Orvepitant (GW823296) in Adult Post Traumatic Stress Disorder

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01000493
First received: October 15, 2009
Last updated: February 23, 2012
Last verified: March 2011
  Purpose

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).


Condition Intervention Phase
Posttraumatic Stress Disorder (PTSD)
Post-Traumatic Stress Disorder
Drug: orvepitant
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in the 17-item Clinician Administered PTSD (CAPS) total severity score. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of subjects responding based on reducation in CAPS total severity score. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of subjects remitting based on reducation in CAPS total score. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Columbia Suicidality Severity Rating Scale [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Massachusetts Sexual Function Questionnaire (MSFQ) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 240
Study Start Date: November 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Orvepitant 60 mg
60 mg/day
Drug: orvepitant
Neurokinin-1 (NK-1) antagonist
Other Name: GW823296
Placebo Comparator: Placebo Other: Placebo
Inactive placebo to match orvepitant 60 mg dosage form

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01000493

  Show 26 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01000493     History of Changes
Other Study ID Numbers: 113211
Study First Received: October 15, 2009
Last Updated: February 23, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
efficacy
double-blind
Clinician Administered PTSD Scale
placebo
Sleep
safety
CAPS
neurokinin-1 antagonist
orvepitant
PTSD
randomized
Post traumatic stress disorder
Phase II

Additional relevant MeSH terms:
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders
Neurokinin A
Substance P
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014