The purpose of this study is to determine the pharmacokinetics, safety and tolerability of lofexidine HCl in the presence of paroxetine in healthy adults.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
All subjects will receive two single doses of lofexidine HCl; one 0.4 mg dose taken alone on Day 1 and one 0.4 mg dose taken with 40 mg once daily paroxetine HCl at steady-state on Day 13.
All subjects will receive daily single doses of paroxetine HCl; one 20 mg dose taken Days 4-6, one 40 mg dose taken Days 7-19, one 20 mg dose taken Day 20, one 10 mg dose taken Days 21-22.
Worldwide Clinical Trials
San Antonio, Texas, United States
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.
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.
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 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.
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.
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Blood pressure (sitting and standing)
Time frame: screening; predose and 3.5 and 7.5 hours postdose on Days 1, 13; Day 22.
Heart rate (sitting and standing)
Time frame: screening; predose and 3.5 and 7.5 hours postdose on Days 1 and 13; Day 22.
Laboratory Assessments
Measurements in hematology, blood chemistry, coagulation, and urinalysis parameters will be examined. Labs will be done at screening, and at Days -1, 2,12,14, 22.
Time frame: screening; Day -1, 2, 12, 14; Day 22.
12-lead ECGs
Time frame: screening; 0 and 6.5 hours postdose on Days 1, 12, 13; Day 22.
Holter ECGs
Time frame: 0 (predose), and 3, 4 and 8 hours postdose on Days 1, 12, 13
Columbia Suicide Severity Rating Scale (C-SSRS)
Time frame: screening; Days 7, 13, 22, 50.