine." Participants not known to have sustained worsening will be censored at the last documented assessment.

Outcome measures

Measure	Arm A: Imlunestrant n=313 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=317 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm A and Arm B)	NA Months Due to the high number of censored participants, there were not enough events to estimate the median and 95% confidence interval.	NA Months Due to the high number of censored participants, there were not enough events to estimate the median and 95% confidence interval.

SECONDARY outcome

Timeframe: Randomization through follow-up (up to 20 months)

Population: All participants who were randomly assigned to either arm A or arm C concurrently and had at least one NRS assessment available (including censored). Number of participants censored in "Arm C=163," "Arm A=162."

Time to sustained worsening of worst pain is defined as the time from randomization to the first increase (≥2 points) in the weekly average of the worst pain score, with confirmation in the next consecutive week. It was measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single-item, participant-administered, 11-point horizontal scale ranging from 0 to 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine." Participants not known to have sustained worsening will be censored at the last documented assessment.

Outcome measures

Measure	Arm A: Imlunestrant n=204 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=198 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm C and Arm A)	NA Months Due to the high number of censored participants, there were not enough events to estimate the median and 95% confidence interval.	NA Months Due to the high number of censored participants, there were not enough events to estimate the median and 95% confidence interval.

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (within 2 to 4 hours post-dose), Cycle 2 Day 1 (Predose), Cycle 3 Day 1 (3 hours post-dose, 5 hours post-dose), Cycle 4 Day 1 (Predose)

Population: All randomised participants who received at least 1 dose of study drug and had evaluable PK data for this outcome.

• Sampling timepoints for PK outcome analysis were relative to Imlunestrant dosing.
• For Cycle 1 Day 1, sampling occurred at a "single" timepoint within the 2- to 4-hour window after Imlunestrant dosing, with the timepoint varying across analyzed participants.

Outcome measures

Measure	Arm A: Imlunestrant n=276 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=189 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Pharmacokinetics (PK): Plasma Concentration of Imlunestrant Cycle 1 Day 1 (within 2 to 4 hours postdose)	45.7 nanograms per milliliter Geometric Coefficient of Variation 123	56.5 nanograms per milliliter Geometric Coefficient of Variation 122
Pharmacokinetics (PK): Plasma Concentration of Imlunestrant Cycle 2 Day 1 (Predose)	76 nanograms per milliliter Geometric Coefficient of Variation 76	64.9 nanograms per milliliter Geometric Coefficient of Variation 103
Pharmacokinetics (PK): Plasma Concentration of Imlunestrant Cycle 3 Day 1 (3 hours post-dose)	141 nanograms per milliliter Geometric Coefficient of Variation 70	144 nanograms per milliliter Geometric Coefficient of Variation 73
Pharmacokinetics (PK): Plasma Concentration of Imlunestrant Cycle 3 Day 1 (5 hours post-dose)	136 nanograms per milliliter Geometric Coefficient of Variation 69	146 nanograms per milliliter Geometric Coefficient of Variation 69
Pharmacokinetics (PK): Plasma Concentration of Imlunestrant Cycle 4 Day 1 (Predose)	85.2 nanograms per milliliter Geometric Coefficient of Variation 69	63 nanograms per milliliter Geometric Coefficient of Variation 97

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (within 2 to 4 hours post-dose), Cycle 2 Day 1 (Predose), Cycle 3 Day 1 (3 hours post-dose, 5 hours post-dose), Cycle 4 Day 1 (Predose)

Population: All randomised participants who received at least 1 dose of study drug and had evaluable PK data for this outcome.

• Plasma concentration of total abemaciclib is the concentration of the parent abemaciclib and its metabolites in the plasma.
• Sampling timepoints for PK outcome analysis were relative to Imlunestrant dosing.
• For Cycle 1 Day 1, sampling occurred at a "single" timepoint within the 2- to 4-hour window after Imlunestrant dosing, with the timepoint varying across analyzed participants.

Outcome measures

Measure	Arm A: Imlunestrant n=176 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib Cycle 3 Day 1 (5 hours post-dose)	926 nanograms per milliliter Geometric Coefficient of Variation 64	—
Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib Cycle 1 Day 1 (within 2 to 4 hours postdose)	158 nanograms per milliliter Geometric Coefficient of Variation 120	—
Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib Cycle 2 Day 1 (Predose)	792 nanograms per milliliter Geometric Coefficient of Variation 82	—
Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib Cycle 3 Day 1 (3 hours post-dose)	880 nanograms per milliliter Geometric Coefficient of Variation 74	—
Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib Cycle 4 Day 1 (Predose)	783 nanograms per milliliter Geometric Coefficient of Variation 59	—

SECONDARY outcome

Timeframe: Randomization until death from any cause (estimated as up to 5 years)

OS in the ITT population

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization until death from any cause (estimated as up to 5 years)

OS in the ESR1-mutation detected population

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)

Population: All participants who were randomly assigned to either arm A or arm B and had ESR1 mutations detected at baseline (including censored). Number of participants censored in "Arm A=64," "Arm B=47."

PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=138 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=118 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Blinded Independent Review Committee (BIRC) Assessed PFS in the ESR1-Mutation Detected Population (Between Arm A and Arm B)	7.43 Months Interval 4.83 to 11.07	5.49 Months Interval 3.84 to 6.7

SECONDARY outcome

Timeframe: Randomization until measured progressive disease (up to 28 months)

Population: All participants who were randomly assigned to either arm A or arm B and had ESR1 mutations detected at baseline.

ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

Outcome measures

Measure	Arm A: Imlunestrant n=138 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=118 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)	11.6 Percentage of participants Interval 6.3 to 16.9	5.9 Percentage of participants Interval 1.7 to 10.2

SECONDARY outcome

Timeframe: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)

Population: All participants who were randomly assigned to either arm A or arm B, had ESR1 mutations detected at baseline and had achieved CR or PR responses (including censored). Number of participants censored in "Arm A=5," "Arm B=0."

DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).

Outcome measures

Measure	Arm A: Imlunestrant n=16 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=7 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Investigator-assessed Duration of Response (DoR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)	10.02 Months Interval 3.98 to 14.59	5.59 Months Interval 2.92 to 7.79

SECONDARY outcome

Timeframe: Randomization until measured progressive disease (up to 28 months)

Population: All participants who were randomly assigned to either arm A or arm B and had ESR1 mutations detected at baseline.

CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Arm A: Imlunestrant n=138 Participants Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy n=118 Participants Participants received the investigator's choice of endocrine therapy, either exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle, or Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)	46.4 Percentage of participants Interval 38.1 to 54.7	36.4 Percentage of participants Interval 27.8 to 45.1

