Trial Outcomes & Findings for Fifty Two Week Extension Trial of Org 50081 (Esmirtazapine) in the Treatment of Insomnia (P05708) (NCT NCT00610675)

NCT ID: NCT00610675

Last Updated: 2018-10-03

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 346 participants
• Primary outcome timeframe: Up to 57 weeks
• Results posted on: 2018-10-03

Participant Flow

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

Participant milestones

Measure	Esmirtazapine One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Overall Study STARTED	346
Overall Study Treated	342
Overall Study COMPLETED	126
Overall Study NOT COMPLETED	220

Reasons for withdrawal

Measure	Esmirtazapine One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Overall Study Untreated	4
Overall Study Adverse Event	67
Overall Study Insufficient Effect	31
Overall Study Withdrawal by Subject	28
Overall Study Reasons unrelated to trial	27
Overall Study Lack of Compliance	7
Overall Study Lost to Follow-up	31
Overall Study Other reason (not specified)	25

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Esmirtazapine n=342 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Age, Continuous	46.5 Years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	217 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 57 weeks

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

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.

Outcome measures

Measure	Esmirtazapine n=342 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Number of Participants With an Adverse Event	235 Participants

PRIMARY outcome

Timeframe: Up to 52 weeks

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

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.

Outcome measures

Measure	Esmirtazapine n=342 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Number of Participants Who Discontinued Treatment Due to an Adverse Event	67 Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: AST participants who received at least one dose of trial medication and provided adequate data entries in their electronic sleep diary

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.

Outcome measures

Measure	Esmirtazapine n=290 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Change From Baseline in Total Sleep Time at Week 52 Baseline (n= 290)	331.7 Minutes Standard Deviation 77.9
Change From Baseline in Total Sleep Time at Week 52 Change from Baseline (n= 285)	73.0 Minutes Standard Deviation 85.9

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: AST participants who received at least one dose of trial medication and provided adequate data entries in their electronic sleep diary

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.

Outcome measures

Measure	Esmirtazapine n=290 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Change From Baseline in Sleep Latency at Week 52 Baseline (n= 290)	70.9 Minutes Standard Deviation 51.3
Change From Baseline in Sleep Latency at Week 52 Change from Baseline (n= 285)	-24.5 Minutes Standard Deviation 62.2

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: AST participants who received at least one dose of trial medication and provided adequate data entries in their electronic sleep diary

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.

Outcome measures

Measure	Esmirtazapine n=290 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Change From Baseline in Wake Time After Sleep Onset at Week 52 Baseline (n= 290)	85.0 Minutes Standard Deviation 58.0
Change From Baseline in Wake Time After Sleep Onset at Week 52 Change from Baseline (n= 285)	-34.8 Minutes Standard Deviation 72.4

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: AST participants who received at least one dose of trial medication and provided adequate data entries in their electronic sleep diary

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.

Outcome measures

Measure	Esmirtazapine n=290 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Change From Baseline in Number of Awakenings at Week 52 Change from Baseline (n= 285)	-0.7 Awakenings Standard Deviation 1.5
Change From Baseline in Number of Awakenings at Week 52 Baseline (n= 290)	2.0 Awakenings Standard Deviation 1.5

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: AST participants who received at least one dose of trial medication and provided adequate data entries in their electronic sleep diary

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.

Outcome measures

Measure	Esmirtazapine n=290 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Change From Baseline in Quality of Sleep Scale at Week 52 Baseline (n= 290)	43.9 Units on a scale Standard Deviation 17.9
Change From Baseline in Quality of Sleep Scale at Week 52 Change from Baseline (n= 285)	17.3 Units on a scale Standard Deviation 22.0

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: AST participants who received at least one dose of trial medication and provided adequate data entries in their electronic sleep diary

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.

Outcome measures

Measure	Esmirtazapine n=290 Participants One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Change From Baseline in Satisfaction With Sleep Duration Scale at Week 52 Baseline (n= 290)	41.3 Units on a scale Standard Deviation 17.8
Change From Baseline in Satisfaction With Sleep Duration Scale at Week 52 Change from Baseline (n= 285)	19.2 Units on a scale Standard Deviation 22.2

Adverse Events

Esmirtazapine

Serious events: 8 serious events

Other events: 118 other events

Deaths: 0 deaths

Serious adverse events

Measure	Esmirtazapine n=342 participants at risk One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Hepatobiliary disorders Biliary colic	0.29% 1/342 • Number of events 1
Hepatobiliary disorders Cholecystitis chronic	0.29% 1/342 • Number of events 1
Infections and infestations Pneumonia	0.29% 1/342 • Number of events 1
Injury, poisoning and procedural complications Road traffic accident	0.29% 1/342 • Number of events 1
Injury, poisoning and procedural complications Skin laceration	0.29% 1/342 • Number of events 2
Injury, poisoning and procedural complications Traumatic shock	0.29% 1/342 • Number of events 1
Musculoskeletal and connective tissue disorders Osteoarthritis	0.29% 1/342 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.29% 1/342 • Number of events 1
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.29% 1/342 • Number of events 1
Respiratory, thoracic and mediastinal disorders Asthma	0.29% 1/342 • Number of events 1
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.29% 1/342 • Number of events 1
Social circumstances Victim of crime	0.29% 1/342 • Number of events 1

Other adverse events

Measure	Esmirtazapine n=342 participants at risk One tablet of Esmirtazapine, 4.5 mg daily for up to 52 weeks
Infections and infestations Nasopharyngitis	7.6% 26/342 • Number of events 27
Infections and infestations Upper respiratory tract infection	5.8% 20/342 • Number of events 24
Investigations Weight increased	13.2% 45/342 • Number of events 50
Nervous system disorders Somnolence	12.9% 44/342 • Number of events 45

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60