Trial Outcomes & Findings for Safety and Efficacy of Anamorelin HCl in Patients With Non-Small Cell Lung Cancer-Cachexia (ROMANA 1) (NCT NCT01387269)

Last Updated: 2017-10-27

Results Overview

Change in Lean Body Mass (LBM) from baseline over 12 weeks for the ITT Population. Change from baseline over 12 weeks was defined as the average of the change from baseline at Week 6 and the change from baseline at Week 12.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

484 participants

Primary outcome timeframe

Change in Lean Body Mass from Baseline Over 12 Weeks

Results posted on

2017-10-27

Participant Flow

Approximately 477 patients with advanced NSCLC-C (defined as unresectable Stage III and Stage IV and a weight loss of ≥ 5% body weight within 6 months prior to screening or a screening body mass index \[BMI\] \< 20 kg/m2) were to be randomized 2:1 to anamorelin HCl 100 mg or placebo.

Central randomization stratified patients by geographic region, by chemotherapy and/or radiation therapy status and by weight loss over prior 6 months.

Participant milestones

Participant milestones
Measure	Anamorelin HCl Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Overall Study STARTED	323	161
Overall Study ITT Population	323	161
Overall Study MITT Population	284	141
Overall Study Safety Population	320	161
Overall Study COMPLETED	231	121
Overall Study NOT COMPLETED	92	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Anamorelin HCl Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Overall Study Death	38	20
Overall Study Other	8	7
Overall Study Unrelated AE	12	3
Overall Study Withdrawal by patient	32	10
Overall Study Study drug-related AE	1	0
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Safety and Efficacy of Anamorelin HCl in Patients With Non-Small Cell Lung Cancer-Cachexia (ROMANA 1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anamorelin HCl n=323 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=161 Participants Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Total n=484 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	215 Participants n=5 Participants	105 Participants n=7 Participants	320 Participants n=5 Participants
Age, Categorical >=65 years	108 Participants n=5 Participants	56 Participants n=7 Participants	164 Participants n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	40 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Male	247 Participants n=5 Participants	121 Participants n=7 Participants	368 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 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
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	319 Participants n=5 Participants	159 Participants n=7 Participants	478 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Russian Federation	8 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Serbia	10 participants n=5 Participants	3 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Ukraine	133 participants n=5 Participants	66 participants n=7 Participants	199 participants n=5 Participants
Region of Enrollment Belarus	15 participants n=5 Participants	9 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	11 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Canada	9 participants n=5 Participants	6 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Netherlands	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Poland	48 participants n=5 Participants	26 participants n=7 Participants	74 participants n=5 Participants
Region of Enrollment Slovenia	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Spain	13 participants n=5 Participants	3 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Belgium	11 participants n=5 Participants	4 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Czech Republic	16 participants n=5 Participants	11 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment France	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Germany	10 participants n=5 Participants	3 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Italy	9 participants n=5 Participants	5 participants n=7 Participants	14 participants n=5 Participants
Geographic region North America	35 Participants n=5 Participants	17 Participants n=7 Participants	52 Participants n=5 Participants
Geographic region West Europe	122 Participants n=5 Participants	62 Participants n=7 Participants	184 Participants n=5 Participants
Geographic region East Europe + Russia	166 Participants n=5 Participants	82 Participants n=7 Participants	248 Participants n=5 Participants
Geographic region Australia	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change in Lean Body Mass from Baseline Over 12 Weeks

Population: Intent-to-Treat Population. Some patients in the ITT population were excluded from the primary LBM/HGS analysis (i.e., multiple imputations/ranking method) if they survived to Week 12 but missed their baseline covariates including LBM, HGS, or ECOG OR had Week 6 and Week 12 outcomes that were outside the visit windows.

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=316 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=158 Participants Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Change in Lean Body Mass	0.99 kg Interval 0.61 to 1.36	-0.47 kg Interval -1.0 to 0.21

PRIMARY outcome

Timeframe: Change in Handgrip Strength of the Non-Dominant Hand from Baseline Over 12 Weeks

Change in Handgrip Strength (HGS) of the non-dominant hand from baseline over 12 weeks for the ITT Population. Change from baseline over 12 weeks was defined as the average of the change from baseline at Week 6 and the change from baseline at Week 12.

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=316 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=158 Participants Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Change in Handgrip Strength	-1.10 kg Interval -1.69 to -0.4	-1.58 kg Interval -2.99 to -1.14

SECONDARY outcome

Timeframe: Change in FAACT A/CS Domain Score from Baseline Over 12 Weeks

Population: Modified Intent-to-Treat Population

The Functional Assessment of Anorexia/Cachexia Treatment (FAACT) Additional Concerns Subscale (A/CS domain) is a 12-item scale that is part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. Each item is answered on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). The 12-items are summed together to obtain the domain score. Note that negatively phrased questions are reverse scored so that higher scores always represent improvement/less symptom burden. The total possible score for the A/CS domain ranges from 0 (worst) to 48 (best).

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=284 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=141 Participants Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Change in A/CS Domain Score	4.12 scores on a scale Standard Error 0.752	1.92 scores on a scale Standard Error 0.805

SECONDARY outcome

Timeframe: Change in FACIT-F Fatigue Domain Score from Baseline Over 12 Weeks

Population: Modified Intent-to-Treat Population

The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) fatigue domain is a 13-item scale that is part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. Each item is answered on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). The 13-items are summed together to obtain the domain score. Note that negatively phrased questions are reverse scored so that higher scores always represent improvement/less symptom burden. The total possible score for the FACIT-F fatigue domain ranges from 0 (worst) to 52 (best).

