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Orvepitant (GW823296) in Adult Post Traumatic Stress Disorder

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ClinicalTrials.gov Identifier: NCT01000493
Recruitment Status : Completed
First Posted : October 23, 2009
Results First Posted : September 1, 2017
Last Update Posted : September 1, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Post-Traumatic Stress Disorder
Interventions Drug: orvepitant
Other: Placebo
Enrollment 132
Recruitment Details A total of 129 participants with posttraumatic stress disorder were randomized to either orvepitant (GW823296) 60 milligrams (mg) or placebo at 26 centres in the United States. Intention to treat (ITT) population included total of 120 participants.
Pre-assignment Details The study was prematurely terminated on 11 May 2010 upon the recommendation of the Data Safety Monitoring Board.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks. Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Period Title: Overall Study
Started 60 69
Completed 21 14
Not Completed 39 55
Reason Not Completed
Adverse Event             3             6
Lack of Efficacy             1             1
Protocol Violation             1             8
Study closed/terminated             25             23
Lost to Follow-up             5             9
Physician Decision             1             1
Withdrawal by Subject             3             7
Arm/Group Title Placebo Orvepitant 60 mg Once Daily Total
Hide Arm/Group Description Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks. Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 60 69 129
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 60 participants 69 participants 129 participants
36.3  (10.88) 37.0  (12.24) 36.7  (11.59)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 69 participants 129 participants
Female
47
  78.3%
52
  75.4%
99
  76.7%
Male
13
  21.7%
17
  24.6%
30
  23.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 69 participants 129 participants
American Indian or Alaska Native
1
   1.7%
0
   0.0%
1
   0.8%
Asian
1
   1.7%
0
   0.0%
1
   0.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
17
  28.3%
20
  29.0%
37
  28.7%
White
38
  63.3%
48
  69.6%
86
  66.7%
More than one race
3
   5.0%
1
   1.4%
4
   3.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline in the 17-item Clinician Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS) Total Severity Score at Week 12
Hide Description The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, consisted 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. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 21 14
Least Squares Mean (Standard Error)
Unit of Measure: Score on scale
-25.75  (4.084) -31.38  (4.611)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3624
Comments The mixed effects model repeated measures (MMRM) analysis included treatment, week, Baseline total CAPS score and the treatment by week and Baseline. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.62
Confidence Interval (2-Sided) 95%
-17.9 to 6.65
Estimation Comments Comparison between Placebo and Orvepitant 60 mg at Week 12.
2.Secondary Outcome
Title Percentage of Participants Responding, Based on More Than Equal to (>=) 30 Percent (%) Reduction From Baseline in CAPS Total Severity Score at Weeks 1, 4, 8 and 12
Hide Description The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. Percentage of participants were calculated by total number of responders divided by number of participants assessed multiplied by 100.
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1 Number Analyzed 56 participants 62 participants
7 13
Week 4 Number Analyzed 42 participants 47 participants
50 38
Week 8 Number Analyzed 30 participants 25 participants
47 68
Week 12 Number Analyzed 21 participants 14 participants
52 79
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3156
Comments [Not Specified]
Method Logistic regression analysis
Comments The analysis method was logistic regression adjusted for Baseline CAPS total score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
0.54 to 6.76
Estimation Comments Comparison between Placebo and Orvepitant 60 mg at Week 1. Odds ratios represent the odds of improvement, relative to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3024
Comments [Not Specified]
Method Logistic regression analysis
Comments The analysis method was logistic regression adjusted for Baseline CAPS total score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.27 to 1.50
Estimation Comments Comparison between Placebo and Orvepitant 60 mg at Week 1. Odds ratios represent the odds of improvement, relative to placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1208
Comments [Not Specified]
Method Logistic regression analysis
Comments The analysis method was logistic regression adjusted for Baseline CAPS total score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.40
Confidence Interval (2-Sided) 95%
0.79 to 7.28
Estimation Comments Comparison between Placebo and Orvepitant 60 mg at Week 8. Odds ratios represent the odds of improvement, relative to placebo.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1331
Comments [Not Specified]
Method Logistic regression analysis
Comments The analysis method was logistic regression adjusted for Baseline CAPS total score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.27
Confidence Interval (2-Sided) 95%
0.70 to 15.4
Estimation Comments Comparison between Placebo and Orvepitant 60 mg at Week 1. Odds ratios represent the odds of improvement, relative to placebo.
3.Secondary Outcome
Title The Time to (Maintained) Clinical Response in Each Participants
Hide Description The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. The time required to maintain CAPS response has been summarized.
Time Frame Up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 10 9
Median (Inter-Quartile Range)
Unit of Measure: Days
35.5
(29.0 to 58.0)
30.0
(28.0 to 57.0)
4.Secondary Outcome
Title Change From Baseline in the 17-item CAPS Total Severity Score at Weeks 1, 4, and 8
Hide Description The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and Week 1, 4, 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 56 participants 62 participants
-9.24  (1.640) -10.11  (1.562)
Week 4 Number Analyzed 42 participants 47 participants
-24.24  (2.566) -21.43  (2.430)
Week 8 Number Analyzed 30 participants 25 participants
-23.33  (3.572) -27.97  (3.704)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7015
Comments The MMRM analysis model included treatment, week, Baseline total CAPS score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.87
Confidence Interval (2-Sided) 95%
-5.35 to 3.61
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4292
Comments The MMRM analysis model included treatment, week, Baseline total CAPS score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.81
Confidence Interval (2-Sided) 95%
-4.22 to 9.84
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 4.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3702
Comments The MMRM analysis model included treatment, week, Baseline total CAPS score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.64
Confidence Interval (2-Sided) 95%
-14.9 to 5.62
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 8.
