Last updated: 11/03/2018 12:07:00
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed Dose Study Evaluating the Efficacy and Safety of Orvepitant in Subjects with Major Depressive Disorderorvepitant MDD
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Trial overview
Official title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed Dose Study Evaluating the Efficacy and Safety of Orvepitant in Subjects with Major Depressive Disorder
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) total score
Timeframe: Baseline (Day 1) to Week 6
Secondary outcomes:
Percentage of participants with a >= 50 percent (%) reduction from Baseline in HAM-D total score
Timeframe: Baseline (Day 1) to Week 6
Number of participants with (maintained) clinical response
Timeframe: 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)
Timeframe: Baseline (Day 1) to Week 6
Change from Baseline in the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR 16) total score
Timeframe: 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)
Timeframe: Baseline (Day 1) to Week 6
Percentage of participants with Clinical Global Impression- Global Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved)
Timeframe: Up to Week 6
Change from Baseline in the Clinical Global Impression-Severity of Illness (CGI-S) score
Timeframe: Baseline (Day 1) to Week 6
Change from Baseline in the Cognitive and Physical Function Questionnaire (CPFQ) total score
Timeframe: Baseline (Day 1) and Week 6
Change from Baseline in Morning Sleep Questionnaire (MSQ) values for total sleep time (TST), sleep onset latency (SOL) and wake time after sleep onset (WTSO)
Timeframe: Baseline (Day 1) to Week 6
Change from Baseline in MSQ values for number of nocturnal awakenings
Timeframe: Baseline (Day 1) to Week 6
Change from Baseline in MSQ values for sleep quality (SQ) and refreshing value of sleep (RVS)
Timeframe: Baseline (Day 1) to Week 6
Number of participants who remit (have an endpoint HAM-D Total score <= 7) who continue to show symptoms on the HAM-D sleep items
Timeframe: Up to Week 6
Number of participants with suicidal behavior, ideation, and most common ideation using the Columbia Suicidality Severity Rating Scale (C-SSRS)
Timeframe: Week 8
Number of discontinuation-emergent signs and symptoms using the Discontinuation-Emergent Signs and Symptoms (DESS)
Timeframe: Week 1 to Week 8/Follow up 1
Change from Baseline in the Massachusetts Sexual Function Questionnaire (MSFQ)-Males
Timeframe: Baseline (Day 1) to Week 6
Change from Baseline in the MSFQ total score-Females
Timeframe: Baseline (Day 1) to Week 6
Interventions:
Drug: orvepitant
Other: placebo
Enrollment:
328
Observational study model:
Not applicable
Primary completion date:
2010-16-06
Time perspective:
Not applicable
Clinical publications:
Ratti E, Bettica P, Alexander R, Archer G, Carpenter D, Evoniuk G, Gomeni R, Lawson E, Lopez M, Milns H, Rabiner E, Trist D, Trower M, Zamuner S, Krishnan K, Fava M. Full Central NK1 Receptor Blockade is Required for Efficacy in Depression: Evidence from Orvepitant Clinical Studies. J Psychopharmacol. 2013;27(5):424-434.
Medical condition
Depressive Disorder, Major
Product
orvepitant
Collaborators
Not applicable
Study date(s)
March 2009 to June 2010
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 64 years
Accepts healthy volunteers
No
- Subjects must have the ability to comprehend the Informed Consent Form.
- Male or female outpatients, aged 18-64, inclusive.
- 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
Inclusion and exclusion criteria
Inclusion criteria:
- 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
Exclusion criteria:
- 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.
- Subjects who have no contact with an adult on a daily basis. This would exclude subjects who are not living with at least one other adult or subjects who do not have an adult who contacts them on a daily basis.
Trial location(s)
Location
GSK Investigational Site
Orlando, Florida, United States, 32806
Status
Study Complete
Location
GSK Investigational Site
Upland, California, United States, 91786
Status
Study Complete
Location
GSK Investigational Site
Middleton, Wisconsin, United States, 53562
Status
Study Complete
Location
GSK Investigational Site
Lincoln, Rhode Island, United States, 02868
Status
Study Complete
Location
GSK Investigational Site
Beverly Hills, California, United States, 90210
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10029
Status
Study Complete
Location
GSK Investigational Site
Overland Park, Kansas, United States, 66212
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35216
Status
Study Complete
Location
GSK Investigational Site
Arcadia, California, United States, 91007
Status
Study Complete
Location
GSK Investigational Site
National City, California, United States, 91950
Status
Study Complete
Location
GSK Investigational Site
Scottsdale, Arizona, United States, 85251
Status
Study Complete
Location
GSK Investigational Site
Maitland, Florida, United States, 32751
Status
Study Complete
Location
GSK Investigational Site
Seattle, Washington, United States, 98104
Status
Study Complete
Location
GSK Investigational Site
North Miami, Florida, United States, 33161
Status
Study Complete
Location
GSK Investigational Site
Bradenton, Florida, United States, 34208
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2010-16-06
Actual study completion date
2010-16-06
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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