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

Healthy Adult Male and Female Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03381664
• Other study ID #: 17-AVR-135
• Status: Completed
• Phase: Phase 1
• First received: December 18, 2017
• Last updated: February 21, 2018
• Start date: November 28, 2017
• Est. completion date: January 30, 2018

Study information

• Verified date: February 2018
• Source: Avanir Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: January 30, 2018
• Est. primary completion date: January 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Adult Male and Female Volunteers

Intervention

Drug:
• AVP-923
capsule

Locations

Country	Name	City	State
United States	Vince & Associates Clinical Research	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Avanir Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Number of participants with any adverse event		3 weeks
Secondary	Number of participants with any clinically significant clinical laboratory evaluation	Clinical significance will be determined by the Investigator.	3 weeks
Secondary	Number of participants with any clinically significant physical examination evaluation	Clinical significance will be determined by the Investigator.	3 weeks
Secondary	Number of participants with any clinically significant electrocardiogram evaluation	Clinical significance will be determined by the Investigator.	3 weeks
Secondary	Number of participants with any clinically significant vital sign value	Clinical significance will be determined by the Investigator.	3 weeks
Secondary	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