Adverse Events

Arm A: Imlunestrant

Serious events: 46 serious events

Other events: 250 other events

Deaths: 62 deaths

Arm B: Investigator's Choice of Endocrine Therapy - Exemestane

Serious events: 6 serious events

Other events: 26 other events

Deaths: 8 deaths

Arm B: Investigator's Choice of Endocrine Therapy - Fulvestrant

Serious events: 49 serious events

Other events: 229 other events

Deaths: 82 deaths

Arm C: Imlunestrant + Abemaciclib

Serious events: 42 serious events

Other events: 203 other events

Deaths: 36 deaths

Serious adverse events

Measure	Arm A: Imlunestrant n=327 participants at risk Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy - Exemestane n=32 participants at risk This group includes Arm B participants for whom the Investigator's Choice of Endocrine Therapy was Exemestane. Participants received exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle until disease progression or a criterion for discontinuation was met.	Arm B: Investigator's Choice of Endocrine Therapy - Fulvestrant n=292 participants at risk This group includes Arm B participants for whom the Investigator's Choice of Endocrine Therapy was Fulvestrant. Participants received Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.	Arm C: Imlunestrant + Abemaciclib n=208 participants at risk Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met.
Blood and lymphatic system disorders Anaemia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.96% 2/208 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Cytopenia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Febrile bone marrow aplasia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Febrile neutropenia	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Pancytopenia	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Thrombocytopenia	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Acute myocardial infarction	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Atrial fibrillation	0.61% 2/327 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Cardiac arrest	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Cardiac failure	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Myocardial infarction	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Right ventricular failure	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Sinus tachycardia	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Stress cardiomyopathy	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Cardiac disorders Supraventricular tachycardia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Ear and labyrinth disorders Vertigo positional	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Endocrine disorders Hyperthyroidism	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Eye disorders Conjunctival papillae	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Abdominal distension	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Abdominal pain	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.96% 2/208 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Abdominal pain upper	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Ascites	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Colitis	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Constipation	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Diarrhoea	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.4% 3/208 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Enterocolitis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Gastrointestinal haemorrhage	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Haemorrhoids	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Ileus	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Intestinal obstruction	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Nausea	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Oesophagitis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 4 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Vomiting	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.96% 2/208 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Asthenia	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Chest pain	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Chills	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Death	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders General physical health deterioration	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Mucosal inflammation	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Pyrexia	0.61% 2/327 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.0% 3/292 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Hepatobiliary disorders Bile duct stone	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Hepatobiliary disorders Cholecystitis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Hepatobiliary disorders Hepatotoxicity	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Abdominal infection	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Appendicitis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Appendicitis perforated	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Campylobacter colitis	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Cellulitis	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Clostridial infection	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Clostridium difficile infection	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Covid-19	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Covid-19 pneumonia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Dengue fever	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Device related infection	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Diverticulitis	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Empyema	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Gastroenteritis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Gastroenteritis viral	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Herpes simplex encephalitis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Herpes zoster	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Infection	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Kidney infection	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Klebsiella bacteraemia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Laryngitis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Osteomyelitis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Otitis media	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Paronychia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Pneumonia	0.61% 2/327 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.0% 3/292 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.9% 4/208 • Number of events 4 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Respiratory tract infection	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Sepsis	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.0% 3/292 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.96% 2/208 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Septic shock	0.61% 2/327 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Upper respiratory tract infection	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Urinary tract infection	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Wound infection	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Craniocerebral injury	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Femur fracture	0.31% 1/327 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Fractured sacrum	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Radius fracture	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Ureteric injury	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Blood calcium increased	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Blood creatinine increased	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Platelet count decreased	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Metabolism and nutrition disorders Hypernatraemia	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.96% 2/208 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 4 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Neck pain	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.96% 2/208 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Rheumatic disorder	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Bell's palsy	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Cerebellar infarction	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Cerebral infarction	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Dizziness	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Hemiparesis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Lethargy	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Neuropathy peripheral	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Peripheral motor neuropathy	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Spinal cord compression	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Transient ischaemic attack	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Trigeminal neuralgia	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Psychiatric disorders Panic reaction	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Renal and urinary disorders Acute kidney injury	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.68% 2/292 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Renal and urinary disorders Chronic kidney disease	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Renal and urinary disorders Hydronephrosis	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Renal and urinary disorders Nephrolithiasis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Renal and urinary disorders Renal failure	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.96% 2/208 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Renal and urinary disorders Urinary tract obstruction	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 4/327 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.61% 2/327 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Surgical and medical procedures Wound treatment	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Vascular disorders Deep vein thrombosis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Vascular disorders Hypovolaemic shock	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Vascular disorders Lymphoedema	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Vascular disorders Peripheral artery thrombosis	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Vascular disorders Superior vena cava syndrome	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.48% 1/208 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Vascular disorders Thrombosis	0.31% 1/327 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."

