Assessment of the Effect of Naltrexone on Lofexidine Single Dose Pharmacokinetics in Healthy Subjects

NCT02446002 | Completed Phase 1

• 2 other identifiers: USWM-LX1-10091R01DA030916
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1, open-label, single-arm study with two single doses of lofexidine and multiple doses of naltrexone in healthy adult subjects to determine the effect of naltrexone on the single dose pharmacokinetics of the oral lofexidine formulation.

Conditions

Healthy

Keywords

Volunteer

Outcome Measures

Primary Outcomes (2)

• PK Profile for Lofexidine only: Cmax, Tmax, AUC, AUC 0-24, AUC 0-t, AUC 0-infinity, λz, and CL/F

  Descriptive statistics will be used to summarize lofexidine concentrations at each time point and PK parameters by treatment phase.Comparisons will be made between Day 1 and Day 11 for Cmax, AUC0-24, AUC0-t, AUC0-∞, Tmax, and t1/2

  Day 1 through Day 11

• PK Profile for Naltrexone only: Cmax, AUC0-24, Tmax, and CL/F

  Descriptive statistics will be used to summarize naltrexone concentrations at each time point and PK parameters by treatment phase. Comparisons will be made between Day 10 and Day 11 for Cmax, AUC0-24, and Tmax at steady-state.

  Day 4 through Day 11

Secondary Outcomes (1)

• All Adverse Events (AEs) and Serious Adverse Events (SAEs) will be reported throughout the study and will include all subjects who receive at least 1 dose of study medication.

  Day 1 through 14

Study Arms (1)

Lofexidine + Naltrexone

EXPERIMENTAL

Drug: Lofexidine + Naltrexone

Interventions

Lofexidine + Naltrexone DRUG

Lofexidine HCl (two 0.2 mg tablets) will be administered as a single oral dose (0.4 mg) on Day 1 and on Day 11.Commercially available naltrexone HCL tablets will be administered as a single oral 25 mg dose on Day 4 and as a single oral 50 mg dose on Days 5 through 13. On Day 11 administration of both naltrexone and lofexidine will occur. Dose administration times for each drug are to be standardized for all treatment days. The scheduling of the naltrexone dose is to be standardized so that the naltrexone dose is administered 2 hours after the lofexidine dose on Day 11 when both drugs are administered.

Also known as: Lofexidine HCL, Naltrexone HCL

Lofexidine + Naltrexone

Eligibility Criteria

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

You may qualify if:

• BMI between 18 and 35 kg/m\^2
• females of childbearing potential must be using contraception or must be surgically sterile
• Subject is in good health based on medical history, physical exam, laboratory profile, electrocardiogram (ECG) as judged by investigator
• If subject smokes, subject agrees to limit smoking while in the study to not more than 10 cigarettes per day
• Subject provides written informed consent before participation in the study, and an appropriate HIPAA (Health Insurance Portability and Accountability Act) form is signed and dated

You may not qualify if:

• Subject has a history of clinically significant disease, including cardiovascular, gastrointestinal (GI), renal, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.
• Females: pregnant, breastfeeding, planning to become pregnant, or a positive pregnancy test.
• Clinically significant illness within 4 weeks before Day -1.
• Use of herbal supplements within 3 weeks before Day -1.
• Received treatment of more than a single dose of a CYP3A4 inducer (e.g., rifampin, barbiturates, phenytoin, glucocorticoids, St. John's Wort) within 4 weeks before Day -1.
• Received treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, diltiazem, macrolide antibiotics) within 2 weeks before Day -1.
• Currently taking any medication identified as potentially producing QTc prolongations of 10 msec or greater.
• Received an investigational medication during the last month (30 days) preceding 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.
• Consumed grapefruit, grapefruit juice, Seville oranges, and/or starfruit within 4 days before Day -1.
• Positive urine drug or alcohol screen, unless positive result is due to an approved prescribed medication (e.g., pain medication or benzodiazepine).
• Positive human immunodeficiency virus (HIV) test or tests positive for hepatitis B surface antigen.
• Known allergy or intolerance to any compound in the test product or any other closely related compound.
• Donated blood/plasma, exceeding 500 mL, during the 3-month period before Day -1.
• Abnormal cardiovascular exam at Screening, including any of the following: clinically significant abnormal ECG (e.g., second or third degree heart block, uncontrolled arrhythmia, QTcF \[Fridericia's correction\] interval \>450 msec for males and \>470 msec for females); pulse\<45 bpm or symptomatic bradycardia; systolic blood pressure \<90 mmHg or symptomatic hypotension; blood pressure \>165/95 mmHg; or prior history of myocardial infarction within 1 year before Day -1.

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; Naltrexone

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• George 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: May 7, 2015
• First Posted: May 15, 2015
• Study Start: May 1, 2015
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: October 26, 2017

Record last verified: 2017-10

Locations

US (1)