Fifty Two Week Extension Trial of Org 50081 (Esmirtazapine) in the Treatment of Insomnia (P05708)

Fifty-Two Weeks, Open Label Extension Trial to Evaluate Safety and Efficacy of Org 50081 in Outpatients With Chronic Primary Insomnia Who Completed Clinical Trial Protocol 176001 or 176002.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00610675

Enrollment

346

Registered

2008-02-08

Start date

2006-12-07

Completion date

2009-08-17

Last updated

2018-10-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Insomnia

Keywords

Fifty two weeks, Open label, extension

Brief summary

This trial is a 52-week, open-label extension trial to investigate safety and to explore efficacy of Org 50081 (Esmirtazapine) in participants who completed Protocol 176001 (P05706) (NCT00482612) or 176002 (P05707) (NCT00506389). Participants who have completed Protocol P05706 or P05707, and are willing to continue treatment with Esmirtazapine, can participate in Protocol 176004 (P05708) after signing informed consent.

Interventions

DRUGOrg 50081

One tablet daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* sign written informed consent after the scope and nature of the investigation have been explained to them, before any trial-related evaluations; * completed Protocol P05706 or P05707; * Have safety and efficacy assessments conducted per protocol P05706 or P05707.

Exclusion criteria

* clinically relevant electrocardiogram (ECG) abnormalities as judged by the investigator; * clinically relevant abnormal laboratory values as judged by the investigator; * any adverse event deemed relevant for exclusion in Protocol P05708 as judged by the investigator or, * were significantly non compliant with protocol criteria and procedures of Protocol P05706 or P05707, as judged by the investigator.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With an Adverse Event	Up to 57 weeks	An Adverse Event (AE) is any untoward occurrence in a participant who is administered any pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding) symptom, or disease temporarily associated with the use of an investigational medicinal product (IMP), whether or not it is related to the IMP.
Number of Participants Who Discontinued Treatment Due to an Adverse Event	Up to 52 weeks	An Adverse Event (AE) is any untoward occurrence in a participant who is administered any pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding) symptom, or disease temporarily associated with the use of an IMP, whether or not it is related to the IMP.

Secondary

Measure	Time frame	Description
Change From Baseline in Wake Time After Sleep Onset at Week 52	Baseline and Week 52	Wake time after sleep onset (WASO) is, if the planned waking time is on or after the time of final awakening, as follows: total time from falling asleep to the time of planned wake up minus the total sleep time. If the planned waking time is before the time of final awakening then WASO is as follows: total time from falling asleep to the time of actual final awakening minus the total sleep time. All times were recorded by the participant in an electronic sleep diary. Baseline values were calculated by averaging baseline values from base trials P05706 and P05707. Data at baseline and at week 52 were collected every morning and evening for 7 consecutive days, and these data were then averaged. Missing values were imputed by the LOCF method, where the last available assessments prior to the scheduled observation were averaged.
Change From Baseline in Number of Awakenings at Week 52	Baseline and Week 52	Number of awakenings is a subjective number recorded by the participant in an electronic sleep diary. Baseline values were calculated by averaging baseline values from base trials P05706 and P05707. Data at baseline and at week 52 were collected every morning and evening for 7 consecutive days, and these data were then averaged. Missing values were imputed by the LOCF method, where the last available assessments prior to the scheduled observation were averaged.
Change From Baseline in Total Sleep Time at Week 52	Baseline and Week 52	Total Sleep Time (TST) is a subjective time recorded by the participant in an electronic sleep diary in response to the question How much time did you actually spend sleeping?. Baseline values were calculated by averaging baseline values from base trials P05706 and P05707. Data at baseline and at week 52 were collected every morning and evening for 7 consecutive days, and these data were then averaged. Missing values were imputed by the last observation carried forward (LOCF) method, where the last available assessments prior to the scheduled observation were averaged.
Change From Baseline in Satisfaction With Sleep Duration Scale at Week 52	Baseline and Week 52	Satisfaction with Sleep Duration is a subjective number on a Visual Analog Scale recorded by the participant in an electronic sleep diary. The scale ranges from 0 to 100, where very unsatisfied is rated at 0, up to fully satisfied, rated at 100. Baseline values were calculated by averaging baseline values from base trials P05706 and P05707. Data at baseline and at week 52 were collected every morning and evening for 7 consecutive days, and these data were then averaged. Missing values were imputed by the LOCF method, where the last available assessments prior to the scheduled observation were averaged.
Change From Baseline in Quality of Sleep Scale at Week 52	Baseline and Week 52	Quality of Sleep is a subjective number on a Visual Analog Scale recorded by the participant in an electronic sleep diary. The scale ranges from 0 to 100, where very poor is rated at 0, up to excellent, rated at 100. Baseline values were calculated by averaging baseline values from base trials P05706 and P05707. Data at baseline and at week 52 were collected every morning and evening for 7 consecutive days, and these data were then averaged. Missing values were imputed by the LOCF method, where the last available assessments prior to the scheduled observation were averaged.
Change From Baseline in Sleep Latency at Week 52	Baseline and Week 52	Sleep Latency (SL) is the time from when the participant went to bed up to the the time the participant actually fell asleep, recorded by the participant in an electronic sleep diary. Baseline values were calculated by averaging baseline values from base trials P05706 and P05707. Data at baseline and at week 52 were collected every morning and evening for 7 consecutive days, and these data were then averaged. Missing values were imputed by the LOCF method, where the last available assessments prior to the scheduled observation were averaged.

Participant flow

Pre-assignment details

Participants who completed base studies P05706 (NCT00482612) and P05707 (NCT00506389) were eligible to enroll in follow-up study P05708

Participants by arm

Arm	Count
Esmirtazapine One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks	342
Total	342

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	67
Overall Study	Insufficient Effect	31
Overall Study	Lack of Compliance	7
Overall Study	Lost to Follow-up	31
Overall Study	Other reason (not specified)	25
Overall Study	Reasons unrelated to trial	27
Overall Study	Untreated	4
Overall Study	Withdrawal by Subject	28

Baseline characteristics

Characteristic	Esmirtazapine
Age, Continuous	46.5 Years STANDARD_DEVIATION 11.5
Sex: Female, Male Female	217 Participants
Sex: Female, Male Male	125 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	118 / 342
serious Total, serious adverse events	8 / 342

Outcome results

Primary

Number of Participants Who Discontinued Treatment Due to an Adverse Event

An Adverse Event (AE) is any untoward occurrence in a participant who is administered any pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding) symptom, or disease temporarily associated with the use of an IMP, whether or not it is related to the IMP.

Time frame: Up to 52 weeks

Population: AST population consisting of all enrolled participants who received at least one dose of trial medication

Arm	Measure	Value (NUMBER)
Esmirtazapine	Number of Participants Who Discontinued Treatment Due to an Adverse Event	67 Participants

Primary

Number of Participants With an Adverse Event

Time frame: Up to 57 weeks

Population: All subjects treated (AST) population consisting of all enrolled participants who received at least one dose of trial medication

Arm	Measure	Value (NUMBER)
Esmirtazapine	Number of Participants With an Adverse Event	235 Participants

Secondary

Change From Baseline in Number of Awakenings at Week 52

Number of awakenings is a subjective number recorded by the participant in an electronic sleep diary. Baseline values were calculated by averaging baseline values from base trials P05706 and P05707. Data at baseline and at week 52 were collected every morning and evening for 7 consecutive days, and these data were then averaged. Missing values were imputed by the LOCF method, where the last available assessments prior to the scheduled observation were averaged.

Time frame: Baseline and Week 52