5.Secondary Outcome
Title Percentage of Participants Remitting, Based on a CAPS Total Score < 20 at Weeks 1, 4, 8, and 12
Hide Description The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. Remitter defined as a participants who has a CAPS total score <20. Percentage of participants were calculated by total number of responders divided by number of participants assessed multiplied by 100.
Time Frame Up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed. The analysis method was logistic regression adjusted for Baseline CAPS total score. At a visit where there were no remitters, no analysis was performed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1 Number Analyzed 56 participants 62 participants
0 0
Week 4 Number Analyzed 42 participants 47 participants
5 2
Week 8 Number Analyzed 30 participants 25 participants
3 4
Week 12 Number Analyzed 21 participants 14 participants
10 7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5719
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.04 to 5.82
Estimation Comments Odds ratios represent the odds of improvement, relative to place. Comparison between placebo and orvepitant 60 mg once daily at Week 4.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9080
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.18
Confidence Interval 95%
0.07 to 20.1
Estimation Comments Odds ratios represent the odds of improvement, relative to place. Comparison between placebo and orvepitant 60 mg once daily at Week 8.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9486
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.07 to 12.5
Estimation Comments Odds ratios represent the odds of improvement, relative to place. Comparison between placebo and orvepitant 60 mg once daily at Week 12.
6.Secondary Outcome
Title Change From Baseline in the CAPS Re-experiencing Subscale Cluster Score at Weeks 1, 4, 8 and 12
Hide Description The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS assessed Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for PTSD, including criteria B-D (core symptom clusters of re-experiencing). The re-experiencing subscale cluster score was derived from the CAPS. The possible range was 5 to 25 with lower score indicates less severe symptoms and with a greater score indicating greater PTSD symptom severity. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 56 participants 62 participants
-3.1  (5.91) -4.6  (5.96)
Week 4 Number Analyzed 42 participants 47 participants
-8.4  (7.77) -8.0  (6.50)
Week 8 Number Analyzed 30 participants 25 participants
-8.5  (8.50) -10.0  (7.85)
Week 12 Number Analyzed 21 participants 14 participants
-10.0  (8.75) -12.9  (10.50)
7.Secondary Outcome
Title Change From Baseline in the CAPS Avoidance/Numbing (A/N) Subscale Cluster Score at Weeks 1, 4, 8, and 12
Hide Description The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS assessed DSM-IV diagnostic criteria for PTSD, including criteria B-D (core symptom clusters of A/N). The re-experiencing subscale cluster score was derived from the CAPS. The possible range is 7 to 35 with lower score indicates less severe symptoms and with a greater score indicating greater PTSD symptom severity. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 56 participants 62 participants
-3.22  (0.791) -2.55  (0.757)
Week 4 Number Analyzed 42 participants 47 participants
-8.99  (1.180) -8.48  (1.122)
Week 8 Number Analyzed 30 participants 25 participants
-7.74  (1.734) -9.96  (1.817)
Week 12 Number Analyzed 21 participants 14 participants
-9.13  (1.906) -11.11  (2.143)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5426
Comments The MMRM analysis model included treatment, week, Baseline CAPS A/N subscore and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
-1.51 to 2.85
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7552
Comments The MMRM analysis model included treatment, week, Baseline CAPS A/N subscore and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
-2.73 to 3.75
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 4.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3827
Comments The MMRM analysis model included treatment, week, Baseline CAPS A/N subscore and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.22
Confidence Interval (2-Sided) 95%
-7.27 to 2.83
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 8.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4915
Comments The MMRM analysis model included treatment, week, Baseline CAPS A/N subscore and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.98
Confidence Interval (2-Sided) 95%
-7.71 to 3.75
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 12.
8.Secondary Outcome
Title Change From Baseline in the CAPS Hyperarousal Subscale Cluster Score at Weeks 1, 4, 8, and 12
Hide Description The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS assessed DSM-IV diagnostic criteria for PTSD, including criteria B-D (core symptom clusters of hyperarousal). The re-experiencing subscale cluster score was derived from the CAPS. The possible range is 5 to 25 with lower score indicates less severe symptoms and with a greater score indicating greater PTSD symptom severity. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 56 participants 62 participants
-2.86  (0.672) -2.96  (0.639)
Week 4 Number Analyzed 42 participants 47 participants
-6.66  (0.982) -5.34  (0.930)
Week 8 Number Analyzed 30 participants 25 participants
-7.26  (1.324) -7.33  (1.394)
Week 12 Number Analyzed 21 participants 14 participants
-8.02  (1.388) -8.93  (1.689)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9190
Comments The MMRM analysis model included treatment, week, Baseline CAPS hyperarousal subscore and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-1.93 to 1.74
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3326
Comments The MMRM analysis model included treatment, week, Baseline CAPS hyperarousal subscore and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
-1.37 to 4.00
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 4.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9712
Comments The MMRM analysis model included treatment, week, Baseline CAPS hyperarousal subscore and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-3.91 to 3.77
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 8.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6711
Comments The MMRM analysis model included treatment, week, Baseline CAPS hyperarousal subscore and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.92
Confidence Interval (2-Sided) 95%
-5.22 to 3.39
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 12.
9.Secondary Outcome
Title Percentage of Participants Responding, Based on a Clinical Global Impression- Global Improvement (CGI-I) Score of 1 or 2, by Visit Week
Hide Description The global improvement items were rated on a 1-7 scale with 0 means not assessed (1: very much improved, 2: much improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: much worse, 7: very much worse). For the global improvement item, the clinician indicated their assessment of the participant’s total improvement or worsening compared with that individual's condition at the start of the study (the Baseline visit) whether or not the change was judged to be due to drug treatment. Responder was defined as a participant who had a CGI-I score of 1 or 2 (‘very much improved’ or ‘much improved’). It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. Percentage of participants were calculated by total number of responders divided by number of participants assessed multiplied by 100.
Time Frame Up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Measure Type: Number
Unit of Measure: Percentage of participants
Week 1 Number Analyzed 56 participants 62 participants
5 8
Week 2 Number Analyzed 53 participants 58 participants
15 21
Week 4 Number Analyzed 42 participants 47 participants
29 30
Week 6 Number Analyzed 37 participants 33 participants
35 58
Week 8 Number Analyzed 30 participants 25 participants
33 48
Week 10 Number Analyzed 27 participants 21 participants
30 57
Week 12 Number Analyzed 21 participants 14 participants
43 71
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5532
Comments The analysis method was logistic regression adjusted for Baseline total Clinical Global Impression-Severity of Illness scales (CGI-S) score.
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.57
Confidence Interval (2-Sided) 95%
0.36 to 6.92
Estimation Comments Odds ratios represent the odds of improvement, relative to placebo. Comparison between placebo and orvepitant 60 mg once daily at Week 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4508
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
0.54 to 3.93
Estimation Comments Odds ratios represent the odds of improvement, relative to placebo. The analysis method was logistic regression adjusted for Baseline total CGI-S score. Comparison between placebo and orvepitant 60 mg once daily at Week 2.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9234
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.42 to 2.62
Estimation Comments Odds ratios represent the odds of improvement, relative to placebo. The analysis method was logistic regression adjusted for Baseline total CGI-S score. Comparison between placebo and orvepitant 60 mg once daily at Week 4.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0662
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
0.94 to 6.53
Estimation Comments Odds ratios represent the odds of improvement, relative to placebo. The analysis method was logistic regression adjusted for Baseline total CGI-S score. Comparison between placebo and orvepitant 60 mg once daily at Week 1
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2767
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
0.61 to 5.48
Estimation Comments Odds ratios represent the odds of improvement, relative to placebo. The analysis method was logistic regression adjusted for Baseline total CGI-S score. Comparison between placebo and orvepitant 60 mg once daily at Week 8.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0588
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.17
Confidence Interval (2-Sided) 95%
0.96 to 10.5
Estimation Comments Odds ratios represent the odds of improvement, relative to placebo. The analysis method was logistic regression adjusted for Baseline total CGI-S score. Comparison between placebo and orvepitant 60 mg once daily at Week 10.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1032
Comments [Not Specified]
Method Logistic regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.33
Confidence Interval (2-Sided) 95%
0.78 to 14.1
Estimation Comments Odds ratios represent the odds of improvement, relative to placebo. The analysis method was logistic regression adjusted for Baseline total CGI-S score. Comparison between placebo and orvepitant 60 mg once daily at Week 12.
10.Secondary Outcome
Title Change From Baseline in the CGI-S Score, by Visit Week
Hide Description The severity of illness items were rated on a 1-7 scale with 0 means not assessed (1: normal, not at all ill, 2: borderline mentally ill, 3: mildly ill, 4: moderately ill, 5: markedly ill, 6: severely ill, 7: among the most extremely ill participants). For the severity of illness item, the clinician indicated his/her assessment of the participant severity of illness considering their total clinical experience with the particular population being studied. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 56 participants 62 participants
-0.23  (0.064) -0.35  (0.061)
Week 2 Number Analyzed 53 participants 58 participants
-0.44  (0.093) -0.65  (0.089)
Week 4 Number Analyzed 42 participants 47 participants
-0.84  (0.127) -0.84  (0.120)
Week 6 Number Analyzed 37 participants 33 participants
-0.73  (0.140) -1.03  (0.140)
Week 8 Number Analyzed 30 participants 25 participants
-0.67  (0.150) -1.28  (0.155)
Week 10 Number Analyzed 27 participants 21 participants
-0.83  (0.188) -1.26  (0.195)
Week 12 Number Analyzed 21 participants 14 participants
-1.10  (0.195) -1.42  (0.216)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1743
Comments The MMRM analysis model included treatment, week, baseline CGI-S score, and the treatment by week and baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.29 to 0.05
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1181
Comments The MMRM analysis model included treatment, week, baseline CGI-S score, and the treatment by week and baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.46 to 0.05
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 2.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9698
Comments The MMRM analysis model included treatment, week, baseline CGI-S score, and the treatment by week and baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.35 to 0.34
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 4.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1341
Comments The MMRM analysis model included treatment, week, baseline CGI-S score, and the treatment by week and baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.69 to 0.09
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 6.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0064
Comments The MMRM analysis model included treatment, week, baseline CGI-S score, and the treatment by week and baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.61
Confidence Interval (2-Sided) 95%
-1.04 to -0.18
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 8.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1095
Comments The MMRM analysis model included treatment, week, baseline CGI-S score, and the treatment by week and baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-0.98 to 0.10
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 10.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2814
Comments The MMRM analysis model included treatment, week, baseline CGI-S score, and the treatment by week and baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.90 to 0.27
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 12.
