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Ganaxolone in Posttraumatic Stress Disorder (PTSD)

Primary Purpose

PTSD

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ganaxolone
Placebo
Sponsored by
Marinus Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PTSD focused on measuring PTSD, Posttraumatic Stress Disorder, pharmacotherapy, ganaxolone

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • VA San Diego Healthcare System/ University of California, San Diego
  • Washington DC VA Medical Center/ Uniformed Services University of the Health Services
  • VA Boston Healthcare Services/ Spaulding Rehabilitation Hospital
  • Manchester VA Medical Center/ Dartmouth College
  • Durham VA Medical Center /Duke University Medical Center
  • Cincinnati VA Medical Center/ University of Cincinnati
  • Charleston VA Medica Center/ Medical University of South Carolina
  • White River Junction VA Medical Center/ Dartmouth College

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ganaxolone

Placebo

Arm Description

active

non-active

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Full Information

First Posted
April 19, 2011
Last Updated
November 30, 2022
Sponsor
Marinus Pharmaceuticals
Collaborators
INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium, U.S. Army Medical Research and Development Command
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1. Study Identification

Unique Protocol Identification Number
NCT01339689
Brief Title
Ganaxolone in Posttraumatic Stress Disorder (PTSD)
Official Title
A Proof-of-Concept, Double-blind, Randomized, Placebo-controlled Study of Ganaxolone in Posttraumatic Stress Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
April 2011 (Actual)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Marinus Pharmaceuticals
Collaborators
INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium, U.S. Army Medical Research and Development Command

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PTSD
Keywords
PTSD, Posttraumatic Stress Disorder, pharmacotherapy, ganaxolone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ganaxolone
Arm Type
Experimental
Arm Description
active
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
non-active
Intervention Type
Drug
Intervention Name(s)
Ganaxolone
Other Intervention Name(s)
GNX
Intervention Description
200-600 mg bid, capsules, up to 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
PBO
Intervention Description
capsules, bid, up to 12 weeks
Primary Outcome Measure Information:
Title
Change From Baseline in Clinician-Administered Posttrautamtic Stress Disorder (PTSD) Scale (CAPS) to Week 6
Description
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.
Time Frame
Baseline (Week 0) and at Week 2, Week 4 and Week 6
Secondary Outcome Measure Information:
Title
Change From Baseline in PTSD Re-Experience Score
Description
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.
Time Frame
Baseline (Week 0) and at Week 2, Week 4 and Week 6
Title
Change From Baseline in PTSD Avoidance Score
Description
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.
Time Frame
Baseline (Week 0) and at Week 2, Week 4 and Week 6
Title
Change From Baseline in PTSD Hyperarousal Score
Description
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.
Time Frame
Baseline (Week 0) and at Week 2, Week 4 and Week 6
Title
Number of Participants With Response to Clinical Global Impression - Improvement (Investigator) (CGI-II) Scale
Description
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.
Time Frame
Week 2, Week 4 and Week 6
Title
Number of Participants With Response to CGI-I Subject Scale Clinical Global Impression - Improvement (Subject) (CGI-IS) Scale
Description
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.
Time Frame
Week 2, Week 4 and Week 6
Title
Change From Baseline in PTSD Checklist (PCL) Scores
Description
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.
Time Frame
Baseline (Week 0) and at Week 2, Week 4 and Week 6
Title
Change From Baseline in Profile of Mood States (POMS) Total Score
Description
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.
Time Frame
Baseline (Week 0) and Week 6
Title
Change From Baseline in Patient Health Questionnaire (PHQ-9) Score
Description
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.
Time Frame
Baseline (Week 0) and Week 6
Title
Change From Baseline in Insomnia Severity Index (ISI) Score
Description
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.
Time Frame
Baseline (Week 0) and Week 6
Title
Change From Baseline in Connor-Davidson Resilience Scale (CD-RISC) Score
Description
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
Time Frame
Baseline (Week 0) and Week 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christine E Marx, MD, MA
Organizational Affiliation
Duke University Medical Center and Durham VA Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ann Rasmusson, MD
Organizational Affiliation
Boston University School of Medicine Research Affiliate, National Center for PTSD
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA San Diego Healthcare System/ University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Washington DC VA Medical Center/ Uniformed Services University of the Health Services
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
VA Boston Healthcare Services/ Spaulding Rehabilitation Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02130
Country
United States
Facility Name
Manchester VA Medical Center/ Dartmouth College
City
Manchester
State/Province
New Hampshire
ZIP/Postal Code
03104
Country
United States
Facility Name
Durham VA Medical Center /Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Cincinnati VA Medical Center/ University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States
Facility Name
Charleston VA Medica Center/ Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
White River Junction VA Medical Center/ Dartmouth College
City
White River Junction
State/Province
Vermont
ZIP/Postal Code
05009
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28667510
Citation
Rasmusson AM, Marx CE, Jain S, Farfel GM, Tsai J, Sun X, Geracioti TD, Hamner MB, Lohr J, Rosse R, Summerall L, Naylor JC, Cusin C, Lang AJ, Raman R, Stein MB. A randomized controlled trial of ganaxolone in posttraumatic stress disorder. Psychopharmacology (Berl). 2017 Aug;234(15):2245-2257. doi: 10.1007/s00213-017-4649-y. Epub 2017 Jul 1.
Results Reference
derived

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Ganaxolone in Posttraumatic Stress Disorder (PTSD)

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