Trial Outcomes & Findings for A Six Week, Double-Blind Randomized, Efficacy and Safety, Sleep Lab Trial With Esmirtazapine (Org 50081) (P05707) (NCT NCT00506389)
NCT ID: NCT00506389
Last Updated: 2018-10-02
Results Overview
WASO was defined as the total objective time awake after the onset of persistent sleep until the end of the 8-hour sleep cycle period as measured by polysomnography (PSG). WASO was calculated as the mean of Nights 1, 15, and 36.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
419 participants
Primary outcome timeframe
From Day 1 to Day 36
Results posted on
2018-10-02
Participant Flow
Participant milestones
| Measure |
Esmirtazapine 3.0 mg
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 3.0 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Esmirtazapine 4.5 mg
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 4.5 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Placebo
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, placebo tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
|---|---|---|---|
|
In-treatment Period
STARTED
|
143
|
139
|
137
|
|
In-treatment Period
All Participants Treated
|
139
|
138
|
136
|
|
In-treatment Period
COMPLETED
|
117
|
124
|
125
|
|
In-treatment Period
NOT COMPLETED
|
26
|
15
|
12
|
|
Follow-up Period
STARTED
|
139
|
138
|
136
|
|
Follow-up Period
COMPLETED
|
139
|
138
|
136
|
|
Follow-up Period
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Esmirtazapine 3.0 mg
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 3.0 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Esmirtazapine 4.5 mg
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 4.5 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Placebo
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, placebo tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
|---|---|---|---|
|
In-treatment Period
Other
|
3
|
3
|
4
|
|
In-treatment Period
Lost to Follow-up
|
0
|
0
|
1
|
|
In-treatment Period
Lack of compliance
|
1
|
0
|
0
|
|
In-treatment Period
Reasons not related to trial
|
4
|
1
|
0
|
|
In-treatment Period
Withdrawal by Subject
|
3
|
3
|
4
|
|
In-treatment Period
Lack of Efficacy
|
0
|
2
|
0
|
|
In-treatment Period
Adverse Event
|
11
|
5
|
2
|
|
In-treatment Period
Randomized but not treated
|
4
|
1
|
1
|
Baseline Characteristics
A Six Week, Double-Blind Randomized, Efficacy and Safety, Sleep Lab Trial With Esmirtazapine (Org 50081) (P05707)
Baseline characteristics by cohort
| Measure |
Esmirtazapine 3.0 mg
n=143 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 3.0 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Esmirtazapine 4.5 mg
n=139 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 4.5 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Placebo
n=137 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, placebo tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Total
n=419 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
43.5 Years
STANDARD_DEVIATION 11.3 • n=93 Participants
|
44.5 Years
STANDARD_DEVIATION 11.5 • n=4 Participants
|
46.6 Years
STANDARD_DEVIATION 10.5 • n=27 Participants
|
44.9 Years
STANDARD_DEVIATION 11.2 • n=483 Participants
|
|
Sex: Female, Male
Female
|
98 Participants
n=93 Participants
|
89 Participants
n=4 Participants
|
90 Participants
n=27 Participants
|
277 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=93 Participants
|
50 Participants
n=4 Participants
|
47 Participants
n=27 Participants
|
142 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: From Day 1 to Day 36Population: The Intent-to-Treat (ITT) group consisted of all participants who were randomized, received at least one dose of double-blind trial medication, and had at least one post-randomization efficacy assessment. Fifteen participants from 1 site were excluded from all efficacy analyses.
WASO was defined as the total objective time awake after the onset of persistent sleep until the end of the 8-hour sleep cycle period as measured by polysomnography (PSG). WASO was calculated as the mean of Nights 1, 15, and 36.
Outcome measures
| Measure |
Esmirtazapine 3.0 mg
n=133 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 3.0 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Esmirtazapine 4.5 mg
n=133 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 4.5 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Placebo
n=132 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, placebo tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
|---|---|---|---|
|
Average Wake Time After Sleep Onset (WASO) During the In-Treatment Period
|
45.6 Minutes
Standard Deviation 25.7
|
45.5 Minutes
Standard Deviation 26.5
|
76.1 Minutes
Standard Deviation 46.0
|
SECONDARY outcome
Timeframe: From Day 1 to Day 36Population: The ITT group consisted of all participants who were randomized, received at least one dose of double-blind trial medication, and had at least one post-randomization efficacy assessment. Fifteen participants from 1 site were excluded from all efficacy analyses.
LPS was defined as the time in minutes from lights out to the first 20 consecutive epochs scored as sleep as measured by PSG. LPS was calculated as the mean of Nights 1, 15, and 36.
Outcome measures
| Measure |
Esmirtazapine 3.0 mg
n=133 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 3.0 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Esmirtazapine 4.5 mg
n=133 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 4.5 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Placebo
n=132 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, placebo tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
|---|---|---|---|
|
Average Latency to Persistent Sleep (LPS) During the In-Treatment Period
|
28.7 Minutes
Standard Deviation 28.4
|
26.1 Minutes
Standard Deviation 23.0
|
40.5 Minutes
Standard Deviation 27.3
|
SECONDARY outcome
Timeframe: From Day 1 to Day 36Population: The ITT group consisted of all participants who were randomized, received at least one dose of double-blind trial medication, and had at least one post-randomization efficacy assessment. Fifteen participants from 1 site were excluded from all efficacy analyses.
