Trial Outcomes & Findings for A Study of Rapastinel as Adjunctive Therapy in the Prevention of Relapse in Patients With Major Depressive Disorder (NCT NCT02951988)

NCT ID: NCT02951988

Last Updated: 2020-03-09

Results Overview

The time in days to first relapse is defined as the number of days from the date of randomization to the first relapse.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1304 participants
• Primary outcome timeframe: 52 Weeks
• Results posted on: 2020-03-09

Participant Flow

Patients from RAP-MD-04, completed 1 of the rapastinel lead-in studies - RAP-MD-01, RAP-MD-02, or RAP-MD-03.

A total of 1304 patients enrolled in the Open Label Treatment Period (OLTP). Of these, 1056 completed the OLTP and 604 entered the Double Blind Treatment Period (DBTP) and were randomized.

Participant milestones

Measure	OLTP Rapastinel 450 mg Weekly + ADT Rapastinel 450 milligrams (mg) intravenous (IV) once a week during OLTP.	DBTP Placebo Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP.	DBTP Rapastinel 450 mg Every 2 Weeks Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks.	DBTP Rapastinel 450 mg Weekly Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP.
Open-Label Treatment Period STARTED	1304	0	0	0
Open-Label Treatment Period COMPLETED	1056	0	0	0
Open-Label Treatment Period NOT COMPLETED	248	0	0	0
Double-Blind Treatment Period STARTED	0	202	202	200
Double-Blind Treatment Period COMPLETED	0	101	101	85
Double-Blind Treatment Period NOT COMPLETED	0	101	101	115

Reasons for withdrawal

Measure	OLTP Rapastinel 450 mg Weekly + ADT Rapastinel 450 milligrams (mg) intravenous (IV) once a week during OLTP.	DBTP Placebo Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP.	DBTP Rapastinel 450 mg Every 2 Weeks Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks.	DBTP Rapastinel 450 mg Weekly Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP.
Open-Label Treatment Period Miscellaneous Reasons	8	0	0	0
Open-Label Treatment Period Study terminated by sponsor	9	0	0	0
Open-Label Treatment Period Non-compliance with background ADT	2	0	0	0
Open-Label Treatment Period Non-compliance with study drug	5	0	0	0
Open-Label Treatment Period Protocol Violation	22	0	0	0
Open-Label Treatment Period Pregnancy	2	0	0	0
Open-Label Treatment Period Lost to Follow-up	28	0	0	0
Open-Label Treatment Period Withdrawal by Subject	78	0	0	0
Open-Label Treatment Period Lack of Efficacy	49	0	0	0
Open-Label Treatment Period Adverse Event	45	0	0	0
Double-Blind Treatment Period Site terminated by sponsor	0	0	1	1
Double-Blind Treatment Period Study terminated by sponsor	0	58	54	69
Double-Blind Treatment Period Non-compliance with study drug	0	1	3	0
Double-Blind Treatment Period Protocol Violation	0	4	4	8
Double-Blind Treatment Period Pregnancy	0	1	1	0
Double-Blind Treatment Period Lost to Follow-up	0	4	12	3
Double-Blind Treatment Period Withdrawal by Subject	0	23	22	28
Double-Blind Treatment Period Adverse Event	0	8	3	6
Double-Blind Treatment Period Miscellaneous Reasons	0	2	1	0

Baseline Characteristics

A Study of Rapastinel as Adjunctive Therapy in the Prevention of Relapse in Patients With Major Depressive Disorder

