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Orvepitant MDD: A Randomised, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Orvepitant in Subjects With Major Depressive Disorder

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Terminated
CT.gov ID
NCT00880048
Collaborator
(none)
343
Enrollment
32
Locations
3
Arms
15.3
Actual Duration (Months)
10.7
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a 6-week, randomised, multicenter, double-blind, placebo controlled, fixed dose parallel group study to assess the efficacy and safety of orvepitant (30 and 60 mg/day) versus placebo in subjects with a diagnosis of a Major Depressive Disorder, whose symptoms are considered moderate or severe.

Following an initial screening visit, subjects fulfilling the study inclusion and exclusion criteria will enter a pre-treatment screening phase to permit evaluation of the laboratory and ECG assessments and to confirm eligibility for inclusion into the study. This screening phase will be a minimum of 7 days, but no longer than 21 days. At the completion of the screening period, eligible subjects will be randomised at the baseline visit to receive either orvepitant 30mg/day, orvepitant 60mg/day or placebo (equal chance of receiving any of the three possible treatments, i.e., a 1:1:1 ratio) for a six-week double-blind treatment phase. Those subjects randomised to receive placebo will receive study medication identical in appearance to that received by subjects assigned to receive orvepitant 30 or 60mg/day.

Efficacy will be assessed via standard depression symptom and severity rating scales or questionaires. The Hamilton Depression Rating Scale (HAM-D) will be used as the primary measure. Secondary efficacy endpoints include the Quick Inventory of Depressive Symptomatology (QIDS-SR) and the Clinical Global Impression- Global Improvement and Severity of Illness Scale (CGI-I and CGI-S, respectively).

Safety will be assessed by monitoring for adverse events (side effects) and through periodic laboratory evaluations (blood tests), vital signs assessments (e.g., blood pressure, heart rate, temperature) and heart function measurements (electrocardiograms, or ECGs).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The purpose of the current study is to test the safety and the anti-depressant effects of orvepitant, an investigational antidepressant. Efficacy will be assessed using standard depression symptom and severity rating scales (questionaires). The Hamilton Depression Rating Scale (HAM-D) will serve as the primary measure of efficacy, and . Secondary efficacy endpoints include the Bech Melancholia Scale (sum of items 1, 2, 7, 8, 10, and 13 of the 17-item HAM-D scale), the Quick Inventory of Depressive Symptomatology (QIDS-SR), the Clinical Global Impression- Global Improvement and Severity of Illness Scale (CGI-I and CGI-S, respectively), the HAM-D anxiety factor score (sum of items 10, 11, 12, 13, 15 and 17), the Cognitive and Physical Function Questionnaire (CPFQ) and a morning sleep questionnaire.

Safety and tolerability will be assessed by monitoring adverse events (AEs or side effects), physical examinations (including vital signs such as blood pressure and heart rate), clinical laboratory assessments (blood tests), electrical recordings of the heart (electrocardiograms or ECG's), the Columbia Suicidality Severity Rating Scale (CSSRS), Sexual Function Questionnaire (SFQ), and weight change.

Blood samples will be taken at different time points to assess blood levels of orvepitant in patients, allowing the relationship between amount of orvepitant in the body and efficacy to be studied.

The primary objective of the study is to evaluate the antidepressant efficacy of orvepitant (30 and 60mg/day) versus placebo (a "sugar pill", with no active ingredients). The secondary objectives include assessing the safety and tolerability of orvepitant, assessing the profile of appearance and disappearance of orvepitant in the body (blood) following administration (i.e., assessing how long the drug remains in the body), and lastly to examine the relationship between blood levels of the drug and efficacy (i..e, the change in HAM-D total score relative to what it was before starting the study medication.

Following an initial screening visit, subjects fulfilling the study entrance criteria will enter a pre-treatment screening phase to permit evaluation of the laboratory and electrocardiogram assessments and to confirm eligibility for inclusion into the study. This screening phase will be a minimum of 7 days, but no longer than 21 days. During the screening period and the treatment phase if the study, if the subject is selected for study entry, subjects will undergo assessments of their depressive symptoms via a face-to-face interview as well as via a video-based system (i.e., live subject interview conducted by an off-site interviewer using a web-based video camera). Upon completion of the screening period, eligible subjects will be randomly assigned at the baseline visit to one of three treatment regimens: orvepitant 30mg/day, orvepitant 60mg/day or placebo for a six-week treatment phase. The chances of receiving each of the three possible treatments will be equal. Orvepitant will be administered as tablets. Those subjects randomised to receive placebo will receive study medication identical in appearance to that received by subjects assigned to receive orvepitant.

During the treatment phase, subjects will be required to return to the clinic at the end of Weeks 1, 2, 4 and 6. In addition, all subjects will be required to return for a follow-up visit 14 days after the last dose of study medication. In addition, all subjects with ongoing adverse events at the 14-day follow-up visit will be required to return for a further follow-up visit 28 days after the last dose of study medication.

Male and female outpatients between the ages of 18 to 64 years inclusive with a primary diagnosis of Major Depressive Disorder will be enrolled into this study. A total of approximately 350 subjects are expected to be enrolled at approximately 30 different study sites in the U.S. and Canada.

Study Design

Study Type:
Interventional
Actual Enrollment :
343 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomised, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Orvepitant in Subjects With Major Depressive Disorder
Actual Study Start Date :
Mar 11, 2009
Actual Primary Completion Date :
Jun 21, 2010
Actual Study Completion Date :
Jun 21, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: orvepitant 30 mg

orvepitant 30 mg (low dose)

Drug: orvepitant
neurokinin-1 antagonist
Other Names:
  • GW823296

    		•
    Experimental: orvepitant 60 mg

    orvepitant 60 mg (high dose)

    Drug: orvepitant
    neurokinin-1 antagonist
    Other Names:
  • GW823296

    		•
    Placebo Comparator: Placebo

    inactive placebo to match orvepitant 30 mg and 60 mg dosage forms

    Other: Placebo
    Placebo to match orvepitant 30 mg and 60 mg

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) Total Score [Baseline and up to Week 6]

      HAM-D was use to measure the severity of depressive symptoms in participants with primary depressive illness. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. Items with quantifiable severity were scored 0 (lowest severity) to 4 (greatest severity); The HAM-D total score was calculated by summing the individual response scores. The lowest possible score was 0 (absence of depression) and the highest possible score was 52 (most severe measure of depression). For the last observation carried forward analyses, the most recent post randomization total score (as opposed to individual responses) was "carried forward" and used in the calculation of the change from randomization (Baseline) value. If the responses to more than 1 question were missing for a participant at a particular time point, the total score was not calculated. Change from Baseline in total score was the difference between HAM-D total score at the time point being analyzed and randomization.

    Secondary Outcome Measures

    1. Percentage of Participants With a >=50% Reduction From Baseline in HAM-D Total Score [Up to Week 6]

      HAM-D was use to measure the severity of depressive symptoms in participants with primary depressive illness. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. The HAM-D Total Score was calculated by summing the individual response scores. The lowest possible score was 0 (absence of depression) and the highest possible score was 52 (most severe measure of depression). For the last observation carried forward analyses, the most recent post randomization total score (as opposed to individual responses) was "carried forward" and used in the calculation of the change from randomization value. If the responses to more than 1 question were missing for a participant at a particular time point, the total score was not calculated. Data was presented as percent of HAM-D responders which was defined as participants who has a >=50% reduction from randomization in HAM-D total score.

    2. Number of Participants Who Maintained Clinical Response by Week 6 [Up to Week 6]

      The start of the 'maintained antidepressant response' was the time at which a participant demonstrates a 50% reduction from randomization in their HAM-D total score and where this response was maintained until the end of the treatment phase (week 6). Participants who met the 50% reduction at week 6 without having met it at week 4 were considered to have reached a maintained response, and therefore were censored at week 6. Where a participant met the criteria for maintained antidepressant response, the "time (in days) to maintained antidepressant response" was calculated as: (Date of assessment at which the maintained response commences minus Date of randomization) plus 1. Where a participant did not met the criteria for maintained antidepressant response, their time to response was censored at the last on-treatment assessment they undertake, up to and including the week 6 assessment.

    3. Change From Baseline in the Bech Melancholia Scale Total Score (Sum of Items 1, 2, 7, 8, 10, and 13 of the 17-item HAM-D Scale) [Baseline and up to Week 6]

      The BECH scale was extracted from the HAMD-17 and comprised the 6 items (sum of items 1, 2, 7, 8, 10, and 13 of the 17-item HAM-D scale): Depressed Mood, Feelings of Guilt, Work and Activities, Retardation, Anxiety Psychic and Somatic Symptoms General. The BECH Total Score was calculated by summing the individual response scores. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. The lowest possible score was 0 (absence of depression) and the highest possible score was 22 (most severe measure of depression). Due to the small number of items , missing data was not imputed for the BECH Total Score. If any of the 6 items above were missing, the total score was not calculated at that visit. Value at randomization was the Baseline value. Change from Baseline in BECH Total Score was the difference between BECH Total Score at the time point being analyzed to randomization.

    4. Change From Baseline in the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR 16) Total Score [Baseline and up to Week 6]

      QIDS-SR assessed symptoms severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criterion for major depressive disorder. It consisted of 16 separate items, defining 9 DSM-IV symptom criterion domains. A total score was obtained by summing scores on each domain. The lowest possible score was 0, which represented an absence of depression; the highest possible score was 27, which represented the most severe measure of depression. Due to the small number of items, missing data was not imputed for the QIDS-SR total score. If any of the 9 domains above were missing, the total score was not calculated at that visit. Value at randomization was the Baseline value. Change from Baseline in total score was the difference between QIDS total score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.

    5. Change From Baseline in the HAM-D Anxiety Factor Score (Sum of Items 10, 11, 12, 13, 15 and 17) [Baseline and up to Week 6]

      The anxiety score was extracted from the HAM-D-17 and comprises of items 10, 11, 12, 13 and 15 from the HAM-D scale. The anxiety score was calculated by summing the individual response scores to these questions. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. The lowest possible score was 0 (absence of depression) and the highest possible score was 18 (most severe measure of depression). Due to the small number of items, missing data was not imputed for the anxiety score. If either of the anxiety items was missing, the total score was not calculated at that visit. Value at randomization was the Baseline value. Change from Baseline in anxiety score was the difference between the anxiety score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.

    6. Percentage of Participants With Clinical Global Impression- Global Improvement (CGI-I) Score [Up to Week 6]

      The CGI-I assessed scores range from 1 - Very much Improved to 7 - Very much worse, with 0 representing a participant that was not assessed. The assessed scores were dichotomized. Scores of 1 or 2 was in the first category, scoring 1. All other scores (except zero which was regarded as missing) was in the second category, scoring 0. The percentage of participants in the first category was calculated for each assessment.

    7. Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-S) Score [Baseline and up to Week 6]

      The CGI-S assessed scores range from 1 - Very much Improved to 7 - Very much worse, with 0 representing a participant that was not assessed. For the CGI-S, remote, blinded MedAvante, raters assessed the participant's severity of illness considering their total clinical experience with the particular population being studied and information obtained during the Baseline HAMD interview with the participant. Value at randomization was the Baseline value. Change from Baseline in total score was the difference between CGI-S Score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.

    8. Change From Baseline in the Cognitive and Physical Function Questionnaire (CPFQ) Total Score [Baseline and up to Week 6]

      CPFQ was a brief self-report scale which was designed to measure cognitive and executive dysfunction in mood and anxiety disorders. The CPFQ comprised of 7 questions assessing each of the most common complaints of depressed participants reporting fatigue or cognitive/executive problems. Each question was rated on a scale of 1 to 6, with 1 indicating greater than normal functioning, 2, indicating normal functioning, and with higher numbers indicating poorer functioning. Two versions of the CPFQ were utilized during the study. The Baseline CPFQ requested the participant reflect back over the past month. For the treatment period, the CPFQ requested the participant reflect back over the past week. Value at randomization was the Baseline value. Change from Baseline in Total Score was the difference between CPFQ Score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.

    9. Change From Baseline in Morning Sleep Questionnaire (MSQ) Total Sleep Time, Sleep Onset Latency and Wake Time After Sleep Onset [Baseline and up to Week 6]

      The MSQ was a self-rated scale designed to assess effects on sleep and effects on next day functioning. The following variables were assessed in order to determine effects on sleep: total sleep time, sleep onset latency, number of nocturnal awakenings, wake time after sleep onset and sleep quality (from poor, assigned a score of 1, to excellent, assigned a score of 10). The refreshing value of the sleep was also determined (poor assigned a score of 1, to excellent, assigned a score of 10). Value at randomization was the Baseline value. Change from Baseline was calculated for each domain separately. Change from Baseline was the difference between score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.

    10. Change From Baseline in the MSQ Number of Nocturnal Awakenings [Baseline and upto Week 6]

      The MSQ was a self-rated scale designed to assess effects on sleep and effects on next day functioning. The following variables were assessed in order to determine effects on sleep: total sleep time, sleep onset latency, number of nocturnal awakenings, wake time after sleep onset and sleep quality (from poor, assigned a score of 1, to excellent, assigned a score of 10). The refreshing value of the sleep was also determined (poor assigned a score of 1, to excellent, assigned a score of 10). Value at randomization was the Baseline value. Change from Baseline was calculated for each domain separately. Change from Baseline was the difference between score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.

    11. Change From Baseline in the MSQ Sleep Quality and Refreshing Value of Sleep [Baseline and up to Week 6]

      The MSQ was a self-rated scale designed to assess effects on sleep and effects on next day functioning. The following variables were assessed in order to determine effects on sleep: total sleep time, sleep onset latency, number of nocturnal awakenings, wake time after sleep onset and sleep quality (from poor, assigned a score of 1, to excellent, assigned a score of 10). The refreshing value of the sleep was also determined (poor assigned a score of 1, to excellent, assigned a score of 10). Value at randomization was the Baseline value. Change from Baseline was calculated for each domain separately. Change from Baseline was the difference between score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.

    12. Number of HAM-D Remitters [Up to Week 6]

      A HAMD remitter was defined as a participant who had a HAMD Total Score <=7. The HAMD total score was calculated for each participant at each time point. Those participants with no missing value for HAMD total score were categorized as having a HAMD total score of <=7 or >7.

    13. Number of Participants With Suicide-Related Events Based on the Columbia Suicidality Severity Rating Scale (CSSRS) [Up to 17 days post-treatment]

      Assessment of suicidality were done through use of the CSSRS for suicidal ideation and suicidal behavior. For suicidal ideation ratings were 1 to 5, where 1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation without intent to act, 4. Active suicidal ideation with any methods (not plan) without intent to act, 5. Active suicidal ideation with specific plan and intent and for suicidal behavior ratings were 6 to 12, Where 6. Actual attempt, 7. Engaged in non-suicidal self-injurious behavior, 8. Interrupted attempt, 9. Aborted attempt, 10. Preparatory acts or behavior, 11. Suicidal behavior, 12. Completed suicide. n= number participants with at least one CSSRS assessment after the first dose of study medication (i.e. on treatment or post treatment). Only those categories from CSSRS (1-12) are presented for which symptoms were actually observed in the participants. Categories with null values for all the arms have not been presented.

    14. Number of Incidences of Discontinuation Emergent Signs and Symptoms Using the Discontinuation-Emergent Signs and Symptoms (DESS) [Up to 17 days post-treatment]

      The DESS scale consisted of 43 signs and symptoms, scored as 'new symptom', 'old symptom but worse', 'old symptom but improved' or 'symptom not present/old symptom but unchanged'. The total number of new signs and symptoms, old symptoms but worse, old symptoms but improved and the total number of new or old-but-worse signs and symptoms were calculated for each treatment and visit. n = number of subjects who had at least one of the 43 symptoms in the specified category. The summary for a specified category are of the number of symptoms the n subjects had in that category. Treatment period was up to Week 6.

    15. Change From Baseline in the Massachusetts Sexual Function Questionnaire (MSFQ) Total Score in Males [Baseline and up to Week 6]

      MSFQ included five items with a score ranging from 1 to 6 (1 = greater than normal; 2 = normal; 3 = minimally diminished; 5 = markedly diminished; and 6 = totally absent). The following areas of sexual functioning were included: diminished/absent libido; arousal difficulties; orgasm difficulties/anorgasmia; erectile dysfunction (males only) and degree of sexual satisfaction. A total score was used as a global measure of sexual dysfunction. The Baseline MSFQ requested the participant reflect back over the past month. For the treatment period, the follow-up MSFQ requested the participant reflect back over the past week. Change from Baseline was the value at post-Baseline visit minus Baseline value.

    16. Change From Baseline in the MSFQ Total Score in Females [Baseline and up to Week 6]

      MSFQ included five items with a score ranging from 1 to 6 (1 = greater than normal; 2 = normal; 3 = minimally diminished; 5 = markedly diminished; and 6 = totally absent). The following areas of sexual functioning were included: diminished/absent libido; arousal difficulties; orgasm difficulties/anorgasmia; erectile dysfunction (males only) and degree of sexual satisfaction. A total score was used as a global measure of sexual dysfunction. The Baseline MSFQ requested the participant reflect back over the past month. For the treatment period, the follow-up MSFQ requested the participant reflect back over the past week. Change from Baseline was the value at post-Baseline visit minus Baseline value.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 64 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Subjects must have the ability to comprehend the Informed Consent Form.

    • Male or female outpatients, aged 18-64, inclusive.

    • A primary diagnosis of major depressive disorder, single episode or recurrent.

    • Subjects must, in the investigator's opinion and based on the subject's history, have met depression criteria for at least 8 weeks prior to the Screening Visit.

    • Subjects with symptom severity considered to be at least moderate to severe by the investigator.

    • Women of childbearing potential are only eligible IF they commit to consistent and correct use of an acceptable method of birth control that must be documentation at each visit

    Exclusion Criteria:

    • Subjects whose mood-related symptoms are better accounted for by a diagnosis other than depression; subjects diagnosed with Alzheimer's Disease or other form of dementia; subjects diagnosed with a current/recent eating disorder such as anorexia nervosa or bulimia; subjects with a diagnosed history of schizophrenia, schizoaffective disorder, or Bipolar Disorder.

    • Subjects with any history of a significant abnormality of the neurological system (including dementia and other cognitive disorders or significant head injury) or any history of seizures (convulsions).

    • Subjects have a positive urine test at screening for illegal drug use and/or who have a history of substance abuse or dependence (alcohol or drugs) within the past 12 months.

    • Subjects who are currently receiving regularly scheduled psychotherapy (individual or group), plan to start psychotherapy during the trial or have received regularly scheduled psychotherapy during the 12 week period prior to the Screening Visit.

    • Subjects who have a history of failing to respond to adequate treatment with an antidepressant, i..e, failure to improve following administration of at least two other antidepressants, each given for at least 4 weeks.

    • Subjects who, in the investigator's judgement, pose a homicidal or serious suicidal risk, have made a suicide attempt within the 6 months preceding screening or who have ever been homicidal.

    • Subjects who have received the following treatments for depression in the past: electroconvulsive therapy (ECT), vagal stimulation, or transcranial magnetic stimulation (TMS) within the 6 months prior to the Screening Visit.

    • Subjects with an unstable medical disorder; or with a disorder that otherwise would likely interfere with the activity of the study medication (orvepitant).

    • Subjects have any screening laboratory abnormality that in the investigator's judgement is considered to be clinically significant.

    • Subjects with an abnormal thyroid test at the Screening Visit. Subjects maintained on thyroid medication must have normal thyroid levels for a period of at least six months prior to the Screening Visit.

    • Subjects have any screening electrocardiography (ECG) finding that in the investigator's judgement is considered to be clinically significant.

    • Women who have a positive pregnancy test at the Screening Visit, a positive urine dipstick test at the Baseline (Randomization) Visit, or who are lactating or planning to become pregnant within the 4 months following the Screen Visit.

    • Subjects who have taken other psychoactive drugs within two weeks prior to the Baseline Visit i.e. at any time during the Screening period. This includes "over-the-counter" psychoactive medications such as St. John's Wort and SAM-e.

    • Subjects who have taken other drugs within 2 weeks prior to the Baseline visit which the investigator feels may interact with the study medication.

    • Subjects who are currently participating in another clinical trial in which the subject is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month for studies unrelated to depression, or 6 months for studies related to depression.

    • Subjects who have no contact with an adult on a daily basis. This would exclude subjects who are not living with at least one other adult or subjects who do not have an adult who contacts them on a daily basis.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 GSK Investigational Site Phoenix Arizona United States 85020
    2 GSK Investigational Site Little Rock Arkansas United States 72223
    3 GSK Investigational Site Orange California United States 92868
    4 GSK Investigational Site Denver Colorado United States 80239
    5 GSK Investigational Site Norwich Connecticut United States 06360
    6 GSK Investigational Site Jacksonville Florida United States 32216
    7 GSK Investigational Site Orlando Florida United States 32806
    8 GSK Investigational Site Winter Park Florida United States 32789
    9 GSK Investigational Site Springfield Illinois United States 62711
    10 GSK Investigational Site Rockville Maryland United States 20852
    11 GSK Investigational Site Weymouth Massachusetts United States 02190
    12 GSK Investigational Site Saint Charles Missouri United States 63301
    13 GSK Investigational Site Willingboro New Jersey United States 08046
    14 GSK Investigational Site Brooklyn New York United States 11235
    15 GSK Investigational Site Dayton Ohio United States 45408
    16 GSK Investigational Site Garfield Heights Ohio United States 44125
    17 GSK Investigational Site Portland Oregon United States 97210
    18 GSK Investigational Site Salem Oregon United States 97301
    19 GSK Investigational Site Emmaus Pennsylvania United States 18049
    20 GSK Investigational Site Philadelphia Pennsylvania United States 19131
    21 GSK Investigational Site Philadelphia Pennsylvania United States 19139
    22 GSK Investigational Site Columbia South Carolina United States 29201
    23 GSK Investigational Site Austin Texas United States 78756
    24 GSK Investigational Site Dallas Texas United States 75231
    25 GSK Investigational Site San Antonio Texas United States 78229-3815
    26 GSK Investigational Site Charlottesville Virginia United States 22903
    27 GSK Investigational Site Milwaukee Wisconsin United States 53226
    28 GSK Investigational Site Penticton British Columbia Canada V2A 4M4
    29 GSK Investigational Site Miramichi New Brunswick Canada E1V 6X3
    30 GSK Investigational Site Sydney Nova Scotia Canada B1S 2E8
    31 GSK Investigational Site Mississauga Ontario Canada L5M 4N4
    32 GSK Investigational Site Gatineau Quebec Canada J9A 1K7

    Sponsors and Collaborators

    • GlaxoSmithKline

    Investigators

    • Study Director: GSK Clinical Trials, GlaxoSmithKline

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    GlaxoSmithKline
    ClinicalTrials.gov Identifier:
    NCT00880048
    Other Study ID Numbers:
    • 110833
    First Posted:
    Apr 13, 2009
    Last Update Posted:
    Oct 13, 2017
    Last Verified:
    Aug 1, 2017
    Keywords provided by GlaxoSmithKline
    depression
    safety
    HAMD
    QIDS-SR
    NK-1 antagonist
    efficacy
    orvepitant
    placebo
    MDD
    video-rating
    Additional relevant MeSH terms:
    Depressive Disorder
    Depression
    Depressive Disorder, Major

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 31 centers across the North America (27 centers in United States of America and 4 centers in Canada) during the period 06 April 2009 to 21 June 2010. Total of 1604 participants were screened for study eligibility, of which 343 participants were randomized into the study.
    Pre-assignment Detail A total of 339 participants were included in Intent-to-treat (ITT) population. ITT population comprised of all participants who gave informed consent, were randomized, received at least one dose of double blind medication and for whom at least one post-randomization assessment was available.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Period Title: Overall Study
    STARTED 116 115 112
    COMPLETED 88 82 77
    NOT COMPLETED 28 33 35

    Baseline Characteristics

    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg Total
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks. Total of all reporting groups
    Overall Participants 116 115 112 343
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    41.7
    (10.61)
    40.4
    (11.35)
    43.1
    (10.66)
    41.7
    (10.90)
    Sex: Female, Male (Count of Participants)
    Female
    68
    58.6%
    75
    65.2%
    73
    65.2%
    216
    63%
    Male
    48
    41.4%
    40
    34.8%
    39
    34.8%
    127
    37%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    0.9%
    0
    0%
    1
    0.3%
    Asian
    3
    2.6%
    3
    2.6%
    1
    0.9%
    7
    2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.9%
    0
    0%
    1
    0.3%
    Black or African American
    32
    27.6%
    24
    20.9%
    33
    29.5%
    89
    25.9%
    White
    78
    67.2%
    83
    72.2%
    76
    67.9%
    237
    69.1%
    More than one race
    2
    1.7%
    2
    1.7%
    2
    1.8%
    6
    1.7%
    Unknown or Not Reported
    1
    0.9%
    1
    0.9%
    0
    0%
    2
    0.6%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) Total Score
    Description HAM-D was use to measure the severity of depressive symptoms in participants with primary depressive illness. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. Items with quantifiable severity were scored 0 (lowest severity) to 4 (greatest severity); The HAM-D total score was calculated by summing the individual response scores. The lowest possible score was 0 (absence of depression) and the highest possible score was 52 (most severe measure of depression). For the last observation carried forward analyses, the most recent post randomization total score (as opposed to individual responses) was "carried forward" and used in the calculation of the change from randomization (Baseline) value. If the responses to more than 1 question were missing for a participant at a particular time point, the total score was not calculated. Change from Baseline in total score was the difference between HAM-D total score at the time point being analyzed and randomization.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    -2.85
    (0.454)
    -4.45
    (0.462)
    -5.11
    (0.470)
    Week 2
    -4.35
    (0.531)
    -5.92
    (0.545)
    -6.00
    (0.565)
    Week 4
    -6.87
    (0.672)
    -8.68
    (0.691)
    -8.90
    (0.703)
    Week 6
    -8.29
    (0.727)
    -9.95
    (0.754)
    -9.05
    (0.777)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0133
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.60
    Confidence Interval (2-Sided) 95%
    -2.87 to -0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0006
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -2.26
    Confidence Interval (2-Sided) 95%
    -3.54 to -0.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0394
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.57
    Confidence Interval (2-Sided) 95%
    -3.06 to -0.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0332
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.65
    Confidence Interval (2-Sided) 95%
    -3.16 to -0.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0601
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.82
    Confidence Interval (2-Sided) 95%
    -3.71 to 0.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0369
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -2.03
    Confidence Interval (2-Sided) 95%
    -3.94 to -0.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1122
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.67
    Confidence Interval (2-Sided) 95%
    -3.73 to 0.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 6
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4713
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.76
    Confidence Interval (2-Sided) 95%
    -2.85 to 1.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants With a >=50% Reduction From Baseline in HAM-D Total Score
    Description HAM-D was use to measure the severity of depressive symptoms in participants with primary depressive illness. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. The HAM-D Total Score was calculated by summing the individual response scores. The lowest possible score was 0 (absence of depression) and the highest possible score was 52 (most severe measure of depression). For the last observation carried forward analyses, the most recent post randomization total score (as opposed to individual responses) was "carried forward" and used in the calculation of the change from randomization value. If the responses to more than 1 question were missing for a participant at a particular time point, the total score was not calculated. Data was presented as percent of HAM-D responders which was defined as participants who has a >=50% reduction from randomization in HAM-D total score.
    Time Frame Up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    4
    3.4%
    7
    6.1%
    10
    8.9%
    Week 2
    9
    7.8%
    14
    12.2%
    13
    11.6%
    Week 4
    22
    19%
    27
    23.5%
    29
    25.9%
    Week 6
    27
    23.3%
    37
    32.2%
    30
    26.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2232
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.15
    Confidence Interval (2-Sided) 95%
    0.63 to 7.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0559
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.15
    Confidence Interval (2-Sided) 95%
    0.97 to 10.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3395
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.52
    Confidence Interval (2-Sided) 95%
    0.64 to 3.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4256
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.44
    Confidence Interval (2-Sided) 95%
    0.59 to 3.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3790
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.35
    Confidence Interval (2-Sided) 95%
    0.69 to 2.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2554
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.47
    Confidence Interval (2-Sided) 95%
    0.76 to 2.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1961
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.53
    Confidence Interval (2-Sided) 95%
    0.80 to 2.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6916
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.15
    Confidence Interval (2-Sided) 95%
    0.58 to 2.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Number of Participants Who Maintained Clinical Response by Week 6
    Description The start of the 'maintained antidepressant response' was the time at which a participant demonstrates a 50% reduction from randomization in their HAM-D total score and where this response was maintained until the end of the treatment phase (week 6). Participants who met the 50% reduction at week 6 without having met it at week 4 were considered to have reached a maintained response, and therefore were censored at week 6. Where a participant met the criteria for maintained antidepressant response, the "time (in days) to maintained antidepressant response" was calculated as: (Date of assessment at which the maintained response commences minus Date of randomization) plus 1. Where a participant did not met the criteria for maintained antidepressant response, their time to response was censored at the last on-treatment assessment they undertake, up to and including the week 6 assessment.
    Time Frame Up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Number [Participants]
    14
    12.1%
    20
    17.4%
    19
    17%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.61
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.50 to 1.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.35
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.36 to 1.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in the Bech Melancholia Scale Total Score (Sum of Items 1, 2, 7, 8, 10, and 13 of the 17-item HAM-D Scale)
    Description The BECH scale was extracted from the HAMD-17 and comprised the 6 items (sum of items 1, 2, 7, 8, 10, and 13 of the 17-item HAM-D scale): Depressed Mood, Feelings of Guilt, Work and Activities, Retardation, Anxiety Psychic and Somatic Symptoms General. The BECH Total Score was calculated by summing the individual response scores. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. The lowest possible score was 0 (absence of depression) and the highest possible score was 22 (most severe measure of depression). Due to the small number of items , missing data was not imputed for the BECH Total Score. If any of the 6 items above were missing, the total score was not calculated at that visit. Value at randomization was the Baseline value. Change from Baseline in BECH Total Score was the difference between BECH Total Score at the time point being analyzed to randomization.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    -1.24
    (0.233)
    -1.94
    (0.237)
    -2.05
    (0.241)
    Week 2
    -2.17
    (0.287)
    -2.64
    (0.296)
    -2.79
    (0.307)
    Week 4
    -3.34
    (0.357)
    -4.01
    (0.368)
    -4.09
    (0.374)
    Week 6
    -3.69
    (0.394)
    -4.78
    (0.409)
    -4.21
    (0.421)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0362
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.69
    Confidence Interval (2-Sided) 95%
    -1.34 to -0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0155
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.81
    Confidence Interval (2-Sided) 95%
    -1.46 to -0.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2593
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.46
    Confidence Interval (2-Sided) 95%
    -1.27 to 0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1407
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.62
    Confidence Interval (2-Sided) 95%
    -1.44 to 0.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1933
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.67
    Confidence Interval (2-Sided) 95%
    -1.67 to 0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1500
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.74
    Confidence Interval (2-Sided) 95%
    -1.76 to 0.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0550
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.09
    Confidence Interval (2-Sided) 95%
    -2.21 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3627
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.52
    Confidence Interval (2-Sided) 95%
    -1.65 to 0.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR 16) Total Score
    Description QIDS-SR assessed symptoms severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criterion for major depressive disorder. It consisted of 16 separate items, defining 9 DSM-IV symptom criterion domains. A total score was obtained by summing scores on each domain. The lowest possible score was 0, which represented an absence of depression; the highest possible score was 27, which represented the most severe measure of depression. Due to the small number of items, missing data was not imputed for the QIDS-SR total score. If any of the 9 domains above were missing, the total score was not calculated at that visit. Value at randomization was the Baseline value. Change from Baseline in total score was the difference between QIDS total score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    -2.14
    (0.386)
    -3.17
    (0.395)
    -4.41
    (0.399)
    Week 2
    -3.64
    (0.445)
    -5.08
    (0.455)
    -5.48
    (0.473)
    Week 4
    -5.20
    (0.498)
    -6.78
    (0.510)
    -7.06
    (0.523)
    Week 6
    -6.17
    (0.543)
    -7.70
    (0.562)
    -7.58
    (0.588)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0616
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.03
    Confidence Interval (2-Sided) 95%
    -2.11 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -2.28
    Confidence Interval (2-Sided) 95%
    -3.36 to -1.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0239
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.44
    Confidence Interval (2-Sided) 95%
    -2.68 to -0.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0048
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.84
    Confidence Interval (2-Sided) 95%
    -3.12 to -0.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0270
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.58
    Confidence Interval (2-Sided) 95%
    -2.97 to -0.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0103
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.86
    Confidence Interval (2-Sided) 95%
    -3.27 to -0.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0497
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.53
    Confidence Interval (2-Sided) 95%
    -3.06 to -0.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0794
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.41
    Confidence Interval (2-Sided) 95%
    -2.98 to 0.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in the HAM-D Anxiety Factor Score (Sum of Items 10, 11, 12, 13, 15 and 17)
    Description The anxiety score was extracted from the HAM-D-17 and comprises of items 10, 11, 12, 13 and 15 from the HAM-D scale. The anxiety score was calculated by summing the individual response scores to these questions. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. The lowest possible score was 0 (absence of depression) and the highest possible score was 18 (most severe measure of depression). Due to the small number of items, missing data was not imputed for the anxiety score. If either of the anxiety items was missing, the total score was not calculated at that visit. Value at randomization was the Baseline value. Change from Baseline in anxiety score was the difference between the anxiety score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    -0.81
    (0.169)
    -1.09
    (0.172)
    -1.57
    (0.175)
    Week 2
    -1.40
    (0.185)
    -1.55
    (0.189)
    -1.73
    (0.197)
    Week 4
    -1.96
    (0.233)
    -2.31
    (0.239)
    -2.63
    (0.243)
    Week 6
    -2.37
    (0.235)
    -2.70
    (0.244)
    -2.56
    (0.254)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2400
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.28
    Confidence Interval (2-Sided) 95%
    -0.75 to 0.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0020
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.76
    Confidence Interval (2-Sided) 95%
    -1.23 to -0.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5605
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.15
    Confidence Interval (2-Sided) 95%
    -0.67 to 0.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2215
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.33
    Confidence Interval (2-Sided) 95%
    -0.86 to 0.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2870
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.35
    Confidence Interval (2-Sided) 95%
    -1.01 to 0.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0465
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.67
    Confidence Interval (2-Sided) 95%
    -1.33 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3399
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.32
    Confidence Interval (2-Sided) 95%
    -0.99 to 0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5931
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.18
    Confidence Interval (2-Sided) 95%
    -0.86 to 0.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percentage of Participants With Clinical Global Impression- Global Improvement (CGI-I) Score
    Description The CGI-I assessed scores range from 1 - Very much Improved to 7 - Very much worse, with 0 representing a participant that was not assessed. The assessed scores were dichotomized. Scores of 1 or 2 was in the first category, scoring 1. All other scores (except zero which was regarded as missing) was in the second category, scoring 0. The percentage of participants in the first category was calculated for each assessment.
    Time Frame Up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    4
    3.4%
    12
    10.4%
    9
    8%
    Week 2
    10
    8.6%
    25
    21.7%
    18
    16.1%
    Week 4
    33
    28.4%
    36
    31.3%
    39
    34.8%
    Week 6
    35
    30.2%
    44
    38.3%
    42
    37.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0562
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.83
    Confidence Interval (2-Sided) 95%
    0.97 to 8.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1596
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.22
    Confidence Interval (2-Sided) 95%
    0.73 to 6.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0067
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.91
    Confidence Interval (2-Sided) 95%
    1.34 to 6.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1154
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.93
    Confidence Interval (2-Sided) 95%
    0.85 to 4.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6895
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.13
    Confidence Interval (2-Sided) 95%
    0.62 to 2.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3654
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.32
    Confidence Interval (2-Sided) 95%
    0.72 to 2.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2408
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.44
    Confidence Interval (2-Sided) 95%
    0.78 to 2.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3066
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.39
    Confidence Interval (2-Sided) 95%
    0.74 to 2.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-S) Score
    Description The CGI-S assessed scores range from 1 - Very much Improved to 7 - Very much worse, with 0 representing a participant that was not assessed. For the CGI-S, remote, blinded MedAvante, raters assessed the participant's severity of illness considering their total clinical experience with the particular population being studied and information obtained during the Baseline HAMD interview with the participant. Value at randomization was the Baseline value. Change from Baseline in total score was the difference between CGI-S Score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    -0.42
    (0.075)
    -0.57
    (0.076)
    -0.69
    (0.077)
    Week 2
    -0.58
    (0.093)
    -0.83
    (0.095)
    -0.78
    (0.099)
    Week 4
    -0.98
    (0.111)
    -1.25
    (0.114)
    -1.26
    (0.116)
    Week 6
    -1.07
    (0.123)
    -1.45
    (0.127)
    -1.27
    (0.132)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1472
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.15
    Confidence Interval (2-Sided) 95%
    -0.36 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0107
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.27
    Confidence Interval (2-Sided) 95%
    -0.48 to -0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0603
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.25
    Confidence Interval (2-Sided) 95%
    -0.51 to 0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1458
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.20
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0941
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.27
    Confidence Interval (2-Sided) 95%
    -0.58 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0880
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.27
    Confidence Interval (2-Sided) 95%
    -0.59 to 0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments Placebo vs GW823296 60mg: Week 4
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0313
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.38
    Confidence Interval (2-Sided) 95%
    -0.73 to -0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2639
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.20
    Confidence Interval (2-Sided) 95%
    -0.55 to 0.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline in the Cognitive and Physical Function Questionnaire (CPFQ) Total Score
    Description CPFQ was a brief self-report scale which was designed to measure cognitive and executive dysfunction in mood and anxiety disorders. The CPFQ comprised of 7 questions assessing each of the most common complaints of depressed participants reporting fatigue or cognitive/executive problems. Each question was rated on a scale of 1 to 6, with 1 indicating greater than normal functioning, 2, indicating normal functioning, and with higher numbers indicating poorer functioning. Two versions of the CPFQ were utilized during the study. The Baseline CPFQ requested the participant reflect back over the past month. For the treatment period, the CPFQ requested the participant reflect back over the past week. Value at randomization was the Baseline value. Change from Baseline in Total Score was the difference between CPFQ Score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    -2.56
    (0.543)
    -4.13
    (0.551)
    -3.30
    (0.560)
    Week 2
    -3.43
    (0.588)
    -4.83
    (0.605)
    -5.37
    (0.625)
    Week 4
    -5.91
    (0.631)
    -6.68
    (0.652)
    -6.64
    (0.670)
    Week 6
    -6.34
    (0.688)
    -7.28
    (0.717)
    -7.53
    (0.746)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0421
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.57
    Confidence Interval (2-Sided) 95%
    -3.08 to -0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3394
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.74
    Confidence Interval (2-Sided) 95%
    -2.27 to 0.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0963
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.40
    Confidence Interval (2-Sided) 95%
    -3.05 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0235
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.94
    Confidence Interval (2-Sided) 95%
    -3.62 to -0.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3956
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.77
    Confidence Interval (2-Sided) 95%
    -2.54 to 1.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4273
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.73
    Confidence Interval (2-Sided) 95%
    -2.53 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3429
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.94
    Confidence Interval (2-Sided) 95%
    -2.89 to 1.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2403
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.19
    Confidence Interval (2-Sided) 95%
    -3.18 to 0.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Change From Baseline in Morning Sleep Questionnaire (MSQ) Total Sleep Time, Sleep Onset Latency and Wake Time After Sleep Onset
    Description The MSQ was a self-rated scale designed to assess effects on sleep and effects on next day functioning. The following variables were assessed in order to determine effects on sleep: total sleep time, sleep onset latency, number of nocturnal awakenings, wake time after sleep onset and sleep quality (from poor, assigned a score of 1, to excellent, assigned a score of 10). The refreshing value of the sleep was also determined (poor assigned a score of 1, to excellent, assigned a score of 10). Value at randomization was the Baseline value. Change from Baseline was calculated for each domain separately. Change from Baseline was the difference between score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1, total sleep time
    20.79
    (9.733)
    43.31
    (9.800)
    54.00
    (10.056)
    Week 2, total sleep time
    34.02
    (9.635)
    41.64
    (9.743)
    55.42
    (10.128)
    Week 4, total sleep time
    33.07
    (10.144)
    63.94
    (10.463)
    69.59
    (10.641)
    Week 6, total sleep time
    52.03
    (9.986)
    54.21
    (10.394)
    80.43
    (10.956)
    Week 1, sleep onset latency
    -12.50
    (6.310)
    -36.40
    (6.372)
    -37.99
    (6.547)
    Week 2, sleep onset latency
    -21.70
    (7.417)
    -34.15
    (7.508)
    -19.95
    (7.815)
    Week 4, sleep onset latency
    -27.84
    (6.940)
    -40.76
    (7.143)
    -38.39
    (7.290)
    Week 6, sleep onset latency
    -18.93
    (8.284)
    -47.51
    (8.684)
    -48.99
    (9.163)
    Week 1, wake time after sleep onset
    4.61
    (4.661)
    -12.58
    (4.807)
    -11.54
    (5.061)
    Week 2, wake time after sleep onset
    -8.10
    (5.652)
    -6.21
    (6.061)
    -2.83
    (6.298)
    Week 4, wake time after sleep onset
    -7.36
    (5.087)
    -9.86
    (5.505)
    -16.80
    (5.670)
    Week 6, wake time after sleep onset
    1.34
    (6.926)
    -13.17
    (7.479)
    -15.76
    (7.932)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1, total sleep time
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1030
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mixed effects repeated measures model
    Estimated Value 22.52
    Confidence Interval (2-Sided) 95%
    -4.58 to 49.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1, total sleep time
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0179
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 33.21
    Confidence Interval (2-Sided) 95%
    5.76 to 60.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2, total sleep time
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5773
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 7.62
    Confidence Interval (2-Sided) 95%
    -19.25 to 34.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2, total sleep time
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1250
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 21.40
    Confidence Interval (2-Sided) 95%
    -5.97 to 48.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4, total sleep time
