Study to Assess the Bioavailability, Pharmacokinetics, Safety, and Tolerability of AVP-923 in Healthy Adult Participants

A Phase 1, Randomized, Single-Dose, 3-Way, Crossover Study to Compare the Relative Bioavailability, Pharmacokinetics, Safety and Tolerability of AVP-923 (Dextromethorphan Hydrobromide and Quinidine Sulfate Capsules) Administered in Applesauce or Via a Nasogastric Feeding Tube With Administration of a Capsule in Healthy Adult Subjects

This study will be conducted to evaluate the relative bioavailability, pharmacokinetics, safety, and tolerability of AVP-923 (dextromethorphan hydrobromide [DM] and quinidine sulfate [Q] capsules) when the contents of a capsule are administered in applesauce or via a nasogastric feeding tube, compared with administration of a capsule in healthy, fasting, adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Male and Female Volunteers
• Intervention / Treatment: Drug: AVP-923

Detailed Description

This is an open-label, single-center, randomized, single-dose, 3-treatment, 3-period, 6-sequence crossover study in healthy adult participants consisting of approximately 7 weeks of treatment. The study population will be limited to extensive metabolizers of cytochrome P450 (CYP) 2D6.

Approximately 18 participants will be randomly assigned to 1 of 6 sequences (ABC, ACB, BAC, BCA, CAB, CBA).

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince & Associates Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adults, 18 to 65 years of age, inclusive
• Willing to sign informed consent form
• Cytochrome P450 2D6 genotype that confers extensive metabolizer profile (as per documented phenotype interpretation from local laboratory and approval from Avanir)

Exclusion Criteria:

• History or presence of significant pulmonary, hepatic, renal, hematologic, allergic, endocrine (including diabetes), immunologic, dermatologic, neurologic (including history or presence of seizures or convulsive disorders), psychiatric disease (including history of suicidal ideation or behavior) or any eating disorder deemed clinically significant by the investigator
• History or presence of significant cardiovascular disease, including complete heart block, QT interval corrected for heart rate (QTc) prolongation, and/or torsades de pointes
• History or presence of any gastrointestinal (GI) disease or condition that could compromise participant safety or affect the absorption of study drug, including GI ulcers, GI bleeding, esophageal or gastric varices, and dyspepsia requiring regular (i.e., more frequently than once a month) use of acid-reducing drugs
• Known hypersensitivity/intolerance to dextromethorphan or quinidine
• Participants whom the principal investigator or his delegate deems to be ineligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVP-923-20/10 capsule; Participants will receive a single AVP-923-20/10 (dextromethorphan hydrobromide [DM] 20 milligram [mg]/quinidine sulfate [Q] 10 mg) capsule administered orally.	Drug: AVP-923; capsule; Other Names: Dextromethorphan Hydrobromide and Quinidine Sulfate
Experimental: AVP-923-20/10 via applesauce; Participants will receive the contents from a single AVP-923-20/10 capsule mixed and consumed in 1 tablespoon of applesauce.	Drug: AVP-923; capsule; Other Names: Dextromethorphan Hydrobromide and Quinidine Sulfate
Experimental: AVP-923-20/10 via nasogastric feeding tube; Participants will receive the contents from a single AVP-923-20/10 capsule solubilized in feeding solution and administered through a nasogastric feeding tube.	Drug: AVP-923; capsule; Other Names: Dextromethorphan Hydrobromide and Quinidine Sulfate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean area under the concentration time curve (AUC) from time 0 to time of last measurable concentration (AUC0-t) for the analytes dextromethorphan (DM), dextrorphan (DX), 3-methoxymorphinan (3-MM), and quinidine (Q)	pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean AUC from time 0 to infinity (AUC0-inf) for the analytes DM, DX, 3-MM, and Q	pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean maximum plasma concentration (Cmax) for the analytes DM, DX, 3-MM, and Q	pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean time to maximum plasma concentration (Tmax) for the analytes DM, DX, 3-MM, and Q	pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean apparent terminal elimination half-life (t1/2) for the analytes DM, DX, 3-MM, and Q	pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Mean apparent elimination rate constant (kel) for the analytes DM, DX, 3-MM, and Q	pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with any adverse event		3 weeks
Number of participants with any clinically significant clinical laboratory evaluation	Clinical significance will be determined by the Investigator.	3 weeks
Number of participants with any clinically significant physical examination evaluation	Clinical significance will be determined by the Investigator.	3 weeks
Number of participants with any clinically significant electrocardiogram evaluation	Clinical significance will be determined by the Investigator.	3 weeks
Number of participants with any clinically significant vital sign value	Clinical significance will be determined by the Investigator.	3 weeks
Number of participants with the indicated score on the Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS will be used to prospectively assess suicidal ideation (intensity rated from 1 [low severity] to 5 [high severity]) and behavior throughout the study.	3 weeks

Collaborators and Investigators

• Sponsor: Avanir Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): January 30, 2018
• Study Completion (Actual): January 30, 2018

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 22, 2017

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; bioavailability; dextromethorphan; AVP-923; quinidine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Membrane Transport Modulators; Cytochrome P-450 Enzyme Inhibitors; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Respiratory System Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Antitussive Agents; Adrenergic alpha-Antagonists; Dextromethorphan; Quinidine
• Other Study ID Numbers: 17-AVR-135

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No