Clinical trial NCT03381664: Study to Assess the Bioavailability, Pharmacokinetics, Safety, and Tolerability of AVP-923 in Healthy Adult Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Male and Female Volunteers
Keywords: bioavailability
pharmacokinetics
safety
tolerability
AVP-923
dextromethorphan
quinidine
Lead sponsor: Avanir Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-12-22
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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).

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

Primary outcomes:
measure: 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)
timeFrame: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
measure: Mean AUC from time 0 to infinity (AUC0-inf) for the analytes DM, DX, 3-MM, and Q
timeFrame: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
measure: Mean maximum plasma concentration (Cmax) for the analytes DM, DX, 3-MM, and Q
timeFrame: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
measure: Mean time to maximum plasma concentration (Tmax) for the analytes DM, DX, 3-MM, and Q
timeFrame: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
measure: Mean apparent terminal elimination half-life (t1/2) for the analytes DM, DX, 3-MM, and Q
timeFrame: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
measure: Mean apparent elimination rate constant (kel) for the analytes DM, DX, 3-MM, and Q
timeFrame: pre-dose (within 30 minutes prior to dosing) and post-dose (up to 48 hours after drug administration)
Secondary outcomes:
measure: Number of participants with any adverse event
timeFrame: 3 weeks
measure: Number of participants with any clinically significant clinical laboratory evaluation
timeFrame: 3 weeks
measure: Number of participants with any clinically significant physical examination evaluation
timeFrame: 3 weeks
measure: Number of participants with any clinically significant electrocardiogram evaluation
timeFrame: 3 weeks
measure: Number of participants with any clinically significant vital sign value
timeFrame: 3 weeks
measure: Number of participants with the indicated score on the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Vince & Associates Clinical Research
state: Kansas
Study officials:
References: