Clinical trial NCT02681198: Lofexidine Pharmacokinetics in the Presence of Paroxetine in Healthy Volunteers
Official title: Lofexidine Pharmacokinetics in the Presence of Paroxetine, a Strong CYP2D6 Inhibitor, in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Lofexidine
Paroxetine
Volunteer
Lead sponsor: USWM, LLC (dba US WorldMeds)
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2016-02-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Subject is between ages of 18 to 60 years at enrollment with a body mass index (BMI) between 18 and 35 kg/m2.
* 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 1.
* 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.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 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.
measure: Time to Maximum Plasma Concentration (Tmax)
timeFrame: 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.
measure: Apparent Terminal Elimination Half-life (T½)
timeFrame: 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.
measure: Area Under the Concentration-Time Curve from Time Zero to Last Quantified Concentration (AUC 0-t)
timeFrame: 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.
measure: Area Under the Curve from Time Zero to Infinity (AUC 0-infinity)
timeFrame: 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.
measure: Apparent Clearance (CL/F)
timeFrame: 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:
measure: Blood pressure (sitting and standing)
timeFrame: screening; predose and 3.5 and 7.5 hours postdose on Days 1, 13; Day 22.
measure: Heart rate (sitting and standing)
timeFrame: screening; predose and 3.5 and 7.5 hours postdose on Days 1 and 13; Day 22.
measure: Laboratory Assessments
timeFrame: screening; Day -1, 2, 12, 14; Day 22.
measure: 12-lead ECGs
timeFrame: screening; 0 and 6.5 hours postdose on Days 1, 12, 13; Day 22.
measure: Holter ECGs
timeFrame: 0 (predose), and 3, 4 and 8 hours postdose on Days 1, 12, 13
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: screening; Days 7, 13, 22, 50.
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
affiliation: Worldwide Clinical Trials
name: George J Atiee, MD
role: PRINCIPAL_INVESTIGATOR
References: