Dyssomnias, Mental Disorders, Sleep Disorders, Sleep Disorders, Intrinsic, Sleep Initiation and Maintenance Disorders
Conditions
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).
Interventions
DRUGesmirtazapine
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Participant flow
Recruitment details
Participants who completed P05701 (Base study NCT00631657) were eligible to enroll on P05721 (Extension study).
Participants by arm
| Arm | Count |
|---|---|
| Esmirtazapine Participants receive esmirtazapine 4.5 mg tablet, orally, once daily (QD) for up to 6 months | 184 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Could not cooperate, unrelated to trial | 4 |
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | Other | 36 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Esmirtazapine |
|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 111 Participants |
| Sex: Female, Male Male | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 59 / 184 |
| serious Total, serious adverse events | 3 / 184 |
Outcome results
Primary
Change From Baseline in Total Sleep Time (TST)
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
Population: The All-Subjects-Treated (AST) population consisted of all participants who received at least one dose of esmertazapine in the extension study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Esmirtazapine | Change From Baseline in Total Sleep Time (TST) | Baseline measure (n=184) | 368.1 Minutes per night | Standard Deviation 91.5 |
| Esmirtazapine | 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
Number of Participants Discontinuing Due to AEs
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
Population: The AST population consisted of all participants who received at least one dose of esmertazapine in the extension study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esmirtazapine | Number of Participants Discontinuing Due to AEs | 9 Participants |
Primary
Number of Participants Experiencing Adverse Events (AEs)
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
Population: The AST population consisted of all participants who received at least one dose of esmertazapine in the extension study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Esmirtazapine | Number of Participants Experiencing Adverse Events (AEs) | 127 Participants |
Secondary
Change From Baseline in Sleep Latency (SL)
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
Population: The All-Subjects-Treated (AST) population consisted of all participants who received at least one dose of esmertazapine in the extension study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Esmirtazapine | Change From Baseline in Sleep Latency (SL) | Baseline measure (n=184) | 38.7 Minutes per night | Standard Deviation 32 |
| Esmirtazapine | 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
Change From Baseline in Wake Time After Sleep Onset (WASO)
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
Population: The AST population consisted of all participants who received at least one dose of esmertazapine in the extension study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Esmirtazapine | Change From Baseline in Wake Time After Sleep Onset (WASO) | Baseline measure (n=184) | 40.0 Minutes per night | Standard Deviation 43.5 |
| Esmirtazapine | 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 |