A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose Study Evaluating the Efficacy and Safety of the Neurokinin-1 Receptor Antagonist Orvepitant (GW823296) in Post Traumatic Stress Disorder (PTSD)
Overview
- Phase
- Phase 2
- Intervention
- orvepitant
- Conditions
- Post-Traumatic Stress Disorder
- Sponsor
- GlaxoSmithKline
- Enrollment
- 132
- Locations
- 1
- Primary Endpoint
- Change From Baseline in the 17-item Clinician Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS) Total Severity Score at Week 12
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This is a 12-week, randomized, multicenter, double-blind, placebo controlled, fixed-dose parallel group study to assess the efficacy and safety of orvepitant (60 mg/day) versus placebo in subjects with a diagnosis of noncombat-related Posttraumatic Stress Disorder (PTSD), 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 randomized at the baseline visit to receive either orvepitant 60mg/day or placebo (1:1 ratio). Those subjects randomized to receive placebo will receive study medication identical in appearance to that received by subjects assigned to receive orvepitant.
Efficacy will be assessed using the Clinician Administered PTSD Scale (CAPS) as the primary efficacy measure. Key secondary efficacy endpoints will be based on the Davidson Trauma Scale (DTS), the Short PTSD Rating Interview (SPRINT), the Clinical Global Impression- Global Improvement and Severity of Illness Scales (CGI-I and CGI-S, respectively), the Hamilton Depression Rating Scale (HAM-D), the Cognitive and Physical Functioning Questionnaire (CPFQ) and the Pittsburgh Sleep Quality Index (PSQI).
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).
Detailed Description
The purpose of the current study is to test the safety and effects of orvepitant, an investigational drug for the treatment of noncombat-related PTSD. Efficacy will be assessed using standard symptom and severity rating scales (questionnaires). The Clinicain Adminstered PTSD Scale (CAPS) will serve as the primary measure of efficacy. Secondary efficacy endpoints include the CAPS subscale clusters (Re-Experiencing, Avoidance and Numbing, and Hyperarousal), the Davidson Trauma Scale (DTS), the Short PTSD Rating Interview (SPRINT), the Hamilton Depression Rating Scale (HAM-D), the Clinical Global Impression- Global Improvement and Severity of Illness Scale (CGI-I and CGI-S, respectively), the Cognitive and Physical Functioning Questionnaire (CPFQ) and the Pittsburgh Sleep Quality Index (PSQI). 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), Massachusetts Sexual Function Questionnaire (MSFQ), Discontinuation-Emergent Signs and Symptoms (DESS) scale 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 efficacy of orvepitant (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 CAPS 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. Upon completion of the screening period, eligible subjects will be randomly assigned at the baseline visit to one of two treatment regimens: orvepitant 60mg/day or placebo for a 12-week treatment phase. The chances of receiving each of the two 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, 6, 8, 10 and 12. 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. Women of child-bearing potential will also be required to attend the 28-Day follow-up visit for a pregnancy test. A further test will be performed 42 Days following the end of treatment. Male and female outpatients between the ages of 18 to 64 years inclusive with a primary diagnosis of noncombat-related PTSD will be enrolled into this study. A total of approximately 240 subjects are expected to be enrolled at approximately 25 different study sites in North America.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged 18-64 years, inclusive.
- •A primary diagnosis of noncombat-related Post traumatic Stress Disorder (PTSD)
- •Subjects with symptom severity considered to be at least moderate to severe.
Exclusion Criteria
- •Subjects whose symptoms are better accounted for by a diagnosis other than Post traumatic Stress Disorder (PTSD), subjects diagnosed with 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 who have a history of failing to respond to adequate treatment for PTSD with an antidepressant/anti-anxiety drug, i..e, failure to improve following administration of at least two other antidepressants/anti-anxiety drugs, each given for at least 4 weeks.
Arms & Interventions
Orvepitant 60 mg
60 mg/day
Intervention: orvepitant
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in the 17-item Clinician Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS) Total Severity Score at Week 12
Time Frame: Baseline (Day 1 pre-dose) and Week 12
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).
Secondary Outcomes
- 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(Baseline (Day 1 pre-dose) and up to Week 12)
- The Time to (Maintained) Clinical Response in Each Participants(Up to Week 12)
- Change From Baseline in the 17-item CAPS Total Severity Score at Weeks 1, 4, and 8(Baseline (Day 1 pre-dose) and Week 1, 4, 8)
- Percentage of Participants Remitting, Based on a CAPS Total Score < 20 at Weeks 1, 4, 8, and 12(Up to Week 12)
- Change From Baseline in the CAPS Re-experiencing Subscale Cluster Score at Weeks 1, 4, 8 and 12(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the CAPS Avoidance/Numbing (A/N) Subscale Cluster Score at Weeks 1, 4, 8, and 12(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the CAPS Hyperarousal Subscale Cluster Score at Weeks 1, 4, 8, and 12(Baseline (Day 1 pre-dose) and up to Week 12)
- Percentage of Participants Responding, Based on a Clinical Global Impression- Global Improvement (CGI-I) Score of 1 or 2, by Visit Week(Up to Week 12)
- Change From Baseline in the CGI-S Score, by Visit Week(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the Short PTSD Rating Review (SPRINT), by Visit Week(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the Cognitive and Physical Function Questionnaire (CPFQ) Total Score, by Visit Week(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the Self-rated Davidson Trauma Scale (DTS), by Visit Week(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the DTS Cluster Sub Score(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the Pittsburgh Sleep Quality Index (PSQI) Global Score, by Visit Week(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the PSQI Addendum for PTSD (PSQI-A) Global Score, by Visit Week(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in the CAPS Recurrent Distressing Dreams Item (B2) at Weeks 1, 4, 8, and 12(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in Hamilton Depression Rating Scale (HAM-D), by Visit Week(Baseline (Day 1 pre-dose) and up to Week 12)
- Number of Participant With Suicidal Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) During and Post Treatment(Baseline, Week 1, 2, 4, 6, 8, 10, 12 and Day 14 of follow-up (approximately 14 weeks))
- Number of Participant by Maximum Suicidal Ideation, Based on the C-SSRS During and Post Treatment(Baseline, Week 1, 2, 4, 6, 8, 10, 12 and Day 14 of follow-up (approximately 14 weeks))
- Change From Baseline in Massachusetts Sexual Function Questionnaire (MSFQ) Total Score and Erectile Dysfunction Score in Males(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in MSFQ Total Score in Females(Baseline (Day 1 pre-dose) and up to Week 12)
- Change From Baseline in MSFQ Items (Diminished/Absent Libido; Arousal Difficulties; Orgasm Difficulties/Anorgasmia and Degree of Sexual Satisfaction) Scores(Baseline (Day 1 pre-dose) and up to Week 12)