Trial Outcomes & Findings for A Study of Abiraterone Acetate Plus Prednisone With or Without Exemestane in Postmenopausal Women With Estrogen Receptor-Positive (ER+) Metastatic Breast Cancer Progressing After Letrozole or Anastrozole Therapy (NCT NCT01381874)

Last Updated: 2019-04-11

Results Overview

Progression-free survival was defined as the time from randomization to first occurrence of disease progression (either radiographic or clinical), or death from any cause. PFS was determined using radiographic progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) on measurable lesions captured by computed tomography (CT) or magnetic resonance imaging (MRI). Clinical disease progression was considered only when disease progression could not be confirmed by CT or MRI, such as when the disease site is skin, bone marrow, or central nervous system.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

297 participants

Primary outcome timeframe

Approximately 2 years

Results posted on

2019-04-11

Participant Flow

Participant milestones

Participant milestones
Measure	Exemestane Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Overall Study STARTED	102	89	106
Overall Study Treated	102	87	104
Overall Study COMPLETED	25	26	30
Overall Study NOT COMPLETED	77	63	76

Reasons for withdrawal

Reasons for withdrawal
Measure	Exemestane Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Overall Study Lost to Follow-up	1	1	0
Overall Study Withdrawal by Subject	9	10	9
Overall Study Other	67	52	67

Baseline Characteristics

A Study of Abiraterone Acetate Plus Prednisone With or Without Exemestane in Postmenopausal Women With Estrogen Receptor-Positive (ER+) Metastatic Breast Cancer Progressing After Letrozole or Anastrozole Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Exemestane n=102 Participants Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=89 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=106 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Total n=297 Participants Total of all reporting groups
Age, Continuous	61.9 years STANDARD_DEVIATION 8.55 • n=5 Participants	63.1 years STANDARD_DEVIATION 9.17 • n=7 Participants	63.8 years STANDARD_DEVIATION 10.91 • n=5 Participants	62.9 years STANDARD_DEVIATION 9.63 • n=4 Participants
Sex: Female, Male Female	102 Participants n=5 Participants	89 Participants n=7 Participants	106 Participants n=5 Participants	297 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	84 Participants n=5 Participants	72 Participants n=7 Participants	95 Participants n=5 Participants	251 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants	15 Participants n=7 Participants	10 Participants n=5 Participants	43 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	7 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	92 Participants n=5 Participants	76 Participants n=7 Participants	96 Participants n=5 Participants	264 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	11 Participants n=7 Participants	4 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment USA	9 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	28 Participants n=4 Participants
Region of Enrollment Belgium	18 Participants n=5 Participants	21 Participants n=7 Participants	21 Participants n=5 Participants	60 Participants n=4 Participants
Region of Enrollment France	17 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	41 Participants n=4 Participants
Region of Enrollment Spain	11 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants	30 Participants n=4 Participants
Region of Enrollment United Kingdom	7 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	30 Participants n=4 Participants
Region of Enrollment Italy	0 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment Korea, Republic Of	1 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment Netherlands	8 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants
Region of Enrollment Russia	20 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants	51 Participants n=4 Participants
Region of Enrollment Ukraine	11 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	25 Participants n=4 Participants

PRIMARY outcome

Timeframe: Approximately 2 years

Population: Intent-to-Treat (ITT) analysis set included all participants randomized into the study.

Outcome measures

Outcome measures
Measure	Exemestane n=102 Participants Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=89 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=106 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Progression-Free Survival (PFS)	3.68 Months Interval 1.94 to 5.26	3.65 Months Interval 2.73 to 5.59	4.47 Months Interval 3.68 to 5.59

PRIMARY outcome

Timeframe: Approximately 3 years

Population: ITT analysis set included all participants randomized into the study.

OS was calculated as the time from randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Exemestane n=102 Participants Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=89 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=106 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Overall Survival (OS)	NA Months Here 'NA' represents that median, lower limit and upper limit of confidence interval (CI) was not estimable due to lesser number of events (high rate of censoring).	26.41 Months Interval 23.49 to Here 'NA' represents that upper limit of CI was not estimable due to lesser number of events (high rate of censoring).	NA Months Interval 23.79 to Here 'NA' represents that median and upper limit of CI was not estimable due to lesser number of events (high rate of censoring).

