Lofexidine Pharmacokinetics in the Presence of Paroxetine in Healthy Volunteers

NCT02681198 | Completed Phase 1

• 2 other identifiers: USWM-LX1-1010U01DA033276
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy; Lofexidine; Paroxetine; Volunteer

Outcome Measures

Primary Outcomes (6)

• Maximum Plasma Concentration (Cmax)

  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)

  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)

  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)

  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)

  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)

  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 (6)

• Blood pressure (sitting and standing)

  screening; predose and 3.5 and 7.5 hours postdose on Days 1, 13; Day 22.

• 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.

• 12-lead ECGs

  screening; 0 and 6.5 hours postdose on Days 1, 12, 13; Day 22.

• Holter ECGs

  0 (predose), and 3, 4 and 8 hours postdose on Days 1, 12, 13

Study Arms (1)

Lofexidine and paroxetine

EXPERIMENTAL

Lofexidine in the presence of paroxetine

Drug: Lofexidine; Drug: Paroxetine

Interventions

Lofexidine DRUG

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.

Lofexidine and paroxetine

Paroxetine DRUG

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.

Lofexidine and paroxetine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• USWM, LLC (dba US WorldMeds): lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Interventions

lofexidine; Paroxetine

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• George J Atiee, MD

  Worldwide Clinical Trials

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: February 12, 2016
• Study Start: January 1, 2016
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: February 23, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)