Trial Outcomes & Findings for A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer) (NCT NCT05288166)

Last Updated: 2025-06-27

Results Overview

The rPFS time is measured from the date of randomization to the earliest date of investigator determined radiographic disease progression (by objective radiographic disease assessment per response evaluation criteria in solid tumors (RECIST) version 1.1 for soft tissue AND/OR radionuclide bone scan using prostate cancer working group 3 -PCWG3 criteria for bone) or death from any cause, whichever occurs first.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

925 participants

Primary outcome timeframe

From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 months)

Results posted on

2025-06-27

Participant Flow

Completers included participants who had an event (radiographic progression or death) and participants who were off the treatment and were alive at study conclusion.

Participant milestones

Participant milestones
Measure	Abemaciclib Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Overall Study STARTED	463	462
Overall Study Received at Least One Dose of Study Drug	460	460
Overall Study COMPLETED	47	39
Overall Study NOT COMPLETED	416	423

Reasons for withdrawal

Reasons for withdrawal
Measure	Abemaciclib Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	2	0
Overall Study Physician Decision	0	2
Overall Study Screen Failure	1	1
Overall Study Withdrawal by Subject	4	2
Overall Study On Study Treatment	408	418

Baseline Characteristics

A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abemaciclib n=463 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=462 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Total n=925 Participants Total of all reporting groups
Age, Continuous	68.80 years STANDARD_DEVIATION 8.16 • n=5 Participants	69.30 years STANDARD_DEVIATION 8.07 • n=7 Participants	69.00 years STANDARD_DEVIATION 8.11 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	463 Participants n=5 Participants	462 Participants n=7 Participants	925 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	115 Participants n=5 Participants	126 Participants n=7 Participants	241 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	276 Participants n=5 Participants	271 Participants n=7 Participants	547 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	72 Participants n=5 Participants	65 Participants n=7 Participants	137 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Race (NIH/OMB) Asian	122 Participants n=5 Participants	120 Participants n=7 Participants	242 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) White	278 Participants n=5 Participants	286 Participants n=7 Participants	564 Participants n=5 Participants
Race (NIH/OMB) More than one race	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment Argentina	40 Participants n=5 Participants	39 Participants n=7 Participants	79 Participants n=5 Participants
Region of Enrollment Australia	28 Participants n=5 Participants	29 Participants n=7 Participants	57 Participants n=5 Participants
Region of Enrollment Belgium	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Brazil	46 Participants n=5 Participants	53 Participants n=7 Participants	99 Participants n=5 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment China	65 Participants n=5 Participants	70 Participants n=7 Participants	135 Participants n=5 Participants
Region of Enrollment Czechia	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment France	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment Germany	24 Participants n=5 Participants	22 Participants n=7 Participants	46 Participants n=5 Participants
Region of Enrollment Greece	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Hungary	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Israel	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Italy	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment Japan	39 Participants n=5 Participants	30 Participants n=7 Participants	69 Participants n=5 Participants
Region of Enrollment Mexico	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
Region of Enrollment Netherlands	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Poland	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment Romania	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment South Korea	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Spain	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Taiwan	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Turkey	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Region of Enrollment United Kingdom	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment United States	52 Participants n=5 Participants	67 Participants n=7 Participants	119 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 months)

Population: All randomized participants (including the censored participants). Number of participants censored in "Abemaciclib = 385," "Placebo = 389."

Outcome measures

Outcome measures
Measure	Abemaciclib n=463 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=462 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Radiographic Progression-Free Survival (rPFS) Assessed by Investigator	NA Months Due to high number of censored participants, the median, upper and lower limit 95% confidence interval were not estimable.	NA Months Due to high number of censored participants, the median, upper and lower limit 95% confidence interval were not estimable.

SECONDARY outcome

Timeframe: From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 months)

Population: All randomized participants (including the censored participants). Number of participants censored in "Abemaciclib = 435," "Placebo = 440"

Outcome measures

Outcome measures
Measure	Abemaciclib n=463 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=462 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Radiographic Progression-Free Survival (rPFS) Assessed by Blinded Independent Central Review (BICR)	NA Months Interval 11.11 to Due to high number of censored participants, the median, and upper limit of 95% confidence interval were not estimable.	NA Months Interval 13.02 to Due to high number of censored participants, the median, and upper limit of 95% confidence interval were not estimable.

SECONDARY outcome

Timeframe: Randomization to the earliest date of PSA or radiographic progression with a testosterone level of ≤50 ng/dL; or death from any cause (up to 22 months)

Population: All randomized participants (including the censored participants). Number of participants censored in "Abemaciclib = 363," "Placebo = 360."

CRPC-free survival is defined as the time from the date of randomization to the earliest date of castration resistance, as demonstrated by any of the following (whichever occurs earliest): Confirmed prostate-specific antigen (PSA) progression with serum testosterone ≤50 nanogram/deciliter (ng/dL) (≤1.73 nanomoles per liter(nmol/L)). Investigator-assessed radiographic progression with serum testosterone ≤50 ng/dL (≤1.73 nmol/L). Death from any cause.

Outcome measures

Outcome measures
Measure	Abemaciclib n=463 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=462 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Castration-resistant Prostate Cancer (CRPC)-Free Survival	NA Months Interval 14.86 to Due to high number of censored participants, the median, upper limit of 95% confidence interval was not estimable.	NA Months Due to high number of censored participants, the median, upper and lower limit 95% confidence interval were not estimable.

SECONDARY outcome

Timeframe: From Date of Randomization to Date of Death Due to Any Cause (Up to 22 Months)

Population: All randomized participants (including the censored participants). Number of participants censored in "Abemaciclib = 416," "Placebo = 430."

The OS time is measured from the date of randomization to the date of death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data were censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Abemaciclib n=463 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=462 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Overall Survival (OS)	NA Months Due to high number of censored participants, the median, upper and lower limit 95% confidence interval were not estimable.	NA Months Due to high number of censored participants, the median, upper and lower limit 95% confidence interval were not estimable.

SECONDARY outcome

Timeframe: Randomization to pain progression (up to 22 months)

Population: All randomized participants (including the censored participants). Number of participants censored in "Abemaciclib = 368," "Placebo = 343"

Outcome measures

Outcome measures
Measure	Abemaciclib n=463 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=462 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Time to Pain Progression	NA Months Due to high number of censored participants, the median, upper and lower limit of 95% confidence interval were not estimable.	19.13 Months Interval 15.35 to Due to high number of censored participants, the upper limit of 95% confidence interval was not estimable.

SECONDARY outcome

Timeframe: Randomization to the date of the first clinically meaningful HRQoL deterioration (up to 22 months)

Population: All randomized participants (including the censored participants). Number of participants censored in "Abemaciclib = 328," "Placebo = 394"

Time to deterioration in health-related quality of life (HRQoL) was defined as the time from randomization to the date of the first clinically meaningful HRQoL deterioration on 2 consecutive measurements. HRQoL evaluation was performed using the FACT-P questionnaire. Physical Well-Being subscale is a subsection of FACT-P questionnaire. FACT-P consists of 39 core items to assess health related quality of life in participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate cancer subscale (12 items). Each item is rated from 0 (Not at all) to 4 (Very much) and combined to produce subscale scores. FACT-P total score was the sum of all 5 subscale scores. It ranged from 0 to 156 with higher score indicating better quality of life. Physical well-being subscale score ranges from 0 to 28 with high score indicating better quality of life.

Outcome measures

Outcome measures
Measure	Abemaciclib n=463 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=462 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Time to Deterioration in Health-Related Quality of Life (HRQoL) Measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) - Physical Well-Being Subscale	NA Months Due to high number of censored participants, the median, upper and lower limit of 95% confidence interval were not estimable.	NA Months Due to high number of censored participants, the median, upper and lower limit of 95% confidence interval were not estimable.

SECONDARY outcome

Timeframe: Randomization to the date of the first clinically meaningful HRQoL deterioration (up to 22 months)

Population: All randomized participants (including the censored participants). Number of participants censored in "Abemaciclib = 329," "Placebo = 365."

Time to deterioration in health-related quality of life (HRQoL) was defined as the time from randomization to the date of the first clinically meaningful HRQoL deterioration on 2 consecutive measurements. HRQoL evaluation was performed using the FACT-P questionnaire. Prostate Cancer Subscale is a subsection of FACT-P questionnaire. FACT-P consists of 39 core items to assess health related quality of life in participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate cancer subscale (12 items). Each item is rated from 0 (Not at all) to 4 (Very much) and combined to produce subscale scores. FACT-P total score was the sum of all 5 subscale scores. It ranged from 0 to 156 with higher score indicating better quality of life. Prostate cancer subscale score ranges from 0 to 48 with high score indicating better quality of life.

Outcome measures

Outcome measures
Measure	Abemaciclib n=463 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=462 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Time to Deterioration in Health-Related Quality of Life (HRQoL) Measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) - Prostate Cancer Subscale	NA Months Due to high number of censored participants, the median, upper and lower limit of 95% confidence interval were not estimable.	NA Months Due to high number of censored participants, the median, upper and lower limit of 95% confidence interval were not estimable.

SECONDARY outcome

Timeframe: Predose on Cycle 1 Day 1, Predose and Predose on Cycle 2 Day 1 and Predose on Cycle 3 Day 1 (28 Day Cycles)

Population: All randomized participants who received at least one dose of study drug had evaluable PK data.

Maximum plasma concentration at steady state (Cmax,ss) of abemaciclib was evaluated.

Outcome measures

Outcome measures
Measure	Abemaciclib n=454 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib	308.3 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 50	—