11.Secondary Outcome
Title Change From Baseline in the Short PTSD Rating Review (SPRINT), by Visit Week
Hide Description The SPRINT consists of 8 items that assess the core symptoms of PTSD, as well as related aspects of somatic malaise, stress vulnerability and functional impairment. Each item was rated on a 5 point scale (0: not at all, 1: a little bit, 2: moderately, 3: quiet a lot and 4: very much), total score 0-32; with higher scores means more severity. Also, it provided the information about how the participant feeling (as a percentage) and symptoms improved since beginning of treatment (rated on a 5 point scale [0: worse, 1: a no change, 2: minimally, 3: much and 4: very much]). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 56 participants 62 participants
-2.1  (4.30) -2.1  (4.69)
Week 2 Number Analyzed 53 participants 58 participants
-3.1  (5.44) -5.1  (5.63)
Week 4 Number Analyzed 42 participants 47 participants
-4.5  (6.24) -4.9  (6.68)
Week 6 Number Analyzed 37 participants 33 participants
-4.6  (5.85) -7.5  (7.24)
Week 8 Number Analyzed 30 participants 25 participants
-6.0  (5.89) -8.2  (6.56)
Week 10 Number Analyzed 27 participants 21 participants
-6.0  (6.80) -8.1  (7.34)
Week 12 Number Analyzed 21 participants 14 participants
-7.8  (6.66) -8.8  (7.23)
12.Secondary Outcome
Title Change From Baseline in the Self-rated Davidson Trauma Scale (DTS), by Visit Week
Hide Description This instrument consists of 17 items which parallel the DSM criteria for PTSD. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) rated using 5-point scale. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The DTS cluster includes intrusion (items 1-4, 17 [score 0-40]), avoidance/numbing (A/N; items 5-11 [score 0-56]) and hyperarousal (items 12-16 [score 0-40]). The total score (0-136) was added, lower score indicates less symptoms and higher scores means more severity, <20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 55 participants 61 participants
-11.3  (19.00) -17.7  (20.60)
Week 2 Number Analyzed 52 participants 57 participants
-18.3  (22.64) -25.4  (24.00)
Week 4 Number Analyzed 41 participants 46 participants
-24.7  (27.76) -26.5  (24.36)
Week 6 Number Analyzed 36 participants 32 participants
-21.3  (29.04) -36.1  (22.27)
Week 8 Number Analyzed 30 participants 25 participants
-27.8  (27.58) -42.9  (24.41)
Week 10 Number Analyzed 27 participants 21 participants
-25.3  (26.46) -40.4  (32.88)
Week 12 Number Analyzed 21 participants 14 participants
-33.3  (29.97) -51.9  (25.73)
13.Secondary Outcome
Title Change From Baseline in the DTS Cluster Sub Score
Hide Description This instrument consists of 17 items which parallel the DSM criteria for PTSD. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem; 4: extreme, incapacitating) rated using 5-point scale and added to get total score. There were 8 items including guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment. The DTS cluster includes intrusion (items 1-4, 17 [score 0-40]), A/N (items 5-11 [score 0-56]) and hyperarousal (items 12-16 [score 0-40]) with lower score indicates less symptoms and higher scores means more severity, <20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and >80: extreme PTSD symptoms. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Intrusion, Week 1 Number Analyzed 55 participants 61 participants
-4.7  (7.98) -5.8  (7.56)
Intrusion, Week 2 Number Analyzed 52 participants 57 participants
-5.6  (8.10) -7.9  (7.57)
Intrusion, Week 4 Number Analyzed 41 participants 46 participants
-8.4  (9.33) -8.7  (8.25)
Intrusion, Week 6 Number Analyzed 36 participants 32 participants
-6.1  (8.76) -10.0  (7.92)
Intrusion, Week 8 Number Analyzed 30 participants 25 participants
-8.3  (8.84) -12.5  (8.62)
Intrusion, Week 10 Number Analyzed 27 participants 21 participants
-7.0  (7.75) -12.5  (12.02)
Intrusion, Week 12 Number Analyzed 21 participants 14 participants
-10.0  (8.23) -15.7  (10.93)
A/N, Week 1 Number Analyzed 55 participants 61 participants
-2.8  (8.91) -5.2  (10.00)
A/N, Week 2 Number Analyzed 52 participants 57 participants
-6.7  (10.91) -8.7  (11.76)
A/N, Week 4 Number Analyzed 41 participants 46 participants
-8.6  (15.06) -9.1  (11.82)
A/N, Week 6 Number Analyzed 36 participants 32 participants
-7.8  (15.62) -13.0  (10.96)
A/N, Week 8 Number Analyzed 30 participants 25 participants
-11.0  (13.22) -16.2  (11.87)
A/N, Week 10 Number Analyzed 27 participants 21 participants
-10.1  (12.77) -14.6  (13.88)
A/N, Week 12 Number Analyzed 21 participants 14 participants
-13.2  (15.59) -19.9  (9.89)
Hyperarousal, Week 1 Number Analyzed 55 participants 61 participants
-3.8  (7.39) -6.8  (7.41)
Hyperarousal, Week 2 Number Analyzed 52 participants 57 participants
-5.9  (8.41) -8.7  (8.09)
Hyperarousal, Week 4 Number Analyzed 41 participants 46 participants
-7.6  (8.49) -8.7  (8.67)
Hyperarousal, Week 6 Number Analyzed 36 participants 32 participants
-7.4  (8.08) -13.0  (8.11)
Hyperarousal, Week 8 Number Analyzed 30 participants 25 participants
-8.5  (9.67) -14.2  (7.54)
Hyperarousal, Week 10 Number Analyzed 27 participants 21 participants
-8.2  (9.41) -13.3  (9.93)
Hyperarousal, Week 12 Number Analyzed 21 participants 14 participants
-10.1  (9.31) -16.3  (9.46)
14.Secondary Outcome
Title Change From Baseline in the Pittsburgh Sleep Quality Index (PSQI) Global Score, by Visit Week
Hide Description The PSQI was a self-rated questionnaire to assess sleep quality and disturbances. Individual items (19) generate 7-component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction. The global score generated by addition of individual score excluding use of sleeping medication component. It contains 15 objective (about frequency of sleep disturbances and subjective sleep quality) and 4 subjective (typical bedtime, wake-up time, sleep latency and sleep duration) items with score range from 0: no to 3: severe difficulty. The PSQI Global Score ranges from 0 to 21 and a global score > 5 was suggestive of significant sleep disturbance. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 53 participants 58 participants
-1.6  (3.81) -3.2  (4.11)
Week 2 Number Analyzed 50 participants 56 participants
-2.0  (3.71) -4.3  (4.50)
Week 4 Number Analyzed 37 participants 42 participants
-3.2  (4.60) -3.5  (4.72)
Week 6 Number Analyzed 34 participants 32 participants
-3.5  (4.02) -4.3  (4.71)
Week 8 Number Analyzed 27 participants 23 participants
-3.2  (4.57) -5.2  (4.69)
Week 10 Number Analyzed 26 participants 20 participants
-3.5  (5.11) -4.6  (4.35)
Week 12 Number Analyzed 20 participants 14 participants
-4.6  (5.34) -4.1  (5.21)
15.Secondary Outcome
Title Change From Baseline in the PSQI Addendum for PTSD (PSQI-A) Global Score, by Visit Week
Hide Description The PSQI-A was self-report instrument to assess disruptive nocturnal behavior (DNB) in PTSD participants with 7 types of DNB. These items include frequency of 1: hot flashes, 2: general nervousness, 3: memories or nightmares of traumatic experience, 4: severe anxiety or panic, not related to traumatic memories, 5: bad dreams, not related to traumatic memories, 6: episodes of terror or screaming during sleep without fully awakening and 7: episodes of acting out dreams, such as kicking, punching, running, or screaming. Each item was rated on a scale (0: not in the past month, 1: less than once a week, 2: once or twice a week and 3: three or more times a week) with global score range of 0-21. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 1 participants 0 participants
-1.0 [1]   (NA)
Week 2 Number Analyzed 5 participants 2 participants
-2.6  (2.07) 0.5  (7.78)
Week 4 Number Analyzed 41 participants 46 participants
-1.9  (3.57) -2.8  (3.58)
Week 6 Number Analyzed 5 participants 5 participants
0.0  (2.55) -7.0  (6.75)
Week 8 Number Analyzed 30 participants 25 participants
-2.2  (3.99) -4.0  (4.85)
Week 10 Number Analyzed 4 participants 6 participants
1.5  (3.32) -1.7  (6.35)
Week 12 Number Analyzed 21 participants 14 participants
-3.3  (4.27) -3.6  (4.83)
[1]
SD was not derived as one participant was present at this time point.
16.Secondary Outcome
Title Change From Baseline in the CAPS Recurrent Distressing Dreams Item (B2) at Weeks 1, 4, 8, and 12
Hide Description The B2 asked participant about ‘Have you ever had unpleasant dreams about the event(s)? How often in the past month?’ Both frequency (0: never; 4: daily or all the time) and ‘at their worst, how much distress or discomfort did these dreams cause you? Did these dreams wake you up? [If yes, ask:] What were you feeling or doing when you awoke? How long does it usually take to get back to sleep? [Listen for report of panic symptoms, yelling, posturing] intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The total score 0-8, higher scores means more severity. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 56 participants 62 participants
-1.2  (2.47) -1.0  (2.48)
Week 4 Number Analyzed 42 participants 47 participants
-1.4  (2.72) -1.7  (2.48)
Week 8 Number Analyzed 30 participants 25 participants
-1.9  (2.65) -2.3  (3.12)
Week 12 Number Analyzed 21 participants 14 participants
-1.4  (3.25) -2.4  (3.10)
17.Secondary Outcome
Title Change From Baseline in Hamilton Depression Rating Scale (HAM-D), by Visit Week
Hide Description The HAM-D was observer-rated depressive symptom rating scale to measure the severity of depressive symptoms in participants with primary depressive illness. The items were ranked on a scale of 0-4 (0: absent; 4: greatest severity) or 0-2 (0: no difficulty; 2: difficulty falling asleep). In addition to the total score (0-66; with higher score indicates more depression), the HAM-D anxiety factor score (sum of items 10, 11, 12, 13, 15 and 17) and the melancholia subscore (sum of items 1, 2, 7, 8, 10, and 13) of the 17-item HAM-D scale was analyzed. The melancholia subscale was derived from three formal psychometric criteria (calibration, ascending monotonicity and dispersion). It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 56 participants 62 participants
-1.72  (0.518) -3.64  (0.491)
Week 2 Number Analyzed 53 participants 58 participants
-3.42  (0.645) -5.36  (0.613)
Week 4 Number Analyzed 42 participants 47 participants
-3.57  (0.866) -5.46  (0.819)
Week 6 Number Analyzed 37 participants 33 participants
-3.73  (0.865) -6.62  (0.865)
Week 8 Number Analyzed 30 participants 25 participants
-3.83  (1.030) -6.69  (1.061)
Week 10 Number Analyzed 27 participants 21 participants
-4.53  (1.143) -7.41  (1.215)
Week 12 Number Analyzed 21 participants 14 participants
-6.21  (1.341) -6.48  (1.507)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments The MMRM analysis model included treatment, week, Baseline total HAM-D score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.92
Confidence Interval (2-Sided) 95%
-3.33 to -0.50
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 1
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0311
Comments The MMRM analysis model included treatment, week, Baseline total HAM-D score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.94
Confidence Interval (2-Sided) 95%
-3.71 to -0.18
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 2.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1155
Comments The MMRM analysis model included treatment, week, Baseline total HAM-D score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.89
Confidence Interval (2-Sided) 95%
-4.26 to 0.47
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 4.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0210
Comments The MMRM analysis model included treatment, week, Baseline total HAM-D score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.89
Confidence Interval (2-Sided) 95%
-5.33 to -0.45
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 6.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0582
Comments The MMRM analysis model included treatment, week, Baseline total HAM-D score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.86
Confidence Interval (2-Sided) 95%
-5.83 to 0.10
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 8.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0927
Comments The MMRM analysis model included treatment, week, Baseline total HAM-D score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.88
Confidence Interval (2-Sided) 95%
-6.25 to 0.49
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 10.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Orvepitant 60 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8954
Comments The MMRM analysis model included treatment, week, Baseline total HAM-D score, and the treatment by week and Baseline by week interaction terms. Week was used as the repeated effect in the model.
Method MMRM analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-4.36 to 3.83
Estimation Comments Comparison between placebo and orvepitant 60 mg once daily at Week 12.
18.Secondary Outcome
Title Change From Baseline in the Cognitive and Physical Function Questionnaire (CPFQ) Total Score, by Visit Week
Hide Description The Massachusetts CPFQ was a brief self-report scale to measure cognitive and executive dysfunction in mood and anxiety disorders. The CPFQ comprises 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: greater than normal, 2: normal, 3: minimally diminished, 4: moderately diminished, 5: markedly diminished and 6: totally absent functioning with total score 7-42; higher score indicating more dysfunction. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 56 64
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Number Analyzed 1 participants 0 participants
5.0 [1]   (NA)
Week 2 Number Analyzed 5 participants 2 participants
-1.6  (4.72) -2.5  (2.12)
Week 4 Number Analyzed 41 participants 46 participants
-2.0  (4.77) -2.2  (7.29)
Week 6 Number Analyzed 5 participants 5 participants
-0.8  (5.26) -5.2  (6.30)
Week 8 Number Analyzed 30 participants 25 participants
-3.9  (5.11) -4.0  (7.38)
Week 10 Number Analyzed 4 participants 6 participants
1.0  (4.55) -0.8  (14.33)
Week 12 Number Analyzed 21 participants 14 participants
-5.3  (5.52) -4.2  (6.76)
[1]
SD was not derived as one participant was present at this time point.
19.Secondary Outcome
Title Change From Baseline in Massachusetts Sexual Function Questionnaire (MSFQ) Total Score and Erectile Dysfunction Score in Males
Hide Description The MSFQ was derived from the Guided Interview Questionnaire for males and from the Arizona Sexual Experience Scale. The questionnaire includes five items with a score ranging from 1-6 (1: greater than normal; 2: normal; 3: minimally diminished; 4: moderately diminished; 5: markedly diminished and 6: totally absent with total score 5-30; higher score indicating more dysfunction). The areas of sexual functioning included were total score and erectile dysfunction (males only). A total score was used as a global measure of sexual dysfunction. A follow-up version of the questionnaire includes an additional sixth item of the participant’s global impression of improvement, with a score ranging from 1 to 6. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Male participants from all subject population used. All subject population defined as participants who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 13 17
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Total score, Week 1 Number Analyzed 1 participants 0 participants
-1.0 [1]   (NA)
Total score, Week 2 Number Analyzed 3 participants 0 participants
-2.3  (6.03)
Total score, Week 4 Number Analyzed 8 participants 11 participants
0.1  (2.03) -0.6  (5.48)
Total score, Week 6 Number Analyzed 1 participants 3 participants
7.0 [1]   (NA) 1.0  (1.73)
Total score, Week 8 Number Analyzed 5 participants 9 participants
-1.2  (2.77) -3.7  (5.59)
Total score, Week 10 Number Analyzed 1 participants 3 participants
-1.0 [1]   (NA) -7.3  (6.11)
Total score, Week 12 Number Analyzed 3 participants 6 participants
2.0  (9.17) -3.2  (6.62)
Erectile dysfunction score, Week 1 Number Analyzed 1 participants 0 participants
0.0 [1]   (NA)
Erectile dysfunction score, Week 2 Number Analyzed 3 participants 0 participants
-0.3  (0.58)
Erectile dysfunction score, Week 4 Number Analyzed 8 participants 11 participants
0.1  (0.64) -0.3  (1.56)
Erectile dysfunction score, Week 6 Number Analyzed 1 participants 3 participants
1.0 [1]   (NA) -0.3  (0.58)
Erectile dysfunction score, Week 8 Number Analyzed 5 participants 9 participants
-0.2  (0.45) -0.7  (1.12)
Erectile dysfunction score, Week 10 Number Analyzed 1 participants 3 participants
-1.0 [1]   (NA) -1.3  (1.53)
Erectile dysfunction score, Week 12 Number Analyzed 3 participants 6 participants
0.3  (1.53) -0.8  (1.33)
[1]
SD was not derived as one participant was present at this time point.
20.Secondary Outcome
Title Change From Baseline in MSFQ Total Score in Females
Hide Description The MSFQ was derived from the Guided Interview Questionnaire for males and from the Arizona Sexual Experience Scale. The questionnaire includes five items with a score ranging from 1-6 (1: greater than normal; 2: normal; 3: minimally diminished; 4: moderately diminished; 5: markedly diminished and 6: totally absent with total score 5-30; higher score indicating more dysfunction). The areas of sexual functioning included were total score used as a global measure of sexual dysfunction. A follow-up version of the questionnaire includes an additional sixth item of the participant’s global impression of improvement, with a score ranging from 1 to 6. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Female participants from all subject population used. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 47 52
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Total score, Week 1 Number Analyzed 3 participants 2 participants
-0.3  (0.58) 0.5  (4.95)
Total score, Week 2 Number Analyzed 3 participants 5 participants
1.0  (3.61) 0.2  (4.32)
Total score, Week 4 Number Analyzed 34 participants 37 participants
-1.1  (4.42) -1.4  (5.23)
Total score, Week 6 Number Analyzed 6 participants 4 participants
-1.3  (7.23) 0.5  (3.79)
Total score, Week 8 Number Analyzed 25 participants 18 participants
-1.4  (4.90) -2.1  (4.66)
Total score, Week 10 Number Analyzed 5 participants 5 participants
-1.0  (2.24) -2.4  (2.61)
Total score, Week 12 Number Analyzed 18 participants 9 participants
-2.9  (5.84) -1.0  (4.30)
21.Secondary Outcome
Title Change From Baseline in MSFQ Items (Diminished/Absent Libido; Arousal Difficulties; Orgasm Difficulties/Anorgasmia and Degree of Sexual Satisfaction) Scores
Hide Description The MSFQ was derived from the Guided Interview Questionnaire for males and from the Arizona Sexual Experience Scale. The questionnaire includes five items with a score ranging from 1-6 (1: greater than normal; 2: normal; 3: minimally diminished; 4: moderately diminished; 5: markedly diminished and 6: totally absent). The areas of sexual functioning included were diminished/absent libido; arousal difficulties; orgasm difficulties/anorgasmia and degree of sexual satisfaction. A follow-up version of the questionnaire includes an additional sixth item of the participant’s global impression of improvement, with a score ranging from 1 to 6. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).
Time Frame Baseline (Day 1 pre-dose) and up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 60 69
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Absent libido score, Week 1 Number Analyzed 4 participants 2 participants
-0.3  (0.50) 1.0  (1.41)
Absent libido score, Week 2 Number Analyzed 6 participants 5 participants
0.2  (0.75) -0.2  (1.48)
Absent libido score, Week 4 Number Analyzed 42 participants 48 participants
-0.3  (1.15) -0.2  (1.65)
Absent libido score, Week 6 Number Analyzed 7 participants 7 participants
-0.3  (1.98) 0.6  (1.51)
Absent libido score, Week 8 Number Analyzed 30 participants 27 participants
-0.4  (1.38) -0.6  (1.28)
Absent libido score, Week 10 Number Analyzed 6 participants 8 participants
0.2  (0.41) -0.6  (0.74)
Absent libido score, Week 12 Number Analyzed 21 participants 15 participants
-0.6  (1.77) -0.4  (1.06)
Arousal difficulties score, Week 1 Number Analyzed 4 participants 2 participants
0.0  (0.00) 0.0  (0.00)
Arousal difficulties score, Week 2 Number Analyzed 6 participants 5 participants
0.3  (0.52) 0.4  (0.89)
Arousal difficulties score, Week 4 Number Analyzed 42 participants 48 participants
-0.3  (1.18) -0.3  (1.14)
Arousal difficulties score, Week 6 Number Analyzed 7 participants 7 participants
0.0  (1.83) 0.3  (0.49)
Arousal difficulties score, Week 8 Number Analyzed 30 participants 27 participants
-0.4  (1.33) -0.6  (1.22)
Arousal difficulties score, Week 10 Number Analyzed 6 participants 8 participants
0.0  (0.00) -0.8  (1.04)
Arousal difficulties score, Week 12 Number Analyzed 21 participants 15 participants
-0.6  (1.53) -0.3  (1.39)
Anorgasmia score, Week 1 Number Analyzed 4 participants 2 participants
0.0  (0.00) -0.5  (2.12)
Anorgasmia score, Week 2 Number Analyzed 6 participants 5 participants
-0.7  (2.42) -0.4  (1.52)
Anorgasmia score, Week 4 Number Analyzed 42 participants 48 participants
-0.2  (1.01) -0.2  (1.38)
Anorgasmia score, Week 6 Number Analyzed 7 participants 7 participants
0.0  (1.53) 0.3  (1.38)
Anorgasmia score, Week 8 Number Analyzed 30 participants 27 participants
-0.2  (1.13) -0.6  (1.31)
Anorgasmia score, Week 10 Number Analyzed 6 participants 8 participants
-0.5  (1.22) -1.1  (1.36)
Anorgasmia score, Week 12 Number Analyzed 21 participants 15 participants
-0.4  (1.63) -0.4  (1.18)
Sexual satisfaction score, Week 1 Number Analyzed 4 participants 2 participants
-0.3  (0.50) 0.0  (1.41)
Sexual satisfaction score, Week 2 Number Analyzed 6 participants 5 participants
-0.3  (1.51) 0.4  (0.89)
Sexual satisfaction score, Week 4 Number Analyzed 42 participants 48 participants
-0.1  (1.22) -0.5  (1.47)
Sexual satisfaction score, Week 6 Number Analyzed 7 participants 7 participants
0.0  (3.00) -0.3  (0.49)
Sexual satisfaction score, Week 8 Number Analyzed 30 participants 27 participants
-0.4  (1.10) -0.6  (1.45)
Sexual satisfaction score, Week 10 Number Analyzed 6 participants 8 participants
-0.5  (0.84) -1.3  (1.16)
Sexual satisfaction score, Week 12 Number Analyzed 21 participants 15 participants
-0.6  (1.63) -0.5  (1.30)
22.Secondary Outcome
Title Number of Participant With Suicidal Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) During and Post Treatment
Hide Description The C-SSRS used to assess severity and change of suicidality by integrating both behavior and ideation and to be completed by the participants. The SSRS track change in the severity/density of suicidality. The interview was initiated with 5 (yes/no) questions; rated on 1-5 point scale, presented in ascending order of severity, about suicidal ideation. If the answers to the first 2 ideation questions were “yes,” the clinician asked questions 3-5. If the answers to ideation questions 1 and 2 were “no,” then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt and preparatory acts or behaviors. Participants analyzed were number of participants with at least one C-SSRS assessment after the first dose of study medication (that is on treatment or post treatment).
Time Frame Baseline, Week 1, 2, 4, 6, 8, 10, 12 and Day 14 of follow-up (approximately 14 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All subject population. Only those participants available at the time of indicated time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 59 68
Measure Type: Number
Unit of Measure: Participants
Actual attempt 1 1
Engaged in non-suicidal self-injurious behavior 1 1
Interrupted attempt 2 1
Aborted attempt 1 1
Preparatory acts or behaviors 0 1
23.Secondary Outcome
Title Number of Participant by Maximum Suicidal Ideation, Based on the C-SSRS During and Post Treatment
Hide Description The C-SSRS used to assess severity and change of suicidality by integrating both behavior and ideation and to be completed by the participants. The SSRS track change in the severity/density of suicidality. It assessed intensity of ideation (a potentially important marker of severity), specifically asking about frequency, duration, intrusiveness, controllability, and deterrents. The interview was initiated with 5 (yes/no) questions; rated on 1-5 point scale, presented in ascending order of severity, about suicidal ideation. The clinician asked 5 questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation without intent to act, active suicidal ideation with any methods (not plan) without intent to act and active suicidal ideation with specific plan and intent. Participants analyzed were number of participants with at least one C-SSRS assessment after the first dose of study medication (that is on treatment or post treatment).
Time Frame Baseline, Week 1, 2, 4, 6, 8, 10, 12 and Day 14 of follow-up (approximately 14 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All subject population. Only those participants available at the time of indicated time points were analyzed.
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description:
Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks.
Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
Overall Number of Participants Analyzed 59 68
Measure Type: Number
Unit of Measure: Participants
Wish to be dead 9 9
Non-specific active suicidal thoughts 2 4
Active suicidal ideation without intent to act 1 0
Active suicidal ideation with any methods 1 0
Active suicidal ideation with plan and intent 1 0
Time Frame AE and SAE were reported from the start of investigational product and until the follow-up contact (up to 18 weeks).
Adverse Event Reporting Description All subject population was used for the analysis of safety (AE and SAE).
 
Arm/Group Title Placebo Orvepitant 60 mg Once Daily
Hide Arm/Group Description Participants assigned to take one tablet of matching placebo of orvepitant each day in the evening (once daily) up to 12 weeks. Participants assigned to take one tablet of orvepitant 60 mg each day in the evening (once daily) up to 12 weeks.
All-Cause Mortality
Placebo Orvepitant 60 mg Once Daily
Affected / at Risk (%) Affected / at Risk (%)
Total   0/60 (0.00%)      0/69 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Orvepitant 60 mg Once Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/60 (1.67%)      1/69 (1.45%)    
Nervous system disorders     
Convulsion  1  0/60 (0.00%)  1/69 (1.45%) 
Psychiatric disorders     
Depression  1  1/60 (1.67%)  0/69 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Orvepitant 60 mg Once Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/60 (45.00%)      34/69 (49.28%)    
Gastrointestinal disorders     
Nausea  1  6/60 (10.00%)  7 7/69 (10.14%)  8
Diarrhoea  1  5/60 (8.33%)  5 4/69 (5.80%)  4
Dry mouth  1  3/60 (5.00%)  3 5/69 (7.25%)  6
Dyspepsia  1  2/60 (3.33%)  2 6/69 (8.70%)  6
General disorders     
Fatigue  1  3/60 (5.00%)  4 3/69 (4.35%)  3
Infections and infestations     
Upper respiratory tract infection  1  6/60 (10.00%)  6 4/69 (5.80%)  4
Nasopharyngitis  1  5/60 (8.33%)  6 3/69 (4.35%)  3
Musculoskeletal and connective tissue disorders     
Back pain  1  0/60 (0.00%)  0 4/69 (5.80%)  5
Nervous system disorders     
Headache  1  8/60 (13.33%)  8 11/69 (15.94%)  13
Somnolence  1  3/60 (5.00%)  3 9/69 (13.04%)  10
Paraesthesia  1  4/60 (6.67%)  4 1/69 (1.45%)  1
Psychiatric disorders     
Insomnia  1  3/60 (5.00%)  3 2/69 (2.90%)  2
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
The study was prematurely terminated on 11 May 2010 upon the recommendation of the Data Safety Monitoring Board.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01000493     History of Changes
Other Study ID Numbers: 113211
First Submitted: October 15, 2009
First Posted: October 23, 2009
Results First Submitted: March 31, 2017
Results First Posted: September 1, 2017
Last Update Posted: September 1, 2017