A Randomised, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Orvepitant in Subjects With Major Depressive Disorder

NCT00880048 | Terminated Phase 2 Results DMC

• 1 other identifier: 110833
• Study Type: interventional
• Target: 343
• Locations: 2 countries
• Sites: 32

Brief Summary

This is a 6-week, randomised, multicenter, double-blind, placebo controlled, fixed dose parallel group study to assess the efficacy and safety of orvepitant (30 and 60 mg/day) versus placebo in subjects with a diagnosis of a Major Depressive Disorder, 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 randomised at the baseline visit to receive either orvepitant 30mg/day, orvepitant 60mg/day or placebo (equal chance of receiving any of the three possible treatments, i.e., a 1:1:1 ratio) for a six-week double-blind treatment phase. Those subjects randomised to receive placebo will receive study medication identical in appearance to that received by subjects assigned to receive orvepitant 30 or 60mg/day. Efficacy will be assessed via standard depression symptom and severity rating scales or questionaires. The Hamilton Depression Rating Scale (HAM-D) will be used as the primary measure. Secondary efficacy endpoints include the Quick Inventory of Depressive Symptomatology (QIDS-SR) and the Clinical Global Impression- Global Improvement and Severity of Illness Scale (CGI-I and CGI-S, respectively). 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

Depressive Disorder

Keywords

depression; safety; HAMD; QIDS-SR; NK-1 antagonist; efficacy; orvepitant; placebo; MDD; video-rating

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) Total Score

  HAM-D was use to measure the severity of depressive symptoms in participants with primary depressive illness. It was a checklist of items that were ranked on a scale of 0-4 or 0-2. Items with quantifiable severity were scored 0 (lowest severity) to 4 (greatest severity); The HAM-D total score was calculated by summing the individual response scores. The lowest possible score was 0 (absence of depression) and the highest possible score was 52 (most severe measure of depression). For the last observation carried forward analyses, the most recent post randomization total score (as opposed to individual responses) was "carried forward" and used in the calculation of the change from randomization (Baseline) value. If the responses to more than 1 question were missing for a participant at a particular time point, the total score was not calculated. Change from Baseline in total score was the difference between HAM-D total score at the time point being analyzed and randomization.

  Baseline and up to Week 6

Secondary Outcomes (16)

• Percentage of Participants With a >=50% Reduction From Baseline in HAM-D Total Score

  Up to Week 6

• Number of Participants Who Maintained Clinical Response by Week 6

  Up to Week 6

• Change From Baseline in the Bech Melancholia Scale Total Score (Sum of Items 1, 2, 7, 8, 10, and 13 of the 17-item HAM-D Scale)

  Baseline and up to Week 6

• Change From Baseline in the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR 16) Total Score

  Baseline and up to Week 6

• Change From Baseline in the HAM-D Anxiety Factor Score (Sum of Items 10, 11, 12, 13, 15 and 17)

  Baseline and up to Week 6

Study Arms (3)

orvepitant 30 mg

EXPERIMENTAL

orvepitant 30 mg (low dose)

Drug: orvepitant

orvepitant 60 mg

EXPERIMENTAL

orvepitant 60 mg (high dose)

Drug: orvepitant

Placebo

PLACEBO COMPARATOR

inactive placebo to match orvepitant 30 mg and 60 mg dosage forms

Other: Placebo

Interventions

orvepitant DRUG

neurokinin-1 antagonist

Also known as: GW823296

orvepitant 30 mg; orvepitant 60 mg

Placebo OTHER

Placebo to match orvepitant 30 mg and 60 mg

Placebo

Eligibility Criteria

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

You may qualify if:

• Subjects must have the ability to comprehend the Informed Consent Form.
• Male or female outpatients, aged 18-64, inclusive.
• A primary diagnosis of major depressive disorder, single episode or recurrent.
• Subjects must, in the investigator's opinion and based on the subject's history, have met depression criteria for at least 8 weeks prior to the Screening Visit.
• Subjects with symptom severity considered to be at least moderate to severe by the investigator.
• Women of childbearing potential are only eligible IF they commit to consistent and correct use of an acceptable method of birth control that must be documentation at each visit

You may not qualify if:

• Subjects whose mood-related symptoms are better accounted for by a diagnosis other than depression; subjects diagnosed with Alzheimer's Disease or other form of 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 with any history of a significant abnormality of the neurological system (including dementia and other cognitive disorders or significant head injury) or any history of seizures (convulsions).
• Subjects have a positive urine test at screening for illegal drug use and/or who have a history of substance abuse or dependence (alcohol or drugs) within the past 12 months.
• Subjects who are currently receiving regularly scheduled psychotherapy (individual or group), plan to start psychotherapy during the trial or have received regularly scheduled psychotherapy during the 12 week period prior to the Screening Visit.
• Subjects who have a history of failing to respond to adequate treatment with an antidepressant, i..e, failure to improve following administration of at least two other antidepressants, each given for at least 4 weeks.
• Subjects who, in the investigator's judgement, pose a homicidal or serious suicidal risk, have made a suicide attempt within the 6 months preceding screening or who have ever been homicidal.
• Subjects who have received the following treatments for depression in the past: electroconvulsive therapy (ECT), vagal stimulation, or transcranial magnetic stimulation (TMS) within the 6 months prior to the Screening Visit.
• Subjects with an unstable medical disorder; or with a disorder that otherwise would likely interfere with the activity of the study medication (orvepitant).
• Subjects have any screening laboratory abnormality that in the investigator's judgement is considered to be clinically significant.
• Subjects with an abnormal thyroid test at the Screening Visit. Subjects maintained on thyroid medication must have normal thyroid levels for a period of at least six months prior to the Screening Visit.
• Subjects have any screening electrocardiography (ECG) finding that in the investigator's judgement is considered to be clinically significant.
• Women who have a positive pregnancy test at the Screening Visit, a positive urine dipstick test at the Baseline (Randomization) Visit, or who are lactating or planning to become pregnant within the 4 months following the Screen Visit.
• Subjects who have taken other psychoactive drugs within two weeks prior to the Baseline Visit i.e. at any time during the Screening period. This includes "over-the-counter" psychoactive medications such as St. John's Wort and SAM-e.
• Subjects who have taken other drugs within 2 weeks prior to the Baseline visit which the investigator feels may interact with the study medication.
• Subjects who are currently participating in another clinical trial in which the subject is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month for studies unrelated to depression, or 6 months for studies related to depression.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (32)

GSK Investigational Site

Phoenix, Arizona, 85020, United States

Location

GSK Investigational Site

Little Rock, Arkansas, 72223, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

Denver, Colorado, 80239, United States

Location

GSK Investigational Site

Norwich, Connecticut, 06360, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32216, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Winter Park, Florida, 32789, United States

Location

GSK Investigational Site

Springfield, Illinois, 62711, United States

Location

GSK Investigational Site

Rockville, Maryland, 20852, United States

Location

GSK Investigational Site

Weymouth, Massachusetts, 02190, United States

Location

GSK Investigational Site

Saint Charles, Missouri, 63301, United States

Location

GSK Investigational Site

Willingboro, New Jersey, 08046, United States

Location

GSK Investigational Site

Brooklyn, New York, 11235, United States

Location

GSK Investigational Site

Dayton, Ohio, 45408, United States

Location

GSK Investigational Site

Garfield Heights, Ohio, 44125, United States

Location

GSK Investigational Site

Portland, Oregon, 97210, United States

Location

GSK Investigational Site

Salem, Oregon, 97301, United States

Location

GSK Investigational Site

Emmaus, Pennsylvania, 18049, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19131, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19139, United States

Location

GSK Investigational Site

Columbia, South Carolina, 29201, United States

Location

GSK Investigational Site

Austin, Texas, 78756, United States

Location

GSK Investigational Site

Dallas, Texas, 75231, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229-3815, United States

Location

GSK Investigational Site

Charlottesville, Virginia, 22903, United States

Location

GSK Investigational Site

Milwaukee, Wisconsin, 53226, United States

Location

GSK Investigational Site

Penticton, British Columbia, V2A 4M4, Canada

Location

GSK Investigational Site

Miramichi, New Brunswick, E1V 6X3, Canada

Location

GSK Investigational Site

Sydney, Nova Scotia, B1S 2E8, Canada

Location

GSK Investigational Site

Mississauga, Ontario, L5M 4N4, Canada

Location

GSK Investigational Site

Gatineau, Quebec, J9A 1K7, Canada

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

Depressive Disorder; Depression

Interventions

orvepitant

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Limitations and Caveats

The study was terminated early upon the recommendation of an Independent Data Monitoring Committee. At the time the trial was terminated 343 participants had been randomized, compared to a target of 348 participants.

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: April 9, 2009
• First Posted: April 13, 2009
• Study Start: March 11, 2009
• Primary Completion: June 21, 2010
• Study Completion: June 21, 2010
• Last Updated: October 13, 2017
• Results First Posted: October 13, 2017

Record last verified: 2017-08

Locations

US (27); CA (5)