Adverse Events

Abemaciclib

Serious events: 145 serious events

Other events: 445 other events

Deaths: 47 deaths

Placebo

Serious events: 68 serious events

Other events: 380 other events

Deaths: 32 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 08005455979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Abemaciclib n=460 participants at risk Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=460 participants at risk Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Blood and lymphatic system disorders Anaemia	54.8% 252/460 • Number of events 317 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	12.6% 58/460 • Number of events 72 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Blood and lymphatic system disorders Leukopenia	27.4% 126/460 • Number of events 259 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	2.2% 10/460 • Number of events 15 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Blood and lymphatic system disorders Lymphopenia	9.8% 45/460 • Number of events 84 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	4.3% 20/460 • Number of events 29 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Blood and lymphatic system disorders Neutropenia	47.2% 217/460 • Number of events 395 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	2.8% 13/460 • Number of events 18 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Blood and lymphatic system disorders Thrombocytopenia	27.2% 125/460 • Number of events 198 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	3.0% 14/460 • Number of events 20 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Gastrointestinal disorders Abdominal pain	15.9% 73/460 • Number of events 84 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	7.4% 34/460 • Number of events 40 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Gastrointestinal disorders Constipation	9.8% 45/460 • Number of events 53 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	9.3% 43/460 • Number of events 51 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Gastrointestinal disorders Diarrhoea	65.4% 301/460 • Number of events 636 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	13.5% 62/460 • Number of events 76 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Gastrointestinal disorders Nausea	25.2% 116/460 • Number of events 150 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	8.9% 41/460 • Number of events 48 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Gastrointestinal disorders Vomiting	14.1% 65/460 • Number of events 92 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	4.8% 22/460 • Number of events 25 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
General disorders Fatigue	38.7% 178/460 • Number of events 223 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	19.8% 91/460 • Number of events 102 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
General disorders Malaise	5.2% 24/460 • Number of events 29 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	1.7% 8/460 • Number of events 10 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
General disorders Oedema peripheral	14.3% 66/460 • Number of events 82 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	6.7% 31/460 • Number of events 40 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
General disorders Pyrexia	8.3% 38/460 • Number of events 45 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	3.0% 14/460 • Number of events 16 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Infections and infestations Covid-19	6.1% 28/460 • Number of events 29 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	4.6% 21/460 • Number of events 21 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Infections and infestations Urinary tract infection	9.8% 45/460 • Number of events 56 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	4.8% 22/460 • Number of events 27 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Investigations Alanine aminotransferase increased	13.7% 63/460 • Number of events 82 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	16.7% 77/460 • Number of events 93 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Investigations Aspartate aminotransferase increased	11.5% 53/460 • Number of events 68 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	15.2% 70/460 • Number of events 87 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Investigations Blood alkaline phosphatase increased	5.7% 26/460 • Number of events 30 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	3.3% 15/460 • Number of events 15 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Investigations Blood bilirubin increased	5.4% 25/460 • Number of events 35 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	6.1% 28/460 • Number of events 53 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Investigations Blood creatinine increased	28.3% 130/460 • Number of events 193 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	3.7% 17/460 • Number of events 22 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Investigations Weight decreased	7.0% 32/460 • Number of events 37 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	1.5% 7/460 • Number of events 7 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Metabolism and nutrition disorders Decreased appetite	18.9% 87/460 • Number of events 99 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	2.0% 9/460 • Number of events 10 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Metabolism and nutrition disorders Hypercholesterolaemia	5.4% 25/460 • Number of events 37 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	4.3% 20/460 • Number of events 25 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Metabolism and nutrition disorders Hyperglycaemia	3.0% 14/460 • Number of events 19 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	6.7% 31/460 • Number of events 35 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Metabolism and nutrition disorders Hypertriglyceridaemia	10.9% 50/460 • Number of events 62 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	10.2% 47/460 • Number of events 66 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Metabolism and nutrition disorders Hypoalbuminaemia	5.4% 25/460 • Number of events 43 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	3.0% 14/460 • Number of events 23 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Metabolism and nutrition disorders Hypokalaemia	28.9% 133/460 • Number of events 240 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	13.7% 63/460 • Number of events 106 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Musculoskeletal and connective tissue disorders Arthralgia	7.2% 33/460 • Number of events 36 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	8.5% 39/460 • Number of events 47 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Musculoskeletal and connective tissue disorders Back pain	5.9% 27/460 • Number of events 27 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	7.4% 34/460 • Number of events 43 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Musculoskeletal and connective tissue disorders Pain in extremity	3.7% 17/460 • Number of events 21 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	5.4% 25/460 • Number of events 31 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Nervous system disorders Dizziness	7.6% 35/460 • Number of events 43 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	5.2% 24/460 • Number of events 26 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Nervous system disorders Dysgeusia	8.0% 37/460 • Number of events 41 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	0.87% 4/460 • Number of events 4 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Nervous system disorders Headache	7.8% 36/460 • Number of events 40 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	7.4% 34/460 • Number of events 41 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Renal and urinary disorders Pollakiuria	5.2% 24/460 • Number of events 26 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	4.1% 19/460 • Number of events 27 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Respiratory, thoracic and mediastinal disorders Cough	8.7% 40/460 • Number of events 47 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	7.6% 35/460 • Number of events 43 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.2% 24/460 • Number of events 26 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	3.3% 15/460 • Number of events 17 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Skin and subcutaneous tissue disorders Rash	9.1% 42/460 • Number of events 46 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	3.9% 18/460 • Number of events 19 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Vascular disorders Hot flush	15.0% 69/460 • Number of events 74 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	21.3% 98/460 • Number of events 106 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.
Vascular disorders Hypertension	11.3% 52/460 • Number of events 66 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.	15.0% 69/460 • Number of events 76 • Baseline up to 22 months All participants who received at least one dose of the study drug, regardless of their eligibility for the study.