Orvepitant (GW823296) in Adult Post Traumatic Stress Disorder

NCT01000493 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 113211
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 26

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).

Conditions

Post-Traumatic Stress Disorder

Keywords

efficacy; double-blind; Clinician Administered PTSD Scale; placebo; Sleep; safety; CAPS; neurokinin-1 antagonist; orvepitant; PTSD; randomized; Post traumatic stress disorder; Phase II

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the 17-item Clinician Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS) Total Severity Score at 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).

  Baseline (Day 1 pre-dose) and Week 12

Secondary Outcomes (22)

• 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

Study Arms (2)

Orvepitant 60 mg

EXPERIMENTAL

60 mg/day

Drug: orvepitant

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

orvepitant DRUG

Neurokinin-1 (NK-1) antagonist

Also known as: GW823296

Orvepitant 60 mg

Placebo OTHER

Inactive placebo to match orvepitant 60 mg dosage form

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (26)

GSK Investigational Site

Birmingham, Alabama, 35216, United States

Location

GSK Investigational Site

Scottsdale, Arizona, 85251, United States

Location

GSK Investigational Site

Beverly Hills, California, 90210, United States

Location

GSK Investigational Site

Torrance, California, 90502, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32216, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Marietta, Georgia, 30060, United States

Location

GSK Investigational Site

Park Ridge, Illinois, 60068, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46260, United States

Location

GSK Investigational Site

Glen Burnie, Maryland, 21061, United States

Location

GSK Investigational Site

Weymouth, Massachusetts, 02190, United States

Location

GSK Investigational Site

Willingboro, New Jersey, 08046, United States

Location

GSK Investigational Site

The Bronx, New York, 10467, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27609, United States

Location

GSK Investigational Site

Dayton, Ohio, 45417, United States

Location

GSK Investigational Site

Garfield Heights, Ohio, 44125, United States

Location

GSK Investigational Site

Tulsa, Oklahoma, 74104, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29403, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38119, United States

Location

GSK Investigational Site

Austin, Texas, 78756, United States

Location

GSK Investigational Site

Dallas, Texas, 75231, United States

Location

GSK Investigational Site

Houston, Texas, 77008, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84132-2502, United States

Location

GSK Investigational Site

Seattle, Washington, 98104, United States

Location

GSK Investigational Site

Brown Deer, Wisconsin, 53223, United States

Location

GSK Investigational Site

Middleton, Wisconsin, 53562, United States

Location

Related Publications (1)

• Ratti E, Bettica P, Alexander R, Archer G, Carpenter D, Evoniuk G, Gomeni R, Lawson E, Lopez M, Millns H, Rabiner EA, Trist D, Trower M, Zamuner S, Krishnan R, Fava M. Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies. J Psychopharmacol. 2013 May;27(5):424-34. doi: 10.1177/0269881113480990. Epub 2013 Mar 28.

  PMID: 23539641 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

orvepitant

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Limitations and Caveats

The study was prematurely terminated on 11 May 2010 upon the recommendation of the Data Safety Monitoring Board.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2009
• First Posted: October 23, 2009
• Study Start: November 2, 2009
• Primary Completion: June 28, 2010
• Study Completion: June 28, 2010
• Last Updated: September 1, 2017
• Results First Posted: September 1, 2017

Record last verified: 2017-07

Locations

US (26)