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

NCT03381664 | Completed Phase 1 FDA Drug

• 1 other identifier: 17-AVR-135
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Adult Male and Female Volunteers

Keywords

bioavailability; pharmacokinetics; safety; tolerability; AVP-923; dextromethorphan; quinidine

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (6)

• Number of participants with any adverse event

  3 weeks

• Number of participants with any clinically significant clinical laboratory evaluation

  3 weeks

• Number of participants with any clinically significant physical examination evaluation

  3 weeks

• Number of participants with any clinically significant electrocardiogram evaluation

  3 weeks

• Number of participants with any clinically significant vital sign value

  3 weeks

Study Arms (3)

AVP-923-20/10 capsule

EXPERIMENTAL

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

AVP-923-20/10 via applesauce

EXPERIMENTAL

Participants will receive the contents from a single AVP-923-20/10 capsule mixed and consumed in 1 tablespoon of applesauce.

Drug: AVP-923

AVP-923-20/10 via nasogastric feeding tube

EXPERIMENTAL

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

Interventions

AVP-923 DRUG

capsule

Also known as: Dextromethorphan Hydrobromide and Quinidine Sulfate

AVP-923-20/10 capsule; AVP-923-20/10 via applesauce; AVP-923-20/10 via nasogastric feeding tube

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Avanir Pharmaceuticals: lead

Study Sites (1)

Vince & Associates Clinical Research

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Interventions

dextromethorphan - quinidine combination; Dextromethorphan; Quinidine

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cinchona Alkaloids; Quinuclidines; Quinolines; Heterocyclic Compounds, 2-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 22, 2017
• Study Start: November 28, 2017
• Primary Completion: January 30, 2018
• Study Completion: January 30, 2018
• Last Updated: February 23, 2018

Record last verified: 2018-02

Locations

US (1)