Lofexidine ADME & Mass Balance in Volunteers

NCT01310296 | Completed Phase 1

• 1 other identifier: USWM-LX1-1003/ 02749MZ
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the mass balance and absolute bioavailability of a single oral dose of 14C-labeled lofexidine compared to a single intravenous dose of lofexidine.

Conditions

Normal Healthy Volunteers Will be Treated With Lofexidine to Understand the Absolute Bioavailability and Mass Balance Recovery of the Product

Keywords

Phase 1; Normal Healthy Volunteers; Mass Balance; ADME; Absolute Bioavailability

Outcome Measures

Primary Outcomes (1)

• Mass Balance

  To determine the mass balance recovery of orally administered lofexidine hydrochloride

  plasma, urine, and fecal samples up to 216 hours post dose

Secondary Outcomes (1)

• Absolute Bioavailability & Tolerability

  plasma samples over 72 and 144 hrs post-dose for IV and oral doses, respectively

Study Arms (2)

Radiolabeled Lofexidine Oral Solution

OTHER

Participants will receive a radiolabeled lofexidine oral solution followed by safety evaluations, and plasma, urine and fecal sampling for up to 216 hours post dose.

Drug: Lofexidine hydrochloride

Lofexidine Intravenous Solution

EXPERIMENTAL

Participants will receive 200 mcg of lofexidine in an intravenous solution infusion over 200 minutes followed by 72 hours of safety evaluation and plasma sampling.

Drug: Lofexidine hydrochloride

Interventions

Lofexidine hydrochloride DRUG

Single Dose = Solution containing 400 μg lofexidine HCl and a tracer amount of 14C lofexidine

Radiolabeled Lofexidine Oral Solution

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must be a male or non-pregnant, non-breastfeeding female.
• Subject must be between 18 and 50 years of age (inclusive).
• Subject's Body Mass Index (BMI) must be between 18 and 30 kg/m2 (inclusive), and subject must weigh a minimum of 50 kg (110 lbs).
• Female subjects must agree to use one of the following forms of birth control from screening until 14 days after completion of the study:
• Vasectomized partner (at least 6 months prior to dosing)
• Post-menopausal (at least 2 years prior to dosing)
• Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) at least 6 months prior to dosing
• Double barrier (diaphragm with spermicide; condoms with spermicide)
• IUD (intra-uterine device)
• Abstinence (must agree to use a double barrier method if they become sexually active during the study)
• Implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive months prior to study dosing and throughout the study duration
• Oral, patch, and injected contraceptives or vaginal hormonal device (i.e. NuvaRing®) in use for at least 3 consecutive months prior to study dosing and throughout the study duration.
• Subject must voluntarily consent to participate in this study and provide their written informed consent prior to start of any study- specific procedures.
• Subject is willing and able to remain in the study unit for the entire duration of each confinement period.
• Subject's vital signs must be within the following ranges to be included: Vital signs measured sitting after 3 minutes rest; heart rate: 50-90 bpm; systolic BP: 100-140 mmHg; diastolic BP: 50-90 mmHg, and oral temperature within the normal range of 35.6-37.7° C. Out-of-range vital signs may be repeated once. Predose vital signs will be assessed by the Principal Investigator or designee (e.g., a medically qualified sub-investigator) prior to study drug administration. The Principal Investigator or designee will verify the eligibility of each subject with out-of-range vital signs and document approval prior to dosing.

You may not qualify if:

• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
• Has a clinically significant abnormal finding on the physical exam, medical history, ECG, or clinical laboratory results at screening.
• History of any syncopal episode or seizures.
• Presence of acute disease state (eg, nausea, vomiting, fever, diarrhea) within 7 days prior to scheduled dose administration.
• History or presence of allergic or adverse response to lofexidine or related drugs.
• Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication.
• Has donated blood or plasma within 30 days prior to the first dose of study medication.
• Has participated in a radiolabeled clinical trial within the last 12 months prior to the first dose of study medication.
• Has participated in another clinical trial (randomized subjects only) within 30 days prior to the first dose of study medication.
• Has used any over-the-counter (OTC) medication, including nutritional supplements, within 7 days prior to the first dose of study medication.
• Has used any prescription medication, except hormonal contraceptive or hormonal replacement therapy, within 14 days prior to the first dose of study medication.
• Subjects that have discontinued the use of implanted, intrauterine, or injected hormonal contraceptives must not have used any for 6 months prior to study start.
• Subjects that have discontinued the use of oral, patch, or vaginal hormonal contraceptives must not have used any for 1 month prior to study start.
• Has been treated with any known drugs that are moderate or strong inhibitors/inducers of CYP enzymes such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication and that in the Investigator's judgment may impact subject safety or the validity of the study results.
• Has smoked or used tobacco products within 60 days prior to the first dose of study medication.

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

Study Officials

• James A Longstreth, PhD

  US WorldMeds

  PRINCIPAL INVESTIGATOR

• Charles W Gorodetzky, MD, PhD

  US WorldMeds

  PRINCIPAL INVESTIGATOR

• Mark Leibowitz, MD

  Worldwide Clinical Trials

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2011
• First Posted: March 8, 2011
• Study Start: July 1, 2011
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: October 26, 2017

Record last verified: 2017-10

Locations

US (1)