A Phase 1, Randomized, Double-blind, Crossover Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of QEV-817 Oral Suspension in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Hydrocodone Bitartrate
- Conditions
- Healthy
- Sponsor
- Quivive Pharma, Inc.
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
- Status
- Not Yet Recruiting
- Last Updated
- last year
Overview
Brief Summary
This study has been designed to assess the safety, tolerability, and pharmacokinetics of a therapeutic dose of hydrocodone bitartrate with and without an oral dose of doxapram hydrochloride in healthy volunteers who are naltrexone-blocked.
Detailed Description
This is a Phase 1, single-center, double-blind, randomized crossover study that will be conducted in male and female healthy volunteers. The study will be conducted at a single site in the US. The study consists of a 28-day Screening Period, a four-day treatment period, and a one-day safety follow-up period. The study will be conducted in eight (8) healthy male and female subjects. Up to an additional five (5) subjects may be enrolled as alternates to replace dropouts. Subjects will be randomized (1:1) to one of two crossover treatment sequences. The subjects, Investigators, and site personnel (except site personnel responsible for study treatment preparation) will be blinded to treatment assignments. Subjects will receive either a fixed therapeutic dose of oral hydrocodone alone or in combination with a fixed dose of oral doxapram. Prior to treatment, all subjects will receive naltrexone (opioid antagonist) to block opioid effects (i.e., naltrexone block). Safety will be evaluated by monitoring the nature, severity, and incidence of adverse events (AEs); and changes from baseline in physical examination, vital signs, 12-lead electrocardiogram (ECG) assessment, pulse oximetry, and clinical laboratory tests. Pharmacokinetics of both drugs and their primary metabolites will be assessed in plasma samples collected through 24 hours post-dose from all subjects. All enrolled subjects will also be genotyped for CYP2D6 polymorphism status.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Sequence A - Hydrocodone alone followed by combined (hydrocodone + doxapram)
Subjects randomized to Sequence A will first receive a single oral administration of hydrocodone bitartrate alone on Study Day-2 and then receive a combination of hydrocodone bitartrate and doxapram hydrocholoride on study Day-4 (after a 48 hour wash-out).
Intervention: Hydrocodone Bitartrate
Sequence A - Hydrocodone alone followed by combined (hydrocodone + doxapram)
Subjects randomized to Sequence A will first receive a single oral administration of hydrocodone bitartrate alone on Study Day-2 and then receive a combination of hydrocodone bitartrate and doxapram hydrocholoride on study Day-4 (after a 48 hour wash-out).
Intervention: Doxapram Hydrochloride
Sequence B - Combined (hydrocodone + doxapram) followed by hydrocodone alone
Subjects randomized to Sequence B will first receive a single combined administration of hydrocodone bitartrate and doxapram hydrocholoride on Study Day-2 and then receive hydrocodone alone on study Day-4 (after a 48 hour wash-out).
Intervention: Hydrocodone Bitartrate
Sequence B - Combined (hydrocodone + doxapram) followed by hydrocodone alone
Subjects randomized to Sequence B will first receive a single combined administration of hydrocodone bitartrate and doxapram hydrocholoride on Study Day-2 and then receive hydrocodone alone on study Day-4 (after a 48 hour wash-out).
Intervention: Doxapram Hydrochloride
Outcomes
Primary Outcomes
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Day 1 to Day 5
Incidence, nature, and severity of TEAEs
Number of Participants with Abnormal Laboratory Assessments, 12-Lead Electrocardiogram (ECG), and Vital Signs
Time Frame: Day 1 to Day 5
Changes from baseline in physical examination, vital signs, 12-lead ECG assessment and pulse oximetry
Secondary Outcomes
- Plasma PK Parameters (Tmax)(Day 2 and Day 4)
- Plasma PK Parameters (Cmax)(Day 2 and Day 4)
- Plasma PK Parameters (AUC0-inf)(Day 2 and Day 4)