Baseline characteristics by cohort

Measure	Placebo n=202 Participants Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP.	Rapastinel 450 mg Every 2 Weeks n=202 Participants Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks during DBTP.	Rapastinel 450 mg Weekly n=200 Participants Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP.	Total n=604 Participants Total of all reporting groups
Age, Continuous	45.2 Years STANDARD_DEVIATION 12.45 • n=5 Participants	45.4 Years STANDARD_DEVIATION 12.17 • n=7 Participants	44.7 Years STANDARD_DEVIATION 12.15 • n=5 Participants	45.1 Years STANDARD_DEVIATION 12.24 • n=4 Participants
Sex: Female, Male Female	148 Participants n=5 Participants	142 Participants n=7 Participants	152 Participants n=5 Participants	442 Participants n=4 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	60 Participants n=7 Participants	48 Participants n=5 Participants	162 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	29 Participants n=7 Participants	29 Participants n=5 Participants	83 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	177 Participants n=5 Participants	173 Participants n=7 Participants	171 Participants n=5 Participants	521 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	162 Participants n=5 Participants	170 Participants n=7 Participants	162 Participants n=5 Participants	494 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	35 Participants n=5 Participants	27 Participants n=7 Participants	29 Participants n=5 Participants	91 Participants n=4 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Weight	86.49 kg STANDARD_DEVIATION 19.15 • n=5 Participants	88.29 kg STANDARD_DEVIATION 18.78 • n=7 Participants	85.39 kg STANDARD_DEVIATION 17.46 • n=5 Participants	86.73 kg STANDARD_DEVIATION 18.49 • n=4 Participants
Height	167.27 cm STANDARD_DEVIATION 8.85 • n=5 Participants	168.12 cm STANDARD_DEVIATION 9.78 • n=7 Participants	167.36 cm STANDARD_DEVIATION 9.13 • n=5 Participants	167.58 cm STANDARD_DEVIATION 9.25 • n=4 Participants
BMI	30.94 kg/m^2 STANDARD_DEVIATION 6.74 • n=5 Participants	31.33 kg/m^2 STANDARD_DEVIATION 6.83 • n=7 Participants	30.45 kg/m^2 STANDARD_DEVIATION 5.69 • n=5 Participants	30.91 kg/m^2 STANDARD_DEVIATION 6.44 • n=4 Participants

PRIMARY outcome

Timeframe: 52 Weeks

Population: The Double-blind modified Intent-to-Treat Population consists of all patients in the Open-label Safety Population who were randomized to a treatment group during the DBTP of the study and received at least 1 dose of IP during the DBTP.

The time in days to first relapse is defined as the number of days from the date of randomization to the first relapse.

Outcome measures

Measure	Placebo n=202 Participants Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP.	Rapastinel 450 mg Every 2 Weeks n=202 Participants Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks during DBTP.	Rapastinel 450 mg Weekly n=200 Participants Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP.
Time to First Relapse During the First 52 Weeks of the Double-Blind Treatment Period	232 Days Interval 167.0 to Not enough events to allow the estimation of the percentiles and the standard error for the confidence intervals.	225 Days Interval 127.0 to 323.0	336 Days Interval 157.0 to Not enough events to allow the estimation of the percentiles and the standard error for the confidence intervals.

PRIMARY outcome

Timeframe: 104 Weeks

Population: The Double-blind modified Intent-to-Treat Population consists of all patients in the Open-label Safety Population who were randomized to a treatment group during the DBTP of the study and received at least 1 dose of IP during the DBTP. 1 subject in the Biweekly Rapastinel group did not have any responses regarding the C-SSRS during the DBTP.

On the C-SSRS, the 5 types of suicidal ideation are:

Type 1: "Wish to be dead" Type 2: Non-specific active suicidal thoughts Type 3: "Active suicidal ideation with any methods (not plan) without intent to act" Type 4: "Active suicidal ideation with some intent to act, without specific plan" Type 5: "Active suicidal ideation with specific plan and intent"

Outcome measures

Measure	Placebo n=202 Participants Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP.	Rapastinel 450 mg Every 2 Weeks n=201 Participants Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks during DBTP.	Rapastinel 450 mg Weekly n=200 Participants Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP.
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Using 5-Point Scales Suicidal Ideation	17 Participants	25 Participants	23 Participants
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) Using 5-Point Scales Suicidal Behavior	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 104 Weeks

Population: The Double-blind modified Intent-to-Treat Population consists of all patients in the Open-label Safety Population who were randomized to a treatment group during the DBTP of the study and received at least 1 dose of IP during the DBTP.

The time in days to first relapse is defined as the number of days from the date of randomization to the first relapse.

Outcome measures

Measure	Placebo n=202 Participants Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP.	Rapastinel 450 mg Every 2 Weeks n=202 Participants Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks during DBTP.	Rapastinel 450 mg Weekly n=200 Participants Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP.
Time to First Relapse During the Entire Double-Blind Treatment Period	232 Days Interval 167.0 to 492.0	225 Days Interval 127.0 to 323.0	336 Days Interval 157.0 to Not enough events to allow the estimation of the percentiles and the standard error for the confidence intervals.

