Orvepitant (GW823296) in Adult Post Traumatic Stress Disorder

NCT ID: NCT01000493

Last Updated: 2017-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-02
• Study Completion Date: 2010-06-28

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).

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.

Conditions

Post-Traumatic Stress Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Orvepitant 60 mg

60 mg/day

Group Type: EXPERIMENTAL

orvepitant

Intervention Type: DRUG

Neurokinin-1 (NK-1) antagonist

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Inactive placebo to match orvepitant 60 mg dosage form

Interventions

orvepitant

Neurokinin-1 (NK-1) antagonist

Intervention Type: DRUG

Placebo

Inactive placebo to match orvepitant 60 mg dosage form

Intervention Type: OTHER

Other Intervention Names

GW823296

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Birmingham, Alabama, United States

GSK Investigational Site

Scottsdale, Arizona, United States

GSK Investigational Site

Beverly Hills, California, United States

GSK Investigational Site

Torrance, California, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Marietta, Georgia, United States

GSK Investigational Site

Park Ridge, Illinois, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Glen Burnie, Maryland, United States

GSK Investigational Site

Weymouth, Massachusetts, United States

GSK Investigational Site

Willingboro, New Jersey, United States

GSK Investigational Site

The Bronx, New York, United States

GSK Investigational Site

Raleigh, North Carolina, United States

GSK Investigational Site

Dayton, Ohio, United States

GSK Investigational Site

Garfield Heights, Ohio, United States

GSK Investigational Site

Tulsa, Oklahoma, United States

GSK Investigational Site

Charleston, South Carolina, United States

GSK Investigational Site

Memphis, Tennessee, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Brown Deer, Wisconsin, United States

GSK Investigational Site

Middleton, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23539641 (View on PubMed)

Other Identifiers

113211

Identifier Type: -

Identifier Source: org_study_id