SECONDARY outcome

Timeframe: Approximately 2 years

Population: ITT analysis set with measurable disease at baseline.

Overall response rate was defined as the percentage of participants with measurable disease achieving a best overall response of either complete response (CR) or partial response (PR) based on RECIST. CR: disappearance of all target lesions and non-target lesions. PR: at least a 30 percent (%) decrease in the sum of longest diameter (LD) of target lesions or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

Outcome measures

Outcome measures
Measure	Exemestane n=63 Participants Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=52 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=66 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Overall Response Rate (ORR)	6.3 Percentage of participants	5.8 Percentage of participants	12.1 Percentage of participants

SECONDARY outcome

Timeframe: Approximately 2 years

Population: ITT analysis set with measurable disease at baseline.

Clinical benefit rate was defined as the percentage of participants with measurable disease achieving a best overall response of a CR, PR, or stable disease (SD) for at least 6 months based on RECIST. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

Outcome measures

Outcome measures
Measure	Exemestane n=63 Participants Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=52 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=66 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Clinical Benefit Rate	12.7 Percentage of participants	9.6 Percentage of participants	22.7 Percentage of participants

SECONDARY outcome

Timeframe: Approximately 2 years

Population: ITT analysis set with measurable disease at baseline with complete or partial response.

Duration of objective response was measured from the first time that the CR or PR was achieved to the first observation of disease progression (either radiographic or clinical) based on the RECIST criteria.

Outcome measures

Outcome measures
Measure	Exemestane n=4 Participants Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=3 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=8 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Duration of Response	6.47 months Here 'NA' represents that lower limit and upper limit of CI was not estimable due to lesser number of events (high rate of censoring).	4.86 months Interval 4.63 to Here 'NA' represents that upper limit of CI was not estimable due to lesser number of events (high rate of censoring).	6.93 months Interval 4.57 to Here 'NA' represents that upper limit of CI was not estimable due to lesser number of events (high rate of censoring).

SECONDARY outcome

Timeframe: Baseline and End of treatment (approximately 2 years)

Population: ITT analysis set with valid baseline value and at least 1 post baseline value. Here "n" (number analyzed)" signifies participants evaluable for specified categories.

Change from baseline in serum endocrine biomarkers (estradiol and estrone) was summarized by treatment at end of treatment.

Outcome measures

Outcome measures
Measure	Exemestane n=50 Participants Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=49 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=56 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Change From Baseline in Serum Endocrine Biomarkers (Estradiol and Estrone) at End of Treatment Estradiol	1.53 Picomoles Per Liter (Pmol/L) Standard Deviation 27.643	-3.35 Picomoles Per Liter (Pmol/L) Standard Deviation 13.634	-1.04 Picomoles Per Liter (Pmol/L) Standard Deviation 20.146
Change From Baseline in Serum Endocrine Biomarkers (Estradiol and Estrone) at End of Treatment Estrone	-34.20 Picomoles Per Liter (Pmol/L) Standard Deviation 83.770	-28.09 Picomoles Per Liter (Pmol/L) Standard Deviation 47.779	-30.60 Picomoles Per Liter (Pmol/L) Standard Deviation 42.385

SECONDARY outcome

Timeframe: Baseline and End of treatment (approximately 2 years)

Population: ITT analysis set with valid baseline value and at least 1 post baseline value. Here "n" (number analyzed)" signifies participants evaluable for specified categories.

Change from baseline in serum endocrine biomarkers (Progesterone and Testosterone) was summarized by treatment at end of treatment.

