Trial Outcomes & Findings for A Study of Flexible Dose Brexpiprazole as Monotherapy or Combination Therapy in the Treatment of Adults With Post-traumatic Stress Disorder (PTSD) (NCT NCT03033069)

Last Updated: 2021-12-08

Results Overview

CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from categories: Category B:Intrusion symptoms (5 items); Category C:Avoidance symptoms (2 items); Category D:Cognition and mood symptoms (7 items); Category E:Arousal and reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B,C,D,E. Each symptom was scored 0 (Absent) to 4 (Extreme/incapacitating), to yield a score with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

336 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2021-12-08

Participant Flow

Participants took part in the study at 48 investigative sites in the United States from 26 January 2017 to 12 November 2018.

Of the 336 participants enrolled in the study, 321 participants diagnosed with post-traumatic stress disorder (PTSD) were randomized in 1:1:1:1 ratio to receive brexpiprazole monotherapy, brexpiprazole plus sertraline combination therapy, sertraline monotherapy or placebo up to Week 12.

Participant milestones

Participant milestones
Measure	Brexpiprazole + Sertraline Participants were administered oral brexpiprazole initial dose of 0.5 milligram (mg)/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.	Brexpiprazole Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.	Sertraline Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.	Placebo Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
Overall Study STARTED	82	75	81	83
Overall Study Safety Sample	80	75	79	82
Overall Study Intent to Treat (ITT) Sample	79	72	77	80
Overall Study COMPLETED	58	50	59	64
Overall Study NOT COMPLETED	24	25	22	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Brexpiprazole + Sertraline Participants were administered oral brexpiprazole initial dose of 0.5 milligram (mg)/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.	Brexpiprazole Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.	Sertraline Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.	Placebo Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
Overall Study Adverse Event	6	7	4	6
Overall Study Lack of Efficacy	0	0	1	0
Overall Study Lost to Follow-up	6	5	5	6
Overall Study Non-Compliance With Study Drug	1	1	1	0
Overall Study Protocol Deviation	0	1	0	0
Overall Study Withdrawal by Subject	10	10	11	6
Overall Study Withdrawal By Caregiver	1	0	0	0
Overall Study Reason not Specified	0	1	0	1

Baseline Characteristics

A Study of Flexible Dose Brexpiprazole as Monotherapy or Combination Therapy in the Treatment of Adults With Post-traumatic Stress Disorder (PTSD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brexpiprazole + Sertraline n=82 Participants Participants were administered oral brexpiprazole initial dose of 0.5 mg/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.	Brexpiprazole n=75 Participants Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.	Sertraline n=81 Participants Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.	Placebo n=83 Participants Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week12.	Total n=321 Participants Total of all reporting groups
Age, Continuous	38.4 years STANDARD_DEVIATION 11.9 • n=5 Participants	39.3 years STANDARD_DEVIATION 10.6 • n=7 Participants	38.6 years STANDARD_DEVIATION 10.9 • n=5 Participants	40.3 years STANDARD_DEVIATION 11.0 • n=4 Participants	39.2 years STANDARD_DEVIATION 11.1 • n=21 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	49 Participants n=7 Participants	51 Participants n=5 Participants	48 Participants n=4 Participants	199 Participants n=21 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	26 Participants n=7 Participants	30 Participants n=5 Participants	35 Participants n=4 Participants	122 Participants n=21 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Race · Black or African American	21 Participants n=5 Participants	23 Participants n=7 Participants	22 Participants n=5 Participants	26 Participants n=4 Participants	92 Participants n=21 Participants
Race/Ethnicity, Customized Race · White	55 Participants n=5 Participants	43 Participants n=7 Participants	53 Participants n=5 Participants	46 Participants n=4 Participants	197 Participants n=21 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants	22 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	13 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	14 Participants n=4 Participants	49 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	68 Participants n=5 Participants	64 Participants n=7 Participants	70 Participants n=5 Participants	69 Participants n=4 Participants	271 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	82 Participants n=5 Participants	75 Participants n=7 Participants	81 Participants n=5 Participants	83 Participants n=4 Participants	321 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: ITT Sample included all participants who were randomized in the trial and took at least one dose of double-blind investigational medicinal product (IMP) and have a Baseline and at least one post Baseline evaluation for the CAPS-5 total score. Overall number of participants analyzed are the number of participants with data available for analyses.

Outcome measures

Outcome measures
Measure	Brexpiprazole + Sertraline n=59 Participants Participants were administered oral brexpiprazole initial dose of 0.5 mg/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.	Brexpiprazole n=48 Participants Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.	Sertraline n=58 Participants Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.	Placebo n=62 Participants Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score	-16.4 score on a scale Standard Error 1.43	-12.2 score on a scale Standard Error 1.57	-11.4 score on a scale Standard Error 1.46	-10.5 score on a scale Standard Error 1.40

Adverse Events

Brexpiprazole + Sertraline

Serious events: 2 serious events

Other events: 47 other events

Deaths: 0 deaths

Brexpiprazole

Serious events: 1 serious events

Other events: 42 other events

Deaths: 0 deaths

Sertraline

Serious events: 0 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 43 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Brexpiprazole + Sertraline n=80 participants at risk Participants were administered oral brexpiprazole initial dose of 0.5 mg/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.	Brexpiprazole n=75 participants at risk Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.	Sertraline n=79 participants at risk Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.	Placebo n=82 participants at risk Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
General disorders Chest pain	0.00% 0/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.2% 1/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Hepatobiliary disorders Bile duct stone	0.00% 0/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.2% 1/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Injury, poisoning and procedural complications Animal bite	0.00% 0/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Musculoskeletal and connective tissue disorders Back pain	1.2% 1/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.2% 1/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.2% 1/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Psychiatric disorders Suicide attempt	1.2% 1/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.

Other adverse events

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
Publication restrictions are in place

Restriction type: OTHER

Measure	Brexpiprazole + Sertraline n=80 participants at risk Participants were administered oral brexpiprazole initial dose of 0.5 mg/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.	Brexpiprazole n=75 participants at risk Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.	Sertraline n=79 participants at risk Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.	Placebo n=82 participants at risk Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.
Gastrointestinal disorders Constipation	5.0% 4/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	2.7% 2/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	5.1% 4/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	4.9% 4/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Gastrointestinal disorders Diarrhoea	6.2% 5/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	4.0% 3/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.9% 7/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	6.1% 5/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Gastrointestinal disorders Dry mouth	6.2% 5/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.0% 6/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	12.7% 10/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.5% 7/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Gastrointestinal disorders Nausea	5.0% 4/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	20.3% 16/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	4.9% 4/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Gastrointestinal disorders Vomiting	1.2% 1/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	5.1% 4/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
General disorders Fatigue	2.5% 2/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.0% 6/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	5.1% 4/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Infections and infestations Upper respiratory tract infection	3.8% 3/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	9.3% 7/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.9% 7/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.5% 7/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Investigations Weight increase	12.5% 10/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.0% 6/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.5% 7/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Metabolism and nutrition disorders Decreased appetite	7.5% 6/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	6.7% 5/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.2% 1/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Nervous system disorders Akathisia	6.2% 5/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	13.3% 10/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	3.8% 3/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	2.4% 2/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Nervous system disorders Dizziness	2.5% 2/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	2.7% 2/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	6.3% 5/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	6.1% 5/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Nervous system disorders Headache	7.5% 6/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	5.3% 4/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.9% 7/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.5% 7/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Nervous system disorders Sedation	3.8% 3/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	6.7% 5/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Nervous system disorders Somnolence	10.0% 8/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	6.7% 5/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	3.8% 3/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	8.5% 7/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Psychiatric disorders Anorgasmia	5.0% 4/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Psychiatric disorders Anxiety	3.8% 3/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	5.3% 4/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	4.9% 4/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Psychiatric disorders Insomnia	2.5% 2/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	6.7% 5/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	5.1% 4/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	3.7% 3/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Psychiatric disorders Irritability	3.8% 3/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	5.1% 4/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	3.7% 3/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Reproductive system and breast disorders Delayed ejaculation	5.0% 4/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.
Skin and subcutaneous tissue disorders Dermatitis Contact	5.0% 4/80 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	0.00% 0/75 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.3% 1/79 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.	1.2% 1/82 • From the first dose of the study drug up to 14 days after the last dose (Up to Week 14) Safety Sample included all participants who were randomized into this trial and were administered at least one dose of double-blind IMP.