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0344
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 30.87
    Confidence Interval (2-Sided) 95%
    2.29 to 59.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4, total sleep time
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0131
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 36.52
    Confidence Interval (2-Sided) 95%
    7.72 to 65.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6, total sleep time
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8794
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 2.18
    Confidence Interval (2-Sided) 95%
    -26.10 to 30.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6, total sleep time
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0556
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 28.40
    Confidence Interval (2-Sided) 95%
    -0.69 to 57.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1, sleep onset latency
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0078
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -23.90
    Confidence Interval (2-Sided) 95%
    -41.46 to -6.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1, sleep onset latency
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0052
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -25.49
    Confidence Interval (2-Sided) 95%
    -43.30 to -7.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2, sleep onset latency
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2373
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -12.45
    Confidence Interval (2-Sided) 95%
    -33.14 to 8.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2, sleep onset latency
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8707
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.75
    Confidence Interval (2-Sided) 95%
    -19.38 to 22.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo va GW823296 30 mg: Week 4, sleep onset latency
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1933
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -12.92
    Confidence Interval (2-Sided) 95%
    -32.43 to 6.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4, sleep onset latency
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2933
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -10.55
    Confidence Interval (2-Sided) 95%
    -30.26 to 9.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6, sleep onset latency
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0177
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -28.58
    Confidence Interval (2-Sided) 95%
    -52.15 to -5.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6, sleep onset latency
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0152
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -30.07
    Confidence Interval (2-Sided) 95%
    -54.29 to -5.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1, wake time after sleep onset
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0108
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -17.19
    Confidence Interval (2-Sided) 95%
    -30.36 to -4.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1, wake time after sleep onset
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0190
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -16.15
    Confidence Interval (2-Sided) 95%
    -29.61 to -2.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2, wake time after sleep onset
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8195
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.89
    Confidence Interval (2-Sided) 95%
    -14.43 to 18.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2, wake time after sleep onset
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5327
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 5.27
    Confidence Interval (2-Sided) 95%
    -11.35 to 21.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4, wake time after sleep onset
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7387
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -2.50
    Confidence Interval (2-Sided) 95%
    -17.24 to 12.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4, wake time after sleep onset
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2134
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -9.44
    Confidence Interval (2-Sided) 95%
    -24.35 to 5.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6, wake time after sleep onset
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1561
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -14.51
    Confidence Interval (2-Sided) 95%
    -34.61 to 5.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6, wake time after sleep onset
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1054
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -17.10
    Confidence Interval (2-Sided) 95%
    -37.84 to 3.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Change From Baseline in the MSQ Number of Nocturnal Awakenings
    Description The MSQ was a self-rated scale designed to assess effects on sleep and effects on next day functioning. The following variables were assessed in order to determine effects on sleep: total sleep time, sleep onset latency, number of nocturnal awakenings, wake time after sleep onset and sleep quality (from poor, assigned a score of 1, to excellent, assigned a score of 10). The refreshing value of the sleep was also determined (poor assigned a score of 1, to excellent, assigned a score of 10). Value at randomization was the Baseline value. Change from Baseline was calculated for each domain separately. Change from Baseline was the difference between score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.
    Time Frame Baseline and upto Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    -0.06
    (0.130)
    -0.63
    (0.134)
    -0.16
    (0.141)
    Week 2
    -0.52
    (0.116)
    -0.77
    (0.124)
    -0.47
    (0.130)
    Week 4
    -0.38
    (0.174)
    -0.43
    (0.187)
    -0.78
    (0.194)
    Week 6
    -0.63
    (0.152)
    -0.42
    (0.165)
    -0.87
    (0.175)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0024
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.57
    Confidence Interval (2-Sided) 95%
    -0.94 to -0.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6146
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.10
    Confidence Interval (2-Sided) 95%
    -0.47 to 0.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1442
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.25
    Confidence Interval (2-Sided) 95%
    -0.59 to 0.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8001
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.30 to 0.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8439
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.05
    Confidence Interval (2-Sided) 95%
    -0.55 to 0.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1259
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -0.91 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3709
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.20
    Confidence Interval (2-Sided) 95%
    -0.24 to 0.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments Placebo vs GW823296 60 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2993
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.24
    Confidence Interval (2-Sided) 95%
    -0.70 to 0.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Change From Baseline in the MSQ Sleep Quality and Refreshing Value of Sleep
    Description The MSQ was a self-rated scale designed to assess effects on sleep and effects on next day functioning. The following variables were assessed in order to determine effects on sleep: total sleep time, sleep onset latency, number of nocturnal awakenings, wake time after sleep onset and sleep quality (from poor, assigned a score of 1, to excellent, assigned a score of 10). The refreshing value of the sleep was also determined (poor assigned a score of 1, to excellent, assigned a score of 10). Value at randomization was the Baseline value. Change from Baseline was calculated for each domain separately. Change from Baseline was the difference between score at the time point being analyzed to randomization. If no post- randomization scores were available, change from Baseline was set to missing.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1, sleep quality
    0.73
    (0.196)
    1.32
    (0.198)
    1.45
    (0.203)
    Week 2, sleep quality
    1.03
    (0.204)
    1.46
    (0.206)
    1.54
    (0.214)
    Week 4, sleep quality
    1.39
    (0.212)
    2.12
    (0.219)
    1.82
    (0.222)
    Week 6, sleep quality
    1.77
    (0.234)
    2.34
    (0.243)
    2.09
    (0.254)
    Week 1, refreshing value of sleep
    0.97
    (0.193)
    1.31
    (0.195)
    1.60
    (0.200)
    Week 2, refreshing value of sleep
    1.15
    (0.201)
    1.48
    (0.203)
    1.80
    (0.211)
    Week 4, refreshing value of sleep
    1.61
    (0.216)
    2.30
    (0.223)
    2.00
    (0.227)
    Week 6, refreshing value of sleep
    1.86
    (0.242)
    2.23
    (0.252)
    2.57
    (0.264)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1, sleep quality
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0344
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.59
    Confidence Interval (2-Sided) 95%
    0.04 to 1.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1, sleep quality
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0111
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.72
    Confidence Interval (2-Sided) 95%
    0.17 to 1.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2, sleep quality
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1443
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.42
    Confidence Interval (2-Sided) 95%
    -0.15 to 0.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2, sleep quality
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0873
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.50
    Confidence Interval (2-Sided) 95%
    -0.07 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4, sleep quality
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0170
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.73
    Confidence Interval (2-Sided) 95%
    0.13 to 1.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4, sleep quality
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1675
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.42
    Confidence Interval (2-Sided) 95%
    -0.18 to 1.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6, sleep quality
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0956
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.56
    Confidence Interval (2-Sided) 95%
    -0.10 to 1.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6, sleep quality
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3503
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.32
    Confidence Interval (2-Sided) 95%
    -0.35 to 1.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1, refreshing value of sleep
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2147
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.34
    Confidence Interval (2-Sided) 95%
    -0.20 to 0.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1, refreshing value of sleep
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0233
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.63
    Confidence Interval (2-Sided) 95%
    0.09 to 1.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2, refreshing value of sleep
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2404
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.33
    Confidence Interval (2-Sided) 95%
    -0.22 to 0.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2, refreshing value of sleep
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0247
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.65
    Confidence Interval (2-Sided) 95%
    0.08 to 1.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4, refreshing value of sleep
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0271
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.08 to 1.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4, refreshing value of sleep
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2129
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.39
    Confidence Interval (2-Sided) 95%
    -0.22 to 1.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6, refreshing value of sleep
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2874
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.37
    Confidence Interval (2-Sided) 95%
    -0.31 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6, refreshing value of sleep
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0472
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.71
    Confidence Interval (2-Sided) 95%
    0.01 to 1.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Number of HAM-D Remitters
    Description A HAMD remitter was defined as a participant who had a HAMD Total Score <=7. The HAMD total score was calculated for each participant at each time point. Those participants with no missing value for HAMD total score were categorized as having a HAMD total score of <=7 or >7.
    Time Frame Up to Week 6

