Study of the Safety and Effectiveness of Esmirtazapine in Participants With Chronic Primary Insomnia (P05706) (RUBY)

• ClinicalTrials.gov Identifier: NCT00482612
• Recruitment Status: Completed
• First Posted: June 5, 2007
• Results First Posted: July 10, 2014
• Last Update Posted: October 3, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

The purpose of this study is to determine if esmirtazapine (Org 50081) is a safe and effective treatment for insomnia. It was anticipated that esmirtazapine would increase mean Total Sleep Time (TST) as recorded in sleep diaries relative to placebo.

Condition or disease	Intervention/treatment	Phase
Insomnia	Drug: Esmirtazapine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 526 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Two-Week, Double Blind, Placebo-Controlled, Randomized, Parallel Group, Efficacy and Safety Out-Patient Trial With Org 50081 in Patients With Chronic Primary Insomnia
• Actual Study Start Date: December 7, 2006
• Actual Primary Completion Date: August 11, 2008
• Actual Study Completion Date: August 11, 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Esmirtazapine 1.5 mg; Esmirtazapine 1.5 mg tablet, oral administration in the evening, once daily, for 2 weeks	Drug: Esmirtazapine; Esmirtazapine maleate was provided as tablets for oral use containing either 1.5, 3.0, or 4.5 mg of active compound. In addition, tablets contain the following excipients: hydroxypropyl cellulose, maize starch (United States Pharmacopeia [USP] name: corn starch), magnesium stearate, and lactose monohydrate. Tablets were administered orally once daily about 30 minutes prior to bedtime.; Other Names: Org 50081; MK-8265
Experimental: Esmirtazapine 3.0 mg; Esmirtazapine 3.0 mg tablet, oral administration in the evening, once daily, for 2 weeks	Drug: Esmirtazapine; Esmirtazapine maleate was provided as tablets for oral use containing either 1.5, 3.0, or 4.5 mg of active compound. In addition, tablets contain the following excipients: hydroxypropyl cellulose, maize starch (United States Pharmacopeia [USP] name: corn starch), magnesium stearate, and lactose monohydrate. Tablets were administered orally once daily about 30 minutes prior to bedtime.; Other Names: Org 50081; MK-8265
Experimental: Esmirtazapine 4.5 mg; Esmirtazapine 4.5 mg tablet, oral administration in the evening, once daily, for 2 weeks	Drug: Esmirtazapine; Esmirtazapine maleate was provided as tablets for oral use containing either 1.5, 3.0, or 4.5 mg of active compound. In addition, tablets contain the following excipients: hydroxypropyl cellulose, maize starch (United States Pharmacopeia [USP] name: corn starch), magnesium stearate, and lactose monohydrate. Tablets were administered orally once daily about 30 minutes prior to bedtime.; Other Names: Org 50081; MK-8265
Placebo Comparator: Placebo; Placebo to esmirtazapine	Drug: Placebo; Placebo tablets containing the following excipients: hydroxypropyl cellulose, maize starch (USP name: corn starch), magnesium stearate, and lactose monohydrate. Tablets were administered orally once daily about 30 minutes prior to bedtime.

Outcome Measures

Primary Outcome Measures :

1. Average Total Sleep Time (TST) as Recorded Daily in the Sleep Diary During the 14-day In-treatment Period [ Time Frame: Day 1 to Day 15 ]
   TST was defined as the total amount of time (measured in minutes) that was actually spent sleeping the previous night as recorded daily in the participant's sleep diary. TST values over the 14-day active treatment period were averaged for each participant, and average TST was then reported by treatment arm. For participants with missing data, the average of the nights for which TST data were present was used in the analysis.

Secondary Outcome Measures :

1. Average Sleep Latency (SL) as Recorded Daily in the Sleep Diary During the 14-day In-treatment Period [ Time Frame: Day 1 to Day 15 ]
   SL was defined as the duration of time measured in minutes that it took a participant to fall asleep as recorded daily in the participant's sleep diary. SL values over the 14-day active treatment period were averaged for each participant, and average SL was then reported by treatment arm. For participants with missing data, the average of the nights for which TST data were present were used in the analysis.
2. Number of Participants Experiencing an Adverse Event (AE) During the 14-day In-treatment Period [ Time Frame: Day 1 to Day 15 ]
   The total number of participants with an AE during the 14-day In-treatment Period was tallied for each treatment arm. An AE was defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
3. Number of Participants Who Discontinued From Study Treatment Due to an AE During the 14-day In-Treatment Period [ Time Frame: Day 1 to Day 15 ]
   The total number of participants discontinuing from study treatment due to experiencing an AE was tallied for each treatment arm. An AE was defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Has signed written informed consent after the scope and nature of the investigation was explained to them
• Has difficulty falling asleep, maintaining sleep or has early morning awakenings

Exclusion Criteria:

• Significant medical or psychiatric illness causing sleep disturbances
• Has a history of bipolar disorder or family (immediate family) of suicide
• Has sleep disorder such as sleep related breathing disorder, restless leg syndrome, narcolepsy
• Has significant other medical illness such as acute or chronic pain, heart, kidney or liver disease within the last year
• Currently diagnosed or meets the criteria for Major Depressive Disorder (MDD) or has been treated for MDD with the last 2 years
• Substance abuse, excessive use of alcohol (as determined by the physician) or drug addiction within the last year.

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

Ivgy-May N, Roth T, Ruwe F, Walsh J. Esmirtazapine in non-elderly adult patients with primary insomnia: efficacy and safety from a 2-week randomized outpatient trial. Sleep Med. 2015 Jul;16(7):831-7. doi: 10.1016/j.sleep.2015.03.005. Epub 2015 Mar 30.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00482612
• Other Study ID Numbers: P05706; 176001 ( Other Identifier: Protocol number ); MK-8265-003 ( Other Identifier: Protocol number )
• First Posted: June 5, 2007
• Results First Posted: July 10, 2014
• Last Update Posted: October 3, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Sleep Initiation and Maintenance Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Mirtazapine; Antidepressive Agents; Psychotropic Drugs; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Serotonin 5-HT3 Receptor Antagonists