Outcome measures

Outcome measures
Measure	Exemestane n=53 Participants Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=50 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=56 Participants Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Change From Baseline in Serum Endocrine Biomarkers (Progesterone and Testosterone) at End of Treatment Progesterone	-4.80 Nanomoles Per Liter (nmol/L) Standard Deviation 18.268	8.98 Nanomoles Per Liter (nmol/L) Standard Deviation 15.113	12.34 Nanomoles Per Liter (nmol/L) Standard Deviation 16.967
Change From Baseline in Serum Endocrine Biomarkers (Progesterone and Testosterone) at End of Treatment Testosterone	-0.09 Nanomoles Per Liter (nmol/L) Standard Deviation 0.416	-0.51 Nanomoles Per Liter (nmol/L) Standard Deviation 0.459	-0.48 Nanomoles Per Liter (nmol/L) Standard Deviation 0.323

Adverse Events

Exemestane

Serious events: 12 serious events

Other events: 79 other events

Deaths: 1 deaths

Abiraterone Acetate + Prednisone

Serious events: 18 serious events

Other events: 76 other events

Deaths: 0 deaths

Abiraterone Acetate + Exemestane + Prednisone

Serious events: 28 serious events

Other events: 84 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Director Clinical Development

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Exemestane n=102 participants at risk Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Prednisone n=87 participants at risk Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Abiraterone Acetate + Exemestane + Prednisone n=104 participants at risk Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Blood and lymphatic system disorders Anaemia	6.9% 7/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	6.9% 6/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.7% 9/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal Pain	6.9% 7/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	4.6% 4/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	13.5% 14/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	8.8% 9/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	16.1% 14/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	14.4% 15/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	8.8% 9/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.7% 5/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	12.5% 13/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	2.9% 3/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.7% 5/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.8% 6/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	17.6% 18/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	24.1% 21/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	21.2% 22/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	6.9% 7/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	13.8% 12/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	18.3% 19/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
General disorders Asthenia	11.8% 12/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.7% 5/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.7% 9/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
General disorders Fatigue	26.5% 27/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	27.6% 24/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	20.2% 21/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
General disorders Influenza Like Illness	6.9% 7/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	0.00% 0/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	1.9% 2/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
General disorders Oedema Peripheral	6.9% 7/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	6.9% 6/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	9.6% 10/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Infections and infestations Bronchitis	3.9% 4/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.0% 7/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	7.7% 8/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	10.8% 11/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.7% 5/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.7% 9/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Infections and infestations Urinary Tract Infection	0.00% 0/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	6.9% 6/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.8% 6/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Investigations Alanine Aminotransferase Increased	6.9% 7/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.7% 5/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	10.6% 11/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Investigations Aspartate Aminotransferase Increased	7.8% 8/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.7% 5/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	13.5% 14/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Investigations Weight Decreased	3.9% 4/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	1.1% 1/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	7.7% 8/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased Appetite	10.8% 11/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	14.9% 13/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	16.3% 17/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercholesterolaemia	0.98% 1/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	0.00% 0/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.8% 6/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	5.9% 6/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	3.4% 3/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	6.7% 7/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	3.9% 4/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	21.8% 19/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	13.5% 14/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 17/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	9.2% 8/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	10.6% 11/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	11.8% 12/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	17.2% 15/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	16.3% 17/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone Pain	17.6% 18/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	14.9% 13/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	12.5% 13/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle Spasms	2.0% 2/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.7% 5/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	6.7% 7/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	5.9% 6/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.0% 7/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.7% 9/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	10.8% 11/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	4.6% 4/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	4.8% 5/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in Extremity	6.9% 7/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.0% 7/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	9.6% 10/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Nervous system disorders Dizziness	6.9% 7/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	4.6% 4/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	7.7% 8/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	2.0% 2/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.7% 5/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	0.96% 1/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	9.8% 10/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	6.9% 6/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	14.4% 15/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	8.8% 9/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	4.6% 4/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	4.8% 5/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	3.9% 4/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	10.3% 9/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	11.5% 12/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.8% 8/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	6.9% 6/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	13.5% 14/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	6.9% 6/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	2.9% 3/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	2.0% 2/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	1.1% 1/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	5.8% 6/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Vascular disorders Hot Flush	13.7% 14/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	16.1% 14/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.7% 9/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.
Vascular disorders Hypertension	9.8% 10/102 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	8.0% 7/87 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.	14.4% 15/104 • Approximately 3 years Safety population was defined as all randomized participants who received at least one dose of study drug.