    Outcome Measure Data

    Analysis Population Description
    ITT Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 112 111
    Week 1
    2
    1.7%
    2
    1.7%
    1
    0.9%
    Week 2
    3
    2.6%
    3
    2.6%
    5
    4.5%
    Week 4
    6
    5.2%
    13
    11.3%
    14
    12.5%
    Week 6
    10
    8.6%
    19
    16.5%
    11
    9.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9824
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.13 to 7.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6227
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.54
    Confidence Interval (2-Sided) 95%
    0.05 to 6.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9967
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.20 to 5.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3550
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.00
    Confidence Interval (2-Sided) 95%
    0.46 to 8.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1009
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.35
    Confidence Interval (2-Sided) 95%
    0.85 to 6.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0455
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.80
    Confidence Interval (2-Sided) 95%
    1.02 to 7.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0507
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.30
    Confidence Interval (2-Sided) 95%
    1.00 to 5.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4962
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.38
    Confidence Interval (2-Sided) 95%
    0.55 to 3.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Number of Participants With Suicide-Related Events Based on the Columbia Suicidality Severity Rating Scale (CSSRS)
    Description Assessment of suicidality were done through use of the CSSRS for suicidal ideation and suicidal behavior. For suicidal ideation ratings were 1 to 5, where 1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation without intent to act, 4. Active suicidal ideation with any methods (not plan) without intent to act, 5. Active suicidal ideation with specific plan and intent and for suicidal behavior ratings were 6 to 12, Where 6. Actual attempt, 7. Engaged in non-suicidal self-injurious behavior, 8. Interrupted attempt, 9. Aborted attempt, 10. Preparatory acts or behavior, 11. Suicidal behavior, 12. Completed suicide. n= number participants with at least one CSSRS assessment after the first dose of study medication (i.e. on treatment or post treatment). Only those categories from CSSRS (1-12) are presented for which symptoms were actually observed in the participants. Categories with null values for all the arms have not been presented.
    Time Frame Up to 17 days post-treatment

    Outcome Measure Data

    Analysis Population Description
    The All Subjects Population was defined as all participants who received at least one dose of study medication. Only those participants with data available at the indicated time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 115 112 111
    Wish to be dead
    46
    39.7%
    41
    35.7%
    36
    32.1%
    Non-specific active suicidal thoughts
    12
    10.3%
    12
    10.4%
    11
    9.8%
    Active SI without intent to act (ITA)
    8
    6.9%
    9
    7.8%
    6
    5.4%
    Active SI with any methods (not plan) without ITA
    1
    0.9%
    2
    1.7%
    0
    0%
    Active SI with specific plan and intent
    0
    0%
    1
    0.9%
    0
    0%
    Engaged in non-suicidal self-injurious behavior
    1
    0.9%
    0
    0%
    0
    0%
    15. Secondary Outcome
    Title Number of Incidences of Discontinuation Emergent Signs and Symptoms Using the Discontinuation-Emergent Signs and Symptoms (DESS)
    Description The DESS scale consisted of 43 signs and symptoms, scored as 'new symptom', 'old symptom but worse', 'old symptom but improved' or 'symptom not present/old symptom but unchanged'. The total number of new signs and symptoms, old symptoms but worse, old symptoms but improved and the total number of new or old-but-worse signs and symptoms were calculated for each treatment and visit. n = number of subjects who had at least one of the 43 symptoms in the specified category. The summary for a specified category are of the number of symptoms the n subjects had in that category. Treatment period was up to Week 6.
    Time Frame Up to 17 days post-treatment

    Outcome Measure Data

    Analysis Population Description
    All subjects Population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 116 115 112
    New Symptom
    6.0
    (5.66)
    2.7
    (1.53)
    Old Symptom But Improved
    1.0
    (NA)
    5.0
    (5.66)
    3.0
    (1.41)
    Old Symptom But Worsened
    7.5
    (0.71)
    4.3
    (3.77)
    Unchanged/ Not present
    42.7
    (0.58)
    33.8
    (6.60)
    39.6
    (5.34)
    New or Old but Worsened
    9.0
    (7.55)
    5.0
    (4.30)
    16. Secondary Outcome
    Title Change From Baseline in the Massachusetts Sexual Function Questionnaire (MSFQ) Total Score in Males
    Description MSFQ included five items with a score ranging from 1 to 6 (1 = greater than normal; 2 = normal; 3 = minimally diminished; 5 = markedly diminished; and 6 = totally absent). The following areas of sexual functioning were included: diminished/absent libido; arousal difficulties; orgasm difficulties/anorgasmia; erectile dysfunction (males only) and degree of sexual satisfaction. A total score was used as a global measure of sexual dysfunction. The Baseline MSFQ requested the participant reflect back over the past month. For the treatment period, the follow-up MSFQ requested the participant reflect back over the past week. Change from Baseline was the value at post-Baseline visit minus Baseline value.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    All subjects Population (males). Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 48 40 39
    Week 1
    -1.88
    (0.690)
    -0.84
    (0.787)
    -2.43
    (0.795)
    Week 2
    -3.44
    (0.840)
    -1.00
    (0.968)
    -2.53
    (0.988)
    Week 4
    -3.88
    (1.003)
    -3.70
    (1.122)
    -4.59
    (1.141)
    Week 6
    -3.79
    (1.136)
    -4.47
    (1.269)
    -4.46
    (1.322)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3241
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.03
    Confidence Interval (2-Sided) 95%
    -1.03 to 3.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6020
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.56
    Confidence Interval (2-Sided) 95%
    -2.66 to 1.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0594
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 2.44
    Confidence Interval (2-Sided) 95%
    -0.10 to 4.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4828
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.92
    Confidence Interval (2-Sided) 95%
    -1.67 to 3.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9008
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.19
    Confidence Interval (2-Sided) 95%
    -2.80 to 3.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6428
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.71
    Confidence Interval (2-Sided) 95%
    -3.74 to 2.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6911
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.68
    Confidence Interval (2-Sided) 95%
    -4.06 to 2.70
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7026
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value -0.67
    Confidence Interval (2-Sided) 95%
    -4.14 to 2.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    17. Secondary Outcome
    Title Change From Baseline in the MSFQ Total Score in Females
    Description MSFQ included five items with a score ranging from 1 to 6 (1 = greater than normal; 2 = normal; 3 = minimally diminished; 5 = markedly diminished; and 6 = totally absent). The following areas of sexual functioning were included: diminished/absent libido; arousal difficulties; orgasm difficulties/anorgasmia; erectile dysfunction (males only) and degree of sexual satisfaction. A total score was used as a global measure of sexual dysfunction. The Baseline MSFQ requested the participant reflect back over the past month. For the treatment period, the follow-up MSFQ requested the participant reflect back over the past week. Change from Baseline was the value at post-Baseline visit minus Baseline value.
    Time Frame Baseline and up to Week 6

    Outcome Measure Data

    Analysis Population Description
    All Subject Population (female). Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    Measure Participants 68 75 73
    Week 1
    0.15
    (0.473)
    -0.82
    (0.473)
    0.62
    (0.467)
    Week 2
    -0.62
    (0.577)
    -1.38
    (0.578)
    0.32
    (0.578)
    Week 4
    -1.64
    (0.645)
    -2.62
    (0.653)
    -1.58
    (0.645)
    Week 6
    -2.39
    (0.699)
    -2.94
    (0.718)
    -1.68
    (0.724)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1301
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.97
    Confidence Interval (2-Sided) 95%
    -2.24 to 0.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 1
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4644
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.47
    Confidence Interval (2-Sided) 95%
    -0.79 to 1.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3382
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.76
    Confidence Interval (2-Sided) 95%
    -2.33 to 0.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2410
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.94
    Confidence Interval (2-Sided) 95%
    -0.63 to 2.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2768
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.98
    Confidence Interval (2-Sided) 95%
    -2.75 to 0.79
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 4
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9434
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.06
    Confidence Interval (2-Sided) 95%
    -1.70 to 1.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 30 mg
    Comments Placebo vs GW823296 30 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5796
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.55
    Confidence Interval (2-Sided) 95%
    -2.49 to 1.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, GW823296 60 mg
    Comments Placebo vs GW823296 60 mg: Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4753
    Comments
    Method Mixed Models Repeated Measures
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.71
    Confidence Interval (2-Sided) 95%
    -1.24 to 2.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame AEs were reported up to follow up (28 day) post-treatment (Week 6)
    Adverse Event Reporting Description AEs were reported for the All subjects Population which was defined as all participants who received at least one dose of study medication.
    Arm/Group Title Placebo GW823296 30 mg GW823296 60 mg
    Arm/Group Description Participants received one tablet of matching placebo, once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 30 milligrams (mg), once daily, in the evening for a period of 6 weeks. Participants received one tablet of GW823296 (orvepitant) 60 mg, once daily, in the evening for a period of 6 weeks.
    All Cause Mortality
    Placebo GW823296 30 mg GW823296 60 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/116 (0.9%) 0/115 (0%) 0/112 (0%)
    Serious Adverse Events
    Placebo GW823296 30 mg GW823296 60 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/116 (0.9%) 1/115 (0.9%) 3/112 (2.7%)
    Cardiac disorders
    Acute myocardial infarction 0/116 (0%) 1/115 (0.9%) 0/112 (0%)
    Injury, poisoning and procedural complications
    Road traffic accident 1/116 (0.9%) 0/115 (0%) 0/112 (0%)
    Nervous system disorders
    Convulsion 0/116 (0%) 0/115 (0%) 2/112 (1.8%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 0/116 (0%) 0/115 (0%) 1/112 (0.9%)
    Other (Not Including Serious) Adverse Events
    Placebo GW823296 30 mg GW823296 60 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 52/116 (44.8%) 61/115 (53%) 62/112 (55.4%)
    Gastrointestinal disorders
    Dry mouth 14/116 (12.1%) 11/115 (9.6%) 12/112 (10.7%)
    Nausea 16/116 (13.8%) 8/115 (7%) 10/112 (8.9%)
    Diarrhoea 8/116 (6.9%) 12/115 (10.4%) 10/112 (8.9%)
    Dyspepsia 5/116 (4.3%) 3/115 (2.6%) 6/112 (5.4%)
    Flatulence 6/116 (5.2%) 4/115 (3.5%) 4/112 (3.6%)
    Abdominal pain upper 2/116 (1.7%) 4/115 (3.5%) 7/112 (6.3%)
    General disorders
    Fatigue 2/116 (1.7%) 9/115 (7.8%) 7/112 (6.3%)
    Infections and infestations
    Upper respiratory tract infection 4/116 (3.4%) 7/115 (6.1%) 7/112 (6.3%)
    Nervous system disorders
    Headache 19/116 (16.4%) 19/115 (16.5%) 24/112 (21.4%)
    Somnolence 6/116 (5.2%) 12/115 (10.4%) 8/112 (7.1%)
    Dizziness 4/116 (3.4%) 9/115 (7.8%) 8/112 (7.1%)
    Psychiatric disorders
    Insomnia 2/116 (1.7%) 4/115 (3.5%) 9/112 (8%)
    Anxiety 2/116 (1.7%) 6/115 (5.2%) 5/112 (4.5%)

    Limitations/Caveats

    The study was terminated early upon the recommendation of an Independent Data Monitoring Committee. At the time the trial was terminated 343 participants had been randomized, compared to a target of 348 participants.

    More Information

    Certain Agreements

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

    GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

    Results Point of Contact

    Name/Title GSK Response Center
    Organization GlaxoSmithKline
    Phone 866-435-7343
    Email
    Responsible Party:
    GlaxoSmithKline
    ClinicalTrials.gov Identifier:
    NCT00880048
    Other Study ID Numbers:
    • 110833
    First Posted:
    Apr 13, 2009
    Last Update Posted:
    Oct 13, 2017
    Last Verified:
    Aug 1, 2017