TST was defined as the total amount of time in minutes that was actually spent sleeping the previous night as recorded daily in the participant's sleep diary. TST values over the 6 week In-Treatment Period were averaged for each participant, and average TST was then reported by treatment arm. For participants with missing data, the average of the nights for which TST data were available was used in the analysis.
Outcome measures
| Measure |
Esmirtazapine 3.0 mg
n=133 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 3.0 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Esmirtazapine 4.5 mg
n=133 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 4.5 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
Placebo
n=132 Participants
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, placebo tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. After this, participants were followed for safety up to Day 50 during the Follow-Up Period.
|
|---|---|---|---|
|
Average Subjective Total Sleep Time (TST) During the In-Treatment Period
|
384.6 Minutes
Standard Deviation 63.6
|
384.6 Minutes
Standard Deviation 66.2
|
351.6 Minutes
Standard Deviation 57.2
|
Adverse Events
Esmirtazapine 3.0 mg In-treatment
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
Esmirtazapine 4.5 mg In-treatment
Serious events: 1 serious events
Other events: 24 other events
Deaths: 0 deaths
Placebo In-treatment
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Esmirtazapine 3.0 mg Follow-up
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Esmirtazapine 4.5 mg Follow-up
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo Follow-up
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Esmirtazapine 3.0 mg In-treatment
n=139 participants at risk
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 3.0 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. Tablets were taken by mouth once daily in the evening.
|
Esmirtazapine 4.5 mg In-treatment
n=138 participants at risk
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 4.5 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. Tablets were taken by mouth once daily in the evening.
|
Placebo In-treatment
n=136 participants at risk
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, placebo tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. Tablets were taken by mouth once daily in the evening.
|
Esmirtazapine 3.0 mg Follow-up
n=139 participants at risk
After participants received placebo tablets during the Placebo Washout Period and 3.0 mg esmirtazapine during the In-treatment Period, participants were followed for safety up to Day 50 during the Follow-up Period.
|
Esmirtazapine 4.5 mg Follow-up
n=138 participants at risk
After participants received placebo tablets during the Placebo Washout Period and 4.5 mg esmirtazapine during the In-treatment Period, participants were followed for safety up to Day 50 during the Follow-up Period.
|
Placebo Follow-up
n=136 participants at risk
After participants received placebo tablets during the Placebo Washout Period and placebo during the In-treatment Period, participants were followed for safety up to Day 50 during the Follow-up Period.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/139 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.72%
1/138 • Number of events 1 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/136 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/139 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/138 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/136 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
|
Infections and infestations
Pneumonia streptococcal
|
0.00%
0/139 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.72%
1/138 • Number of events 1 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/136 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/139 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/138 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/136 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
|
Infections and infestations
Sepsis
|
0.00%
0/139 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.72%
1/138 • Number of events 1 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/136 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/139 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/138 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/136 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
Other adverse events
| Measure |
Esmirtazapine 3.0 mg In-treatment
n=139 participants at risk
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 3.0 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. Tablets were taken by mouth once daily in the evening.
|
Esmirtazapine 4.5 mg In-treatment
n=138 participants at risk
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, esmirtazapine 4.5 mg tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. Tablets were taken by mouth once daily in the evening.
|
Placebo In-treatment
n=136 participants at risk
Participants took placebo tablets during the 10- to 14-day Placebo Washout Period, placebo tablets during the 6-week In-treatment Period, and placebo tablets during the 1-week Placebo Withdrawal Period. Tablets were taken by mouth once daily in the evening.
|
Esmirtazapine 3.0 mg Follow-up
n=139 participants at risk
After participants received placebo tablets during the Placebo Washout Period and 3.0 mg esmirtazapine during the In-treatment Period, participants were followed for safety up to Day 50 during the Follow-up Period.
|
Esmirtazapine 4.5 mg Follow-up
n=138 participants at risk
After participants received placebo tablets during the Placebo Washout Period and 4.5 mg esmirtazapine during the In-treatment Period, participants were followed for safety up to Day 50 during the Follow-up Period.
|
Placebo Follow-up
n=136 participants at risk
After participants received placebo tablets during the Placebo Washout Period and placebo during the In-treatment Period, participants were followed for safety up to Day 50 during the Follow-up Period.
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
3.6%
5/139 • Number of events 7 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
5.1%
7/138 • Number of events 9 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
6.6%
9/136 • Number of events 11 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
1.4%
2/139 • Number of events 2 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.72%
1/138 • Number of events 1 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.74%
1/136 • Number of events 1 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
|
Nervous system disorders
Somnolence
|
11.5%
16/139 • Number of events 18 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
13.0%
18/138 • Number of events 20 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
2.9%
4/136 • Number of events 4 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/139 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/138 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
0.00%
0/136 • Day 1 to Day 50
Adverse events (AEs) were monitored for All Participants Treated (receiving at least one dose of study drug) during the 6-week In-treatment Period and the subsequent 1-week Follow-up Period. Six participants did not receive study drug and were not included.
|
Additional Information
Senior Vice President, Global Clinical Development Group Leader
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee All publications must be based on data validated and released by the Sponsor. Any such scientific paper, presentation, or other communication concerning the clinical trial will first be submitted to the Sponsor, at least 6 weeks ahead of estimated publication or presentation, for written consent, which shall not be withheld unreasonably.
- Publication restrictions are in place
Restriction type: OTHER