Lofexidine Pharmacokinetics in the Presence of Paroxetine, a Strong CYP2D6 Inhibitor, in Healthy Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Maximum Plasma Concentration (Cmax)
Study Overview
Brief Summary
The purpose of this study is to determine the pharmacokinetics, safety and tolerability of lofexidine HCl in the presence of paroxetine in healthy adults.
Detailed Description
This is a Phase 1, open-label, single-sequence study to determine the pharmacokinetics, safety and tolerability of lofexidine HCl in the presence of paroxetine in healthy adults. Lofexidine HCl is an alpha-2 adrenergic agonist under development for the treatment of acute withdrawal from short-acting opioids. Paroxetine HCl is an orally administered psychotropic drug indicated in the treatment of major depressive, obsessive compulsive, panic, social anxiety, and generalized anxiety disorders. Paroxetine is a strong CYP2D6 inhibitor.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subject is between ages of 18 to 60 years at enrollment with a body mass index (BMI) between 18 and 35 kg/m
- •Female subjects must not be lactating, and must either a) be postmenopausal or b) agree to use an acceptable form of birth control from screening until 14 days after completion of the study.
- •Subject is in good health based on medical history, physical exam, laboratory profile, and electrocardiogram (ECG) as judged by the Investigator.
- •If subject smokes, subject agrees to limit smoking while in the study to not more than 10 cigarettes per day.
Exclusion Criteria
- •History of suicidal ideations or depression requiring professional intervention including counseling or antidepressant medication over the past 12 months.
- •History or presence of allergic or adverse response to lofexidine, paroxetine, or related drugs.
- •Received any drugs capable of inhibiting CYP enzymes CYP1A2, CYP2C19, or CYP2D6 within 14 days or 5 half-lives (whichever is more) before Day
- •Consumes more than 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) or has a significant history of alcohol abuse or drug/chemical abuse within the last 1 year.
- •Has a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Arms & Interventions
Lofexidine and paroxetine
Lofexidine in the presence of paroxetine
Intervention: Lofexidine (Drug)
Lofexidine and paroxetine
Lofexidine in the presence of paroxetine
Intervention: Paroxetine (Drug)
Outcomes
Primary Outcomes
Maximum Plasma Concentration (Cmax)
Time Frame: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Apparent Terminal Elimination Half-life (T½)
Time Frame: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Area Under the Curve from Time Zero to Infinity (AUC 0-infinity)
Time Frame: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Apparent Clearance (CL/F)
Time Frame: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Time to Maximum Plasma Concentration (Tmax)
Time Frame: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Area Under the Concentration-Time Curve from Time Zero to Last Quantified Concentration (AUC 0-t)
Time Frame: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Secondary Outcomes
- Heart rate (sitting and standing)(screening; predose and 3.5 and 7.5 hours postdose on Days 1 and 13; Day 22.)
- Laboratory Assessments(screening; Day -1, 2, 12, 14; Day 22.)
- Holter ECGs(0 (predose), and 3, 4 and 8 hours postdose on Days 1, 12, 13)
- Columbia Suicide Severity Rating Scale (C-SSRS)(screening; Days 7, 13, 22, 50.)
- 12-lead ECGs(screening; 0 and 6.5 hours postdose on Days 1, 12, 13; Day 22.)
- Blood pressure (sitting and standing)(screening; predose and 3.5 and 7.5 hours postdose on Days 1, 13; Day 22.)