A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed Dose Study Evaluating the Efficacy and Safety of Orvepitant in Subjects With Major Depressive Disorder

NCT00880399 | Terminated Phase 2 Results DMC

• 1 other identifier: 111733
• Study Type: interventional
• Target: 328
• Locations: 2 countries
• Sites: 20

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, Major

Keywords

depression; QIDS-SR; HAMD-17; orvepitant; MDD; neurokinin-1 antagonist; double-blind; Phase II; randomized; efficacy; placebo; safety

Outcome Measures

Primary Outcomes (1)

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

  The HAM-D is designed to measure severity of depressive symptoms in participants with primary depressive illness. The scale is a checklist of items (1: depressed mood, 2: feelings of guilt, 3: suicide, insomnia early, 4: insomnia early, 5: insomnia middle, 6: insomnia late, 7: work and activities, 8: retardation, 9: agitation, 10: anxiety psychic item 10: anxiety psychic, item 11: anxiety somatic, item 12: somatic symptoms gastrointestinal, 13: somatic symptoms general, 14: genital symptoms, 15: hypochondriasis, 16: loss of weight and 17: insight) that are ranked on a scale of 0 to 4 or 0 to 2 (4 and 2: highly severe and 0: not present). The HAM-D total score is calculated by summing individual response scores on the HAM-D questionnaire. The highest possible score is 52, representing most severe measure of depression; lowest possible score is 0, representing no depression. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

  Baseline (Day 1) to Week 6

Secondary Outcomes (16)

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

  Baseline (Day 1) to Week 6

• Number of Participants With (Maintained) Clinical Response

  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 HAMD Scale)

  Baseline (Day 1) to Week 6

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

  Baseline (Day 1) to Week 6

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

  Baseline (Day 1) to Week 6

Study Arms (3)

Placebo

PLACEBO COMPARATOR

inactive placebo to match orvepitant 30 and 60 mg dosage forms

Other: placebo

Orvepitant 30 mg

EXPERIMENTAL

30 mg/day (low dose)

Drug: orvepitant

Orvepitant 60 mg

EXPERIMENTAL

60 mg/day (high dose)

Drug: orvepitant

Interventions

orvepitant DRUG

Neurokinin-1 (NK-1) antagonist

Also known as: GW823296

Orvepitant 30 mg; Orvepitant 60 mg

placebo OTHER

inactive placebo to match orvepitant 30 and 60 mg dosage forms

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 (20)

GSK Investigational Site

Birmingham, Alabama, 35216, United States

Location

GSK Investigational Site

Scottsdale, Arizona, 85251, United States

Location

GSK Investigational Site

Arcadia, California, 91007, United States

Location

GSK Investigational Site

Beverly Hills, California, 90210, United States

Location

GSK Investigational Site

National City, California, 91950, United States

Location

GSK Investigational Site

Upland, California, 91786, United States

Location

GSK Investigational Site

Bradenton, Florida, 34208, United States

Location

GSK Investigational Site

Maitland, Florida, 32751, United States

Location

GSK Investigational Site

North Miami, Florida, 33161, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Overland Park, Kansas, 66212, United States

Location

GSK Investigational Site

New York, New York, 10029, United States

Location

GSK Investigational Site

The Bronx, New York, 10467, United States

Location

GSK Investigational Site

Toledo, Ohio, 43623, United States

Location

GSK Investigational Site

Lincoln, Rhode Island, 02868, United States

Location

GSK Investigational Site

Seattle, Washington, 98104, United States

Location

GSK Investigational Site

Middleton, Wisconsin, 53562, United States

Location

GSK Investigational Site

Burlington, Ontario, L7R 4E2, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1C 1T1, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2C4, 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, Major; Depression

Interventions

orvepitant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Limitations and Caveats

The study was terminated early upon recommendation of IDMC that was reviewing data from this trial and two other ongoing trials with same drug. When the trial was terminated 331 participants were 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 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 16, 2010
• Last Updated: September 12, 2017
• Results First Posted: September 12, 2017

Record last verified: 2017-04

Locations

US (17); CA (3)