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=284 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=141 Participants Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Change in FACIT-F Fatigue Domain Score	0.26 scores on a scale Standard Error 0.886	-1.19 scores on a scale Standard Error 0.933

SECONDARY outcome

Timeframe: Change in Body Weight from Baseline Over 12 Weeks

Population: Modified Intent-to-Treat Population

Change in body weight (BW) from baseline overall (i.e., over 12 weeks) for the MITT Population.

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=284 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=141 Participants Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Change in Body Weight	2.20 kg Standard Error 0.326	0.14 kg Standard Error 0.363

Adverse Events

Anamorelin HCl

Serious events: 82 serious events

Other events: 182 other events

Deaths: 0 deaths

Placebo

Serious events: 48 serious events

Other events: 84 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Richard K. Bourne, Ph.D.

Helsinn Therapeutics (US), Inc.

Phone: 732-603-2852

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor intends to publish the complete study results in a timely manner that is appropriate to the project. Separate publication of a portion of the study results by any PI is discouraged.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Anamorelin HCl n=320 participants at risk Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=161 participants at risk Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Vascular disorders Deep vein thrombosis	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Vascular disorders Iliac artery occlusion	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Vascular disorders Inferior vena caval occlusion	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	7.5% 24/320 • Number of events 24 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	7.5% 12/161 • Number of events 12 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders Death	0.62% 2/320 • Number of events 2 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders General physical health deterioration	0.94% 3/320 • Number of events 3 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders Pain	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders Pyrexia	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders Asthenia	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders Fatigue	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Psychiatric disorders Mental status changes	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Psychiatric disorders Agitation	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Cardiac disorders Pericardial effusion	0.62% 2/320 • Number of events 2 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Cardiac disorders Arrhythmia	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Cardiac disorders Cardiac arrest	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	1.2% 2/161 • Number of events 2 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Cardiac disorders Myocardial infarction	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Cardiac disorders Atrial flutter	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Cardiac disorders Cardiopulmonary failure	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Cardiac disorders Atrial fibrillation	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Cardiac disorders Ischaemic cardiomyopathy	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Anaemia	1.6% 5/320 • Number of events 6 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	1.9% 3/161 • Number of events 3 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	1.9% 3/161 • Number of events 3 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Neutropenia	0.62% 2/320 • Number of events 2 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Pancytopenia	0.94% 3/320 • Number of events 3 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Thrombocytopenia	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	1.9% 3/161 • Number of events 3 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Leukocytosis	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Idiopathic thrombocytopenic purpura	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Leukopenia	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.2% 4/320 • Number of events 5 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	1.9% 3/161 • Number of events 4 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.94% 3/320 • Number of events 3 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.94% 3/320 • Number of events 3 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	1.2% 2/161 • Number of events 3 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	1.2% 2/161 • Number of events 2 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/320 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.62% 2/320 • Number of events 2 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Nervous system disorders Presyncope	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Nervous system disorders Ischaemic stroke	0.31% 1/320 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.00% 0/161 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.

Other adverse events
Measure	Anamorelin HCl n=320 participants at risk Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=161 participants at risk Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Investigations Alanine aminotransferase increased	15.6% 50/320 • Number of events 78 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	8.7% 14/161 • Number of events 20 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Investigations Aspartate aminotransferase increased	11.6% 37/320 • Number of events 52 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	9.3% 15/161 • Number of events 21 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Investigations Blood alkaline phosphatase increased	10.6% 34/320 • Number of events 40 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	6.2% 10/161 • Number of events 14 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Investigations Platelet count decreased	4.4% 14/320 • Number of events 30 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	6.2% 10/161 • Number of events 16 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Cough	4.4% 14/320 • Number of events 14 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	5.0% 8/161 • Number of events 9 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 19/320 • Number of events 24 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	6.8% 11/161 • Number of events 13 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Anaemia	37.2% 119/320 • Number of events 179 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	41.0% 66/161 • Number of events 114 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Leukopenia	5.0% 16/320 • Number of events 17 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	6.2% 10/161 • Number of events 10 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Neutropenia	8.8% 28/320 • Number of events 34 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	13.7% 22/161 • Number of events 34 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Blood and lymphatic system disorders Thrombocytopenia	9.1% 29/320 • Number of events 42 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	14.3% 23/161 • Number of events 34 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders Asthenia	5.9% 19/320 • Number of events 23 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	5.6% 9/161 • Number of events 10 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders Fatigue	7.8% 25/320 • Number of events 28 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	8.1% 13/161 • Number of events 15 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
General disorders Pyrexia	4.7% 15/320 • Number of events 16 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	0.62% 1/161 • Number of events 1 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Gastrointestinal disorders Diarrhoea	5.3% 17/320 • Number of events 21 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	5.6% 9/161 • Number of events 9 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Gastrointestinal disorders Nausea	9.1% 29/320 • Number of events 44 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	9.3% 15/161 • Number of events 21 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Gastrointestinal disorders Vomiting	7.8% 25/320 • Number of events 27 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	5.0% 8/161 • Number of events 8 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Metabolism and nutrition disorders Decreased appetite	4.1% 13/320 • Number of events 15 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	5.0% 8/161 • Number of events 8 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
Metabolism and nutrition disorders Hyperglycaemia	10.9% 35/320 • Number of events 41 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.	6.2% 10/161 • Number of events 11 • Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit. Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.