Clinical trial NCT02153502: Efficacy, Safety, and Tolerability Study of AVP-786 as an Adjunctive Therapy in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deuterium Modified Dextromethorphan Hydrobromide/Quinidine Sulfate) as an Adjunctive Therapy in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Treatment-Resistant
Lead sponsor: Avanir Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-06-03
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this 10-week study are to evaluate the efficacy, safety, and tolerability of AVP 786 as an adjunctive therapy compared with placebo in patients with major depressive disorder (MDD) who have shown an inadequate response to standard antidepressant treatment. A secondary objective of this study is to assess the pharmacokinetics (PK) of AVP-786 and potential correlations with pharmacodynamic effects.

Detailed description: It is estimated that up to approximately 200 patients will participate in the study at approximately 30 enrolling centers in the US.

Eligible patients for this study must have MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria, and have shown an inadequate response to standard antidepressant treatment.

This is a multicenter, randomized, double-blind, placebo-controlled, study of 10 weeks duration.

Following screening procedures for assessment of inclusion and exclusion criteria, eligible patients will be randomized into the study. Study medication will be administered orally twice a day (BID) (1 capsule in the morning and 1 capsule in the evening, approximately 12 hours apart) throughout the treatment period.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of major depressive episode ≤ 24 months in duration
* HAM-D17 score ≥ 20.
* Documented to not have a significant (25% or greater) change in QIDS-SR16 score between Screening and Baseline visits.
* Patients have been deemed to have an inadequate response (less than 50% symptom reduction) to at least 1 but no more than 3 adequate antidepressant trials during the current depressive episode.
* Patients must be receiving ongoing treatment with an adequate dose of antidepressants.
* Body Mass Index (BMI) of 18-35 kg/m².

Exclusion Criteria:

* History of myasthenia gravis.
* Have cardiovascular concerns such as:

  * History of complete heart block, QT interval corrected for heart rate (QTc) prolongation, or torsades de pointes.
  * QTc using the Fridericia's formula (QTcF) at screening \> 450 msec for males and \> 470 msec for females based on central review at the screening visit, unless due to ventricular pacing.
  * Any family history of congenital QT interval prolongation syndrome.
* Known hypersensitivity/intolerance to DM, Q, opiate drugs (codeine, etc.), or any other ingredient of the study medication.
* Pose a current suicide risk, as evidenced by any of the following:

  * It is the judgment of the investigator that the subject may be at risk for suicide.
  * The subject is rated a "yes" to question 4 or question 5 on the Baseline C-SSRS, if the most recent episode occurred within the past 12 months.
  * The subject has attempted suicide within the past 6 months
* Presence of any other current DSM-IV-TR Axis I disorders with the exception of: generalized anxiety disorder (GAD: 300.02), social anxiety disorder (300.23), dysthymic disorder (300.4), or specific phobia (300.29). Patients with co-morbid GAD, social anxiety disorder, or specific phobia are ineligible if the co-morbid condition is clinically unstable, or has been the primary focus of treatment within the 6 month period prior to screening
* Axis I diagnosis of:

  * Delirium, dementia, amnestic, or other cognitive disorder;
  * Schizophrenia or other psychotic disorder, based on the M.I.N.I.;
  * Bipolar I or II disorder, based on the M.I.N.I.
* Clinically significant Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.

Primary outcomes:
measure: Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score
timeFrame: Visit 5 (Day 70) Week 10
Secondary outcomes:
measure: 17-item Hamilton Rating Scale for Depression (HAM-D17)
timeFrame: Visit 5 (Day 70) Week 10
measure: Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ)
timeFrame: Visit 5 (Day 70) Week 10
measure: 16-item Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR16)
timeFrame: Visit 5 (Day 70) Week 10
measure: Sheehan Disability Scale (SDS)
timeFrame: Visit 5 (Day 70) Week 10
measure: Clinical Global Impression of Severity of Illness (CGI-S)
timeFrame: Visit 5 (Day 70) Week 10
measure: Clinical Global Impression of Change (CGI-C)
timeFrame: Visit 5 (Day 70) Week 10
measure: EuroQOL 5 Dimension 5 Level (EQ-5D-5L)
timeFrame: Visit 5 (Day 70) Week 10
measure: Patient Global Impression of Change (PGIC)
timeFrame: Visit 5 (Day 70) Week 10
measure: 7-item Generalized Anxiety Disorder (GAD-7)
timeFrame: Visit 5 (Day 70) Week 10
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Bellflower
country: United States
state: California
city: Costa Mesa
country: United States
state: California
city: Garden Grove
country: United States
state: California
city: Lomita
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Riverside
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Sherman Oaks
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Bradenton
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orange City
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Hoffman Estates
country: United States
state: Illinois
city: Valparaiso
country: United States
state: Indiana
city: Baltimore
country: United States
state: Maryland
city: Glen Burnie
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Brooklyn
country: United States
state: New York
city: New York
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Garfield Heights
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Murray
country: United States
state: Utah
Study officials:
References: