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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00750919
• Collaborator: (none)
• Enrollment: 184
• Arm: 1
• Actual Duration (Months): 17.1

Study Details

Study Description

Brief Summary

This trial is a 26-week, open label extension trial to investigate safety and explore efficacy of esmertazapine in participants with insomnia who completed protocol 21106/P05701/MK-8265-002 (NCT00631657).

Condition or Disease	Intervention/Treatment	Phase
Sleep Initiation and Maintenance Disorders; Mental Disorders; Dyssomnias; Sleep Disorders; Sleep Disorders, Intrinsic	Drug: esmirtazapine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 184 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Twenty-six Weeks, Open-label Extension Trial to Evaluate Safety and Efficacy of Org 50081 (Esmirtazapine) in Outpatients With Chronic Primary Insomnia Who Completed Clinical Trial Protocol 21106
• Actual Study Start Date: Oct 7, 2008
• Actual Primary Completion Date: Mar 10, 2010
• Actual Study Completion Date: Mar 10, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Esmirtazapine Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months.	Drug: esmirtazapine

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Total Sleep Time (TST) [Baseline and Week 26]

   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.

2. Number of Participants Experiencing Adverse Events (AEs) [Up to 30 weeks]

   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.

3. Number of Participants Discontinuing Due to AEs [Up to 26 weeks]

   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.

Secondary Outcome Measures

1. Change From Baseline in Sleep Latency (SL) [Baseline and Week 26]

   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.

2. Change From Baseline in Wake Time After Sleep Onset (WASO) [Baseline and Week 26]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Sign written informed consent

• Completed clinical trial 21106/P05701/MK-8265-002

Exclusion Criteria:

• Any (serious) adverse event, medical condition or required concomitant medication deemed relevant for exclusion in trial 21106/P05071/MK-8265-002 as judged by the investigator

• Were significantly non compliant with protocol criteria and procedures of trial 21106/P05701/MK-8265-002, as judged by the investigator

• Pregnancy

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00750919
• Other Study ID Numbers: P05721; 176003; 2007-005237-10
• First Posted: Sep 11, 2008
• Last Update Posted: Feb 2, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Parasomnias; Dyssomnias; Sleep Disorders, Intrinsic; Disease; Mental Disorders; Mirtazapine

Study Results

Participant Flow

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

Arm/Group Title	Esmirtazapine
Arm/Group Description	Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Period Title: Overall Study
STARTED	184
COMPLETED	126
NOT COMPLETED	58

Baseline Characteristics

Arm/Group Title	Esmirtazapine
Arm/Group Description	Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Overall Participants	184
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.8 (11.5)
Sex: Female, Male (Count of Participants)
Female	111 60.3%
Male	73 39.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Total Sleep Time (TST)
Description	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.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Esmirtazapine
Arm/Group Description	Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Measure Participants	184
Baseline measure (n=184)	368.1 (91.5)
Change from baseline at Week 26 (n=123)	9.7 (56.1)

2. Secondary Outcome

Title	Change From Baseline in Sleep Latency (SL)
Description	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.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Esmirtazapine
Arm/Group Description	Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Measure Participants	148
Baseline measure (n=184)	38.7 (32.0)
Change from baseline at Week 26 (n=123)	-1.5 (39.1)

3. Secondary Outcome

Title	Change From Baseline in Wake Time After Sleep Onset (WASO)
Description	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.
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Esmirtazapine
Arm/Group Description	Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Measure Participants	148
Baseline measure (n=184)	40.0 (43.5)
Change from baseline at Week 26 (n=123)	-5.4 (32.3)

4. Primary Outcome

Title	Number of Participants Experiencing Adverse Events (AEs)
Description	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.
Time Frame	Up to 30 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Esmirtazapine
Arm/Group Description	Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Measure Participants	184
Number [Participants]	127 69%

5. Primary Outcome

Title	Number of Participants Discontinuing Due to AEs
Description	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.
Time Frame	Up to 26 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Esmirtazapine
Arm/Group Description	Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
Measure Participants	184
Number [Participants]	9 4.9%

Adverse Events

Time Frame	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.
Arm/Group Title	Esmirtazapine
Arm/Group Description	Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months
All Cause Mortality
	Esmirtazapine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Esmirtazapine
	Affected / at Risk (%)	# Events
Total	3/184 (1.6%)
Cardiac disorders
Acute myocardial infarction	1/184 (0.5%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	1/184 (0.5%)	1
Surgical and medical procedures
Strabismus correction	1/184 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Esmirtazapine
	Affected / at Risk (%)	# Events
Total	59/184 (32.1%)
Infections and infestations
Nasopharyngitis	19/184 (10.3%)	20
Investigations
Weight increased	11/184 (6%)	12
Nervous system disorders
Headache	10/184 (5.4%)	13
Somnolence	10/184 (5.4%)	11
Psychiatric disorders
Insomnia	23/184 (12.5%)	23

Limitations/Caveats

This study was terminated due to the Sponsor's decision not to continue development of esmertazapine for this indication.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only 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 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.