Other adverse events

Measure	Arm A: Imlunestrant n=327 participants at risk Participants received Imlunestrant 400 milligrams (mg) orally once daily on days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation were met.	Arm B: Investigator's Choice of Endocrine Therapy - Exemestane n=32 participants at risk This group includes Arm B participants for whom the Investigator's Choice of Endocrine Therapy was Exemestane. Participants received exemestane 25 mg administered orally once daily on days 1 to 28 of a 28-day cycle until disease progression or a criterion for discontinuation was met.	Arm B: Investigator's Choice of Endocrine Therapy - Fulvestrant n=292 participants at risk This group includes Arm B participants for whom the Investigator's Choice of Endocrine Therapy was Fulvestrant. Participants received Fulvestrant 500 mg intramuscularly on days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond, until disease progression or a criterion for discontinuation was met.	Arm C: Imlunestrant + Abemaciclib n=208 participants at risk Participants received Imlunestrant 400 mg orally once daily on Days 1 to 28 of a 28-day cycle, plus Abemaciclib 150 mg orally twice daily on Days 1 to 28 of a 28-day cycle, until disease progression or a criterion for discontinuation was met.
General disorders Asthenia	10.1% 33/327 • Number of events 39 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	15.6% 5/32 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	7.2% 21/292 • Number of events 23 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	16.8% 35/208 • Number of events 46 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Fatigue	13.8% 45/327 • Number of events 48 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.5% 19/292 • Number of events 19 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	22.1% 46/208 • Number of events 59 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Anaemia	11.6% 38/327 • Number of events 52 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	25.0% 8/32 • Number of events 11 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	15.4% 45/292 • Number of events 62 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	43.8% 91/208 • Number of events 128 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Leukopenia	2.1% 7/327 • Number of events 11 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	2.4% 7/292 • Number of events 13 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	10.6% 22/208 • Number of events 32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Neutropenia	3.1% 10/327 • Number of events 13 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.7% 5/292 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	26.4% 55/208 • Number of events 111 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Blood and lymphatic system disorders Thrombocytopenia	1.8% 6/327 • Number of events 8 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	2.7% 8/292 • Number of events 8 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.6% 20/208 • Number of events 23 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Abdominal pain	6.1% 20/327 • Number of events 21 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.4% 10/292 • Number of events 12 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	12.5% 26/208 • Number of events 32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Abdominal pain upper	3.7% 12/327 • Number of events 14 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.7% 5/292 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	8.2% 17/208 • Number of events 21 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Constipation	10.7% 35/327 • Number of events 38 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.4% 3/32 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.5% 19/292 • Number of events 22 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	7.2% 15/208 • Number of events 16 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Diarrhoea	21.7% 71/327 • Number of events 101 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.4% 3/32 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	12.7% 37/292 • Number of events 41 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	86.5% 180/208 • Number of events 372 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Nausea	18.0% 59/327 • Number of events 74 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	12.5% 4/32 • Number of events 4 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	13.4% 39/292 • Number of events 45 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	50.0% 104/208 • Number of events 144 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Gastrointestinal disorders Vomiting	9.5% 31/327 • Number of events 44 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.1% 15/292 • Number of events 17 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	31.7% 66/208 • Number of events 112 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Injection site pain	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.5% 19/292 • Number of events 21 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Oedema peripheral	3.4% 11/327 • Number of events 15 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	2.7% 8/292 • Number of events 10 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 13/208 • Number of events 13 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
General disorders Pyrexia	4.9% 16/327 • Number of events 20 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.4% 10/292 • Number of events 10 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.7% 14/208 • Number of events 20 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Covid-19	6.7% 22/327 • Number of events 24 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	7.5% 22/292 • Number of events 23 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.3% 11/208 • Number of events 11 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Nasopharyngitis	2.1% 7/327 • Number of events 10 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 9/292 • Number of events 10 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.8% 8/208 • Number of events 8 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Infections and infestations Urinary tract infection	3.4% 11/327 • Number of events 15 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	7.2% 21/292 • Number of events 24 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	4.8% 10/208 • Number of events 12 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/327 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/292 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Alanine aminotransferase increased	12.5% 41/327 • Number of events 53 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	14.7% 43/292 • Number of events 64 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	16.8% 35/208 • Number of events 49 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Aspartate aminotransferase increased	14.4% 47/327 • Number of events 59 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.4% 3/32 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	15.8% 46/292 • Number of events 65 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	20.7% 43/208 • Number of events 55 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Blood alkaline phosphatase increased	9.2% 30/327 • Number of events 41 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	11.0% 32/292 • Number of events 47 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.7% 14/208 • Number of events 18 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Blood creatinine increased	3.4% 11/327 • Number of events 20 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	2.4% 7/292 • Number of events 10 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	21.2% 44/208 • Number of events 66 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Gamma-glutamyltransferase increased	5.2% 17/327 • Number of events 23 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	7.9% 23/292 • Number of events 28 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	2.4% 5/208 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Lymphocyte count decreased	4.6% 15/327 • Number of events 27 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.8% 20/292 • Number of events 34 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	4.3% 9/208 • Number of events 11 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Neutrophil count decreased	3.1% 10/327 • Number of events 20 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.1% 15/292 • Number of events 23 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	22.6% 47/208 • Number of events 89 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Platelet count decreased	3.7% 12/327 • Number of events 22 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.4% 10/292 • Number of events 17 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	8.7% 18/208 • Number of events 21 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations Weight decreased	3.7% 12/327 • Number of events 13 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.1% 15/292 • Number of events 17 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.7% 14/208 • Number of events 16 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Investigations White blood cell count decreased	4.3% 14/327 • Number of events 28 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.8% 17/292 • Number of events 26 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	15.9% 33/208 • Number of events 67 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Metabolism and nutrition disorders Decreased appetite	8.0% 26/327 • Number of events 31 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	4.8% 14/292 • Number of events 15 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	20.2% 42/208 • Number of events 53 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Metabolism and nutrition disorders Hyperglycaemia	5.5% 18/327 • Number of events 25 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	7.2% 21/292 • Number of events 29 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	2.9% 6/208 • Number of events 6 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Metabolism and nutrition disorders Hypokalaemia	1.2% 4/327 • Number of events 4 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.7% 5/292 • Number of events 7 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.1% 19/208 • Number of events 29 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Arthralgia	15.3% 50/327 • Number of events 65 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	12.5% 4/32 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	14.7% 43/292 • Number of events 57 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.6% 20/208 • Number of events 20 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Back pain	11.6% 38/327 • Number of events 47 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	8.9% 26/292 • Number of events 30 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.8% 12/208 • Number of events 13 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Bone pain	4.0% 13/327 • Number of events 13 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.4% 3/32 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.4% 10/292 • Number of events 11 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.9% 4/208 • Number of events 4 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Osteoporosis	0.61% 2/327 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.34% 1/292 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Musculoskeletal and connective tissue disorders Pain in extremity	4.9% 16/327 • Number of events 19 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.4% 3/32 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	7.5% 22/292 • Number of events 24 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	4.3% 9/208 • Number of events 11 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Dizziness	3.1% 10/327 • Number of events 11 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 9/292 • Number of events 9 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.8% 12/208 • Number of events 14 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Headache	8.6% 28/327 • Number of events 30 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 3 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.2% 27/292 • Number of events 28 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	9.6% 20/208 • Number of events 25 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Nervous system disorders Neuropathy peripheral	2.1% 7/327 • Number of events 8 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.4% 4/292 • Number of events 4 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/208 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Respiratory, thoracic and mediastinal disorders Cough	8.9% 29/327 • Number of events 35 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.5% 19/292 • Number of events 21 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	8.7% 18/208 • Number of events 21 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.3% 24/327 • Number of events 25 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	4.5% 13/292 • Number of events 15 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	4.3% 9/208 • Number of events 9 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Skin and subcutaneous tissue disorders Alopecia	2.1% 7/327 • Number of events 7 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	0.00% 0/32 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	1.7% 5/292 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.8% 12/208 • Number of events 12 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Skin and subcutaneous tissue disorders Rash	1.5% 5/327 • Number of events 5 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.2% 2/32 • Number of events 2 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	2.7% 8/292 • Number of events 10 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	4.8% 10/208 • Number of events 10 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."
Vascular disorders Hot flush	6.7% 22/327 • Number of events 22 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	3.1% 1/32 • Number of events 1 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	6.8% 20/292 • Number of events 20 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."	5.3% 11/208 • Number of events 11 • Baseline up to 28 months Adverse events were reported for the "Safety Analysis Population."

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800- 545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60