PTSDPhase 2NCT01339689
Ganaxolone in Posttraumatic Stress Disorder (PTSD)
A Phase 2 study testing Ganaxolone in people with PTSD, run by Marinus Pharmaceuticals at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- PTSD
- What is being tested?
- Ganaxolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 8 sitesUnited States
- Study dates
- Apr 2011to Mar 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
VA Boston Healthcare Services/ Spaulding Rehabilitation Hospital
Boston, Massachusetts, 02130
Charleston VA Medica Center/ Medical University of South Carolina
Charleston, South Carolina, 29401
Cincinnati VA Medical Center/ University of Cincinnati
Cincinnati, Ohio, 45220
Durham VA Medical Center /Duke University Medical Center
Durham, North Carolina, 27705
Manchester VA Medical Center/ Dartmouth College
Manchester, New Hampshire, 03104
VA San Diego Healthcare System/ University of California, San Diego
San Diego, California, 92093
Washington DC VA Medical Center/ Uniformed Services University of the Health Services
Washington D.C., District of Columbia, 20422
White River Junction VA Medical Center/ Dartmouth College
White River Junction, Vermont, 05009
About this study
Official title: A Proof-of-Concept, Double-blind, Randomized, Placebo-controlled Study of Ganaxolone in Posttraumatic Stress Disorder
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.
- Conditions
- PTSD
- Being tested
- Ganaxolone, Placebo
- Keywords
- PTSD, Posttraumatic Stress Disorder, pharmacotherapy, ganaxolone
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GanaxoloneDrug
Also called GNX
200-600 mg bid, capsules, up to 12 weeks
PlaceboDrug
Also called PBO
capsules, bid, up to 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ganaxolone | Experimental | active Receives: Drug: Ganaxolone |
| Placebo | Placebo comparator | non-active Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Week 0) and at Week 2, Week 4 and Week 6
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Baseline (Week 0) and Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2011 (estimated)
- Study startApr 2011
- Primary completionJan 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marinus Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium, U.S. Army Medical Research and Development Command
- Responsible party
- Sponsor
- Investigators
- Christine E Marx, MD, MA, Principal investigator, Duke University Medical Center and Durham VA Medical CenterAnn Rasmusson, MD, Principal investigator, Boston University School of Medicine Research Affiliate, National Center for PTSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01339689
- Sponsor's protocol ID
- 1042-0700
- Status last verified
- Nov 2022
- First submitted
- 19 Apr 2011
- Last updated
- 29 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 28667510
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of-Concept, Double-blind, Randomized, Placebo-controlled Study of Ganaxolone in Posttraumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT01339689
- Acronym / sponsor ID
- 1042-0700
- Conditions
- PTSD
- Keywords
- PTSD, Posttraumatic Stress Disorder, pharmacotherapy, ganaxolone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Marinus PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium, U.S. Army Medical Research and Development Command
- Study start
- Apr 2011 (actual)
- Primary completion
- Jan 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 21 Apr 2011 (estimated)
- Results
- Posted 29 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ganaxolone | Experimental | Drug: Ganaxoloneactive |
| Placebo | Placebo comparator | Drug: Placebonon-active |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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 (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GanaxoloneAlso: GNX200-600 mg bid, capsules, up to 12 weeks | Drug | Ganaxolone |
| PlaceboAlso: PBOcapsules, bid, up to 12 weeks | Drug | Placebo |
Primary outcome
Change From Baseline in Clinician-Administered Posttrautamtic Stress Disorder (PTSD) Scale (CAPS) to Week 6
Time frame: Baseline (Week 0) and at Week 2, Week 4 and 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.
10 secondary outcomes
Change From Baseline in PTSD Re-Experience Score
Time frame: Baseline (Week 0) and at Week 2, Week 4 and Week 6
Change From Baseline in PTSD Avoidance Score
Time frame: Baseline (Week 0) and at Week 2, Week 4 and Week 6
Change From Baseline in PTSD Hyperarousal Score
Time frame: 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
Time frame: 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
Time frame: Week 2, Week 4 and Week 6
Change From Baseline in PTSD Checklist (PCL) Scores
Time frame: Baseline (Week 0) and at Week 2, Week 4 and Week 6
Change From Baseline in Profile of Mood States (POMS) Total Score
Time frame: Baseline (Week 0) and Week 6
Change From Baseline in Patient Health Questionnaire (PHQ-9) Score
Time frame: Baseline (Week 0) and Week 6
Change From Baseline in Insomnia Severity Index (ISI) Score
Time frame: Baseline (Week 0) and Week 6
Change From Baseline in Connor-Davidson Resilience Scale (CD-RISC) Score
Time frame: Baseline (Week 0) and Week 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28667510Rasmusson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine E Marx, MD, MA principal investigator
Duke University Medical Center and Durham VA Medical Center
Ann Rasmusson, MD principal investigator
Boston University School of Medicine Research Affiliate, National Center for PTSD
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ganaxolone in people with PTSD, run by Marinus Pharmaceuticals at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Clinician-Administered Posttrautamtic Stress Disorder (PTSD) Scale (CAPS) to Week 6 (time frame: Baseline (Week 0) and at Week 2, Week 4 and Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01339689, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2022.