Ganaxolone in Posttraumatic Stress Disorder (PTSD)

Study Overview
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Brief Summary
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This Phase 2 proof-of-concept study is a double-blind, randomized, placebo-controlled, 15-week investigation of ganaxolone versus placebo for the treatment of Posttraumatic Stress Disorder (PTSD). Up to 120 participants will be enrolled and randomized to receive either ganaxolone or placebo for 6 weeks. After 6 weeks of randomized treatment all participants will continue for 6 weeks on ganaxolone. The aim of the study is to assess the efficacy of ganaxolone compared to placebo for the treatment of PTSD symptoms after 6 weeks of treatment using the Clinician-Administered PTSD Rating Scale (CAPS). The second aim of the study is to evaluate the safety and tolerability of ganaxolone in the PTSD population.

Official Title
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A Proof-of-Concept, Double-blind, Randomized, Placebo-controlled Study of Ganaxolone in Posttraumatic Stress Disorder

Conditions
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PTSD

Intervention / Treatment
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* Drug: Ganaxolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Veteran or civilian adult outpatients 18-55 years of age, with primary PTSD as defined by Diagnostic and Statistical manual of Mental Disorders-IV (DSM-IV) for at least 6 months Must be in general good health-confirmed by medical history, physical examination, and screening laboratory results Negative urine drug screen for drugs of abuse Negative urine pregnancy test for females of childbearing potential Sexually active participants are required to use a medically acceptable form of birth control Key Exclusion Criteria Clinically unstable medical disease; progressive CNS disorder/disease; history of seizures (except childhood febrile seizure); moderate or severe traumatic brain injury (TBI) Females who are pregnant or currently breast feeding Current or past psychotic disorder, bipolar Type I disorder, or dementia Participants with recent drug abuse or dependency (excluding nicotine and caffeine) Participants unwilling to comply with the required alcohol prohibition during the trial Current suicidal or homicidal ideation necessitating intervention, and those with a history of suicide attempt in the past 10 years Participants with pending litigation related to the traumatic event Participants who are unwilling to withhold grapefruit or grapefruit juice for the duration of the study Participants receiving psychotherapy without a stable paradigm for at least 3 months Non-English speaking participants.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ganaxolone<br>active | Drug: Ganaxolone<br>* 200-600 mg bid, capsules, up to 12 weeks<br>* Other names: GNX;|
| Placebo Comparator: Placebo<br>non-active | Drug: Placebo<br>* capsules, bid, up to 12 weeks<br>* Other names: PBO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinician-Administered Posttrautamtic Stress Disorder (PTSD) Scale (CAPS) to Week 6 | The CAPS was a structured interview that queries participants about each of the 17 Diagnostic and Statistical manual of Mental Disorders IV (DSM-IV) criteria B, C, and D symptoms of PTSD. Each item has a frequency score (0-4) and intensity score (0-4). The CAPS total score is the sum of frequency and intensity ratings for each item and the score range was 0: no symptoms to 136: severe symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Week 0) and at Week 2, Week 4 and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in PTSD Re-Experience Score | The CAPS was a structured interview that queries participants about each of the 17 Diagnostic and Statistical manual of Mental Disorders IV (DSM-IV) criteria B, C, and D symptoms of PTSD. Each item has a frequency score (0-4) and intensity score (0-4). The Re-experience score is the sum of frequency and intensity ratings for items from cluster B and the score range was 0: no symptoms to 40: severe symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Week 0) and at Week 2, Week 4 and Week 6 | 
| Change From Baseline in PTSD Avoidance Score | The CAPS was a structured interview that queries participants about each of the 17 Diagnostic and Statistical manual of Mental Disorders IV (DSM-IV) criteria B, C, and D symptoms of PTSD. Each item has a frequency score (0-4) and intensity score (0-4). The Avoidance score is the sum of frequency and intensity ratings for items from cluster C.and the score range was 0: no symptoms to 56: severe symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Week 0) and at Week 2, Week 4 and Week 6 | 
| Change From Baseline in PTSD Hyperarousal Score | The CAPS was a structured interview that queries participants about each of the 17 Diagnostic and Statistical manual of Mental Disorders IV (DSM-IV) criteria B, C, and D symptoms of PTSD. Each item has a frequency score (0-4) and intensity score (0-4). The Hyperarousal score is the sum of frequency and intensity ratings for items from cluster D and the score range was 0: no symptoms to 40: severe symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Week 0) and at Week 2, Week 4 and Week 6 | 
| Number of Participants With Response to Clinical Global Impression - Improvement (Investigator) (CGI-II) Scale | The CGI-II scale is a 7-point scale where the investigator was required to assess how much the participant's illness has improved or worsened relative to a Baseline state at the beginning of the intervention, and rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Higher score indicated worse symptoms. The score was grouped into two categories for analysis: Responders=1 or 2, Non-responders=3-7. | Week 2, Week 4 and Week 6 | 
| Number of Participants With Response to CGI-I Subject Scale Clinical Global Impression - Improvement (Subject) (CGI-IS) Scale | The CGI-IS scale is a 7-point scale where the participant assesses how much the illness has improved or worsened relative to a Baseline state at the beginning of the intervention, and rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Higher score indicated worse symptoms. The score was grouped into two categories for analysis: Responders=1 or 2, Non-responders=3-7. | Week 2, Week 4 and Week 6 | 
| Change From Baseline in PTSD Checklist (PCL) Scores | The PCL is a 17-item self-report scale representing all DSM-IV criteria for PTSD, including re-experiencing, avoidance and numbing, and hyperarousal criteria. Each item is scored 1-5 (1=not at all; 2=a little bit; 3=moderately; 4=quite a bit; 5=extremely). The total score is the sum of 17 item scores and ranged from 17: no symptoms to 85: severe symptoms. Higher score indicated worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Week 0) and at Week 2, Week 4 and Week 6 | 
| Change From Baseline in Profile of Mood States (POMS) Total Score | The POMS is a factor-analytically derived 65 item self-report inventory with 5-point measures of five dimensions of negative mood: anger/irritability, anxiety/tension, depression/dejection, confusion/bewilderment, and fatigue/inertia, as well as vigor/activity. Total score was calculated as Fatigue + Mood (sum [Confusion, anger, Anxiety/Tension, Depression])- Vigor. Score ranged from 0: no symptoms to 200: severe symptoms; higher score indicated worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Week 0) and Week 6 | 
| Change From Baseline in Patient Health Questionnaire (PHQ-9) Score | The PHQ-9 is the nine-item depression scale of the Patient Health Questionnaire. The nine items of the PHQ-9 are based directly on the nine diagnostic criteria for major depressive disorder in the DSM-IV. Each item is scored 0-3 (0=not at all; 1=several days; 2=more than half the days; 3= nearly every day). The total score is the sum of 9 item scores and ranged 0: no depression to 27: severe depression. The higher the total score, the worse the depression. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Week 0) and Week 6 | 
| Change From Baseline in Insomnia Severity Index (ISI) Score | The ISI is a self-rated questionnaire assessing the difficulty over the past two weeks with falling to sleep, awakening in the middle of the night, and early morning awakening, as well as the degree to which insomnia impairs daily function. It included 5 items (rst item has 3 sub-questions), so a total of 7 questions. Each question is scored 0-4 (0=none, 1=mild, 2=moderate, 3=severe, 4=very severe). The total score is the sum of 7 item scores and ranged from 0: no symptoms to 28: severe symptoms. Higher score indicated worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Week 0) and Week 6 | 
| Change From Baseline in Connor-Davidson Resilience Scale (CD-RISC) Score | The CD-RISC comprises 25 items, each rated on a 5-point scale (0-4), with higher scores reflecting greater resilience that may be a target for treatment in stress disorders. The total score is the sum of 25 item scores and ranged from 0: no symptoms to 100: worse symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value | Baseline (Week 0) and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ganaxolone, PTSD, Posttraumatic Stress Disorder, pharmacotherapy