Trial Outcomes & Findings for Twenty-six Week Extension Trial of Org 50081 (Esmirtazapine) in Outpatients With Chronic Primary Insomnia (176003/P05721/MK-8265-007) (NCT NCT00750919)

Results Overview

TST was defined as the time recorded for sleep diary question 6 "how much time did you actually spend sleeping" as reported by the participants using a LogPad (hand-held electronic data capture device). Baseline was defined as the TST from the last week of the base study. Daily diary data were converted to weekly averages. For each treatment week the non-missing diary data of that week were taken into account; if a treatment week had three non-missing morning diaries or less, the data of the previous week were taken into account, weighing the data of both weeks, using the number of observed diaries as weights (weighted mean); if no diary data were available for a treatment week the data were considered as missing and were not imputed.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

184 participants

Primary outcome timeframe

Baseline and Week 26

Results posted on

2021-02-02

Participant Flow

Participants who completed P05701 (Base study NCT00631657) were eligible to enroll on P05721 (Extension study).

Participant milestones

Participant milestones
Measure	Esmirtazapine Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Overall Study STARTED	184
Overall Study COMPLETED	126
Overall Study NOT COMPLETED	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Esmirtazapine Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Overall Study Adverse Event	9
Overall Study Withdrawal by Subject	1
Overall Study Lack of Efficacy	8
Overall Study Could not cooperate, unrelated to trial	4
Overall Study Other	36

Baseline Characteristics

Twenty-six Week Extension Trial of Org 50081 (Esmirtazapine) in Outpatients With Chronic Primary Insomnia (176003/P05721/MK-8265-007)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Esmirtazapine n=184 Participants Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Age, Continuous	47.8 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	111 Participants n=5 Participants
Sex: Female, Male Male	73 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: The All-Subjects-Treated (AST) population consisted of all participants who received at least one dose of esmertazapine in the extension study.

TST was defined as the time recorded for sleep diary question 6 "how much time did you actually spend sleeping" as reported by the participants using a LogPad (hand-held electronic data capture device). Baseline was defined as the TST from the last week of the base study. Daily diary data were converted to weekly averages. For each treatment week the non-missing diary data of that week were taken into account; if a treatment week had three non-missing morning diaries or less, the data of the previous week were taken into account, weighing the data of both weeks, using the number of observed diaries as weights (weighted mean); if no diary data were available for a treatment week the data were considered as missing and were not imputed.

Outcome measures

Outcome measures
Measure	Esmirtazapine n=184 Participants Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Change From Baseline in Total Sleep Time (TST) Baseline measure (n=184)	368.1 Minutes per night Standard Deviation 91.5
Change From Baseline in Total Sleep Time (TST) Change from baseline at Week 26 (n=123)	9.7 Minutes per night Standard Deviation 56.1

PRIMARY outcome

Timeframe: Up to 30 weeks

Population: The AST population consisted of all participants who received at least one dose of esmertazapine in the extension study.

An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.

Outcome measures

Outcome measures
Measure	Esmirtazapine n=184 Participants Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Number of Participants Experiencing Adverse Events (AEs)	127 Participants

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: The AST population consisted of all participants who received at least one dose of esmertazapine in the extension study.

An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.

Outcome measures

Outcome measures
Measure	Esmirtazapine n=184 Participants Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Number of Participants Discontinuing Due to AEs	9 Participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The All-Subjects-Treated (AST) population consisted of all participants who received at least one dose of esmertazapine in the extension study.

SL was defined as the time recorded for sleep diary question 3 "how long did it take you to fall asleep', " as reported by the participants using a LogPad (hand-held electronic data capture device). Baseline was defined as the SL from the last week of the base study. Daily diary data were converted to weekly averages. For each treatment week the non-missing diary data of that week were taken into account; if a treatment week had three non-missing morning diaries or less, the data of the previous week were taken into account, weighing the data of both weeks, using the number of observed diaries as weights (weighted mean); if no diary data were available for a treatment week the data were considered as missing and were not imputed.

Outcome measures

Outcome measures
Measure	Esmirtazapine n=148 Participants Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Change From Baseline in Sleep Latency (SL) Baseline measure (n=184)	38.7 Minutes per night Standard Deviation 32.0
Change From Baseline in Sleep Latency (SL) Change from baseline at Week 26 (n=123)	-1.5 Minutes per night Standard Deviation 39.1

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The AST population consisted of all participants who received at least one dose of esmertazapine in the extension study.

WASO was defined as the time recorded for sleep diary question 5 "how much time were you awake, after falling asleep initially" as reported by the participants using a LogPad (hand-held electronic data capture device). Baseline was defined as the WASO from the last week of the base study. Daily diary data were converted to weekly averages. For each treatment week the non-missing diary data of that week were taken into account; if a treatment week had three non-missing morning diaries or less, the data of the previous week were taken into account, weighing the data of both weeks, using the number of observed diaries as weights (weighted mean); if no diary data were available for a treatment week the data were considered as missing and were not imputed.

Outcome measures

Outcome measures
Measure	Esmirtazapine n=148 Participants Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Change From Baseline in Wake Time After Sleep Onset (WASO) Baseline measure (n=184)	40.0 Minutes per night Standard Deviation 43.5
Change From Baseline in Wake Time After Sleep Onset (WASO) Change from baseline at Week 26 (n=123)	-5.4 Minutes per night Standard Deviation 32.3

Adverse Events

Esmirtazapine

Serious events: 3 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Esmirtazapine n=184 participants at risk Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Cardiac disorders Acute myocardial infarction	0.54% 1/184 • Number of events 1 • Nonserious AEs were collected from first dispensing of study drug up to 7 days after last dose of study drug. Serious AEs were collected from first dispensing of study drug up to 30 days after last dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.54% 1/184 • Number of events 1 • Nonserious AEs were collected from first dispensing of study drug up to 7 days after last dose of study drug. Serious AEs were collected from first dispensing of study drug up to 30 days after last dose of study drug.
Surgical and medical procedures Strabismus correction	0.54% 1/184 • Number of events 1 • Nonserious AEs were collected from first dispensing of study drug up to 7 days after last dose of study drug. Serious AEs were collected from first dispensing of study drug up to 30 days after last dose of study drug.

Other adverse events

Other adverse events
Measure	Esmirtazapine n=184 participants at risk Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Infections and infestations Nasopharyngitis	10.3% 19/184 • Number of events 20 • Nonserious AEs were collected from first dispensing of study drug up to 7 days after last dose of study drug. Serious AEs were collected from first dispensing of study drug up to 30 days after last dose of study drug.
Investigations Weight increased	6.0% 11/184 • Number of events 12 • Nonserious AEs were collected from first dispensing of study drug up to 7 days after last dose of study drug. Serious AEs were collected from first dispensing of study drug up to 30 days after last dose of study drug.
Nervous system disorders Headache	5.4% 10/184 • Number of events 13 • Nonserious AEs were collected from first dispensing of study drug up to 7 days after last dose of study drug. Serious AEs were collected from first dispensing of study drug up to 30 days after last dose of study drug.
Nervous system disorders Somnolence	5.4% 10/184 • Number of events 11 • Nonserious AEs were collected from first dispensing of study drug up to 7 days after last dose of study drug. Serious AEs were collected from first dispensing of study drug up to 30 days after last dose of study drug.
Psychiatric disorders Insomnia	12.5% 23/184 • Number of events 23 • Nonserious AEs were collected from first dispensing of study drug up to 7 days after last dose of study drug. Serious AEs were collected from first dispensing of study drug up to 30 days after last dose of study drug.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60