Adverse Events

OLTP Rapastinel 450 mg Weekly + ADT

Serious events: 26 serious events

Other events: 290 other events

Deaths: 0 deaths

DBTP Placebo

Serious events: 6 serious events

Other events: 62 other events

Deaths: 1 deaths

DBTP Rapastinel 450 mg Every 2 Weeks

Serious events: 3 serious events

Other events: 72 other events

Deaths: 0 deaths

DBTP Rapastinel 450 mg Weekly

Serious events: 5 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Measure	OLTP Rapastinel 450 mg Weekly + ADT n=1304 participants at risk Rapastinel 450 milligrams (mg) intravenous (IV) once a week during OLTP.	DBTP Placebo n=202 participants at risk Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP.	DBTP Rapastinel 450 mg Every 2 Weeks n=202 participants at risk Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks.	DBTP Rapastinel 450 mg Weekly n=200 participants at risk Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP.
Respiratory, thoracic and mediastinal disorders Asthma	0.15% 2/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Bronchitis	0.15% 2/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Psychiatric disorders Major depression	0.15% 2/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Pneumonia	0.15% 2/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Psychiatric disorders Suicidal ideation	0.15% 2/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Gastrointestinal disorders Abdominal pain	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Renal and urinary disorders Acute kidney injury	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Musculoskeletal and connective tissue disorders Back pain	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Nervous system disorders Cerebrovascular accident	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Hepatobiliary disorders Cholecystitis	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Metabolism and nutrition disorders Dehydration	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Reproductive system and breast disorders Endometrial hyperplasia	0.11% 1/920 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Metabolism and nutrition disorders Gout	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma cell type unspecified recurrent	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Reproductive system and breast disorders Menorrhagia	0.11% 1/920 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Gastrointestinal disorders Pancreatitis	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Injury, poisoning and procedural complications Procedural vomiting	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Injury, poisoning and procedural complications Road traffic accident	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Psychiatric disorders Substance abuse	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Psychiatric disorders Substance use disorder	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Psychiatric disorders Suicide attempt	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Nervous system disorders Transient ischaemic attack	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Injury, poisoning and procedural complications Traumatic liver injury	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Upper respiratory tract infection	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Urinary tract infection	0.08% 1/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Product Issues Device dislocation	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Injury, poisoning and procedural complications Fall	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Vascular disorders Hypotension	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Renal and urinary disorders Renal tubular necrosis	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Psychiatric disorders Suicidal behaviour	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Psychiatric disorders Suicide threat	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Renal and urinary disorders Ureterolithiasis	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Injury, poisoning and procedural complications Anastomotic ulcer	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage II	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Gastrointestinal disorders Constipation	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	1.9% 1/54 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/60 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/48 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Abscess intestinal	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Nervous system disorders Altered state of consciousness	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Cardiac disorders Cardiac failure congestive	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Vascular disorders Deep vein thrombosis	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Diverticulitis	0.00% 0/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.50% 1/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	0.00% 0/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.

Other adverse events

Measure	OLTP Rapastinel 450 mg Weekly + ADT n=1304 participants at risk Rapastinel 450 milligrams (mg) intravenous (IV) once a week during OLTP.	DBTP Placebo n=202 participants at risk Rapastinel 450 mg IV once a week during OLTP followed by placebo-matching rapastinel 450 mg IV once a week during DBTP.	DBTP Rapastinel 450 mg Every 2 Weeks n=202 participants at risk Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once every 2 weeks.	DBTP Rapastinel 450 mg Weekly n=200 participants at risk Rapastinel 450 mg IV once a week during OLTP followed by rapastinel 450 mg IV once a week during DBTP.
Infections and infestations Nasopharyngitis	6.1% 79/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	7.4% 15/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	7.9% 16/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	7.5% 15/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Upper respiratory tract infection	5.6% 73/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	9.4% 19/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	7.9% 16/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	12.5% 25/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Nervous system disorders Headache	7.4% 96/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.4% 11/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	6.9% 14/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.0% 10/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Nervous system disorders Dysgeusia	6.8% 89/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	2.5% 5/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	6.9% 14/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	1.0% 2/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Gastrointestinal disorders Nausea	3.8% 49/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	2.5% 5/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.4% 11/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	3.0% 6/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Gastrointestinal disorders Diarrhoea	3.1% 41/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	2.5% 5/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.4% 11/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	2.5% 5/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Bronchitis	0.92% 12/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	2.5% 5/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	2.5% 5/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.0% 10/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Infections and infestations Sinusitis	2.9% 38/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.4% 11/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	4.0% 8/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	3.0% 6/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Investigations Weight increased	2.8% 37/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	2.0% 4/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.4% 11/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	1.5% 3/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.
Psychiatric disorders Insomnia	4.0% 52/1304 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.4% 11/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	5.0% 10/202 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.	3.0% 6/200 • The study consisted of an 8 to 16 week OLTP; followed by a randomized DBTP of up to 104 weeks; followed by a 2 week safety period.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: IR-CTRegistration@allergan.com

Results disclosure agreements

• Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER