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

• ClinicalTrials.gov Identifier: NCT02153502
• Recruitment Status: Completed
• First Posted: June 3, 2014
• Last Update Posted: May 15, 2017
• Sponsor: Avanir Pharmaceuticals
• Information provided by (Responsible Party): Avanir Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Depressive Disorder, Treatment-Resistant	Drug: AVP-786 (d6-dextromethorphan hydrobromide and quinidine sulfate combination); Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: 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
• Actual Study Start Date: July 2014
• Actual Primary Completion Date: February 2016
• Actual Study Completion Date: February 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: AVP-786	Drug: AVP-786 (d6-dextromethorphan hydrobromide and quinidine sulfate combination); AVP-786 capsules administered twice a day over a 10-week period
Placebo Comparator: Placebo	Drug: Placebo; Placebo capsules administered twice a day over a 10-week period

Outcome Measures

Primary Outcome Measures :

1. Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score [ Time Frame: Visit 5 (Day 70) Week 10 ]
   Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score in patients receiving AVP 786 compared with patients administered placebo

Secondary Outcome Measures :

1. 17-item Hamilton Rating Scale for Depression (HAM-D17) [ Time Frame: Visit 5 (Day 70) Week 10 ]
2. Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ) [ Time Frame: Visit 5 (Day 70) Week 10 ]
3. 16-item Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR16) [ Time Frame: Visit 5 (Day 70) Week 10 ]
4. Sheehan Disability Scale (SDS) [ Time Frame: Visit 5 (Day 70) Week 10 ]
5. Clinical Global Impression of Severity of Illness (CGI-S) [ Time Frame: Visit 5 (Day 70) Week 10 ]
6. Clinical Global Impression of Change (CGI-C) [ Time Frame: Visit 5 (Day 70) Week 10 ]
7. EuroQOL 5 Dimension 5 Level (EQ-5D-5L) [ Time Frame: Visit 5 (Day 70) Week 10 ]
8. Patient Global Impression of Change (PGIC) [ Time Frame: Visit 5 (Day 70) Week 10 ]
9. 7-item Generalized Anxiety Disorder (GAD-7) [ Time Frame: Visit 5 (Day 70) Week 10 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

Birmingham, Alabama, United States, 35213

Birmingham, Alabama, United States, 35294

United States, California

Bellflower, California, United States, 90706

Costa Mesa, California, United States, 92626

Garden Grove, California, United States, 92845

Lomita, California, United States, 90717

Oceanside, California, United States, 92056

Riverside, California, United States, 92506

Santa Ana, California, United States, 92706

Sherman Oaks, California, United States, 91403

United States, Colorado

Denver, Colorado, United States, 80239

United States, Florida

Bradenton, Florida, United States, 34201

Jacksonville, Florida, United States, 32256

Miami, Florida, United States, 33155

Orange City, Florida, United States, 32763

Orlando, Florida, United States, 32801

United States, Georgia

Decatur, Georgia, United States, 30030

United States, Illinois

Hoffman Estates, Illinois, United States, 60169

United States, Indiana

Valparaiso, Indiana, United States, 46383

United States, Maryland

Baltimore, Maryland, United States, 21285

Glen Burnie, Maryland, United States, 21061

United States, Massachusetts

Boston, Massachusetts, United States, 02131

United States, New York

Brooklyn, New York, United States, 11241

New York, New York, United States, 10003

Staten Island, New York, United States, 10312

United States, Ohio

Garfield Heights, Ohio, United States, 44125

United States, Oklahoma

Oklahoma City, Oklahoma, United States, 73103

Oklahoma City, Oklahoma, United States, 73112

Tulsa, Oklahoma, United States, 74101

United States, Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Philadelphia, Pennsylvania, United States, 19139

United States, Utah

Murray, Utah, United States, 84123

Sponsors and Collaborators

Avanir Pharmaceuticals

More Information

• Responsible Party: Avanir Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02153502
• Other Study ID Numbers: 14-AVP-786-201
• First Posted: June 3, 2014
• Last Update Posted: May 15, 2017
• Last Verified: May 2017

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Mood Disorders; Mental Disorders; Behavioral Symptoms; Quinidine; Quinidine gluconate; Dextromethorphan; Antitussive Agents; Respiratory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Anti-Arrhythmia Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Enzyme Inhibitors; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Voltage-Gated Sodium Channel Blockers