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
Overview
- Phase
- Phase 1
- Intervention
- AVP-923
- Conditions
- Healthy Adult Male and Female Volunteers
- Sponsor
- Avanir Pharmaceuticals
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Mean time to maximum plasma concentration (Tmax) for the analytes DM, DX, 3-MM, and Q
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
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).
Investigators
Eligibility Criteria
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
Arms & Interventions
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.
Intervention: AVP-923
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.
Intervention: AVP-923
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.
Intervention: AVP-923
Outcomes
Primary Outcomes
Mean time to maximum plasma concentration (Tmax) for the analytes DM, DX, 3-MM, and Q
Time Frame: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Secondary Outcomes
- Number of participants with any clinically significant electrocardiogram evaluation(3 weeks)
- Number of participants with any clinically significant physical examination evaluation(3 weeks)
- 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 vital sign value(3 weeks)
- Number of participants with the indicated score on the Columbia-Suicide Severity Rating Scale (C-SSRS)(3 weeks)