Pharmacokinetic & Pharmacodynamic Interaction of Lofexidine and Buprenorphine in Buprenorphine Maintained Patients

Completed · Phase 1 · Has a placebo group

Conditions studied: Opioid Dependence, Buprenorphine Withdrawal Syndrome

In brief

The primary objective of this study is to assess lofexidine related effects on QTc (an interval of the heart rhythm) in subjects receiving buprenorphine maintenance. The secondary objectives of the study are to evaluate the safety and tolerability of lofexidine by evaluating and monitoring pharmacokinetics (amounts of drug in the blood), vital signs (heart rate and blood pressure) and adverse events (side effects) when co-administered with buprenorphine; to describe effects on opiate withdrawal when lofexidine is introduced following a 50% buprenorphine dose reduction, as required to elicit a withdrawal response; and to evaluate QTc interaction effects of lofexidine compared with placebo. The Investigators hypothesize that while lofexidine is known to prolong the QTc interval, the combination of the drugs will not create an additive effect which creates a significant safety concern. The Investigators further hypothesize that subjects will be able to tolerate the therapeutic dose of lofexidine (0.8 mg four times daily) when the buprenorphine maintenance dose is lowered to elicit withdrawal.

Key facts

Study ID

NCT01820442

Run by

USWM, LLC (dba US WorldMeds)

People needed

30

Starts

2013-03-01

Expected to finish

2013-09-01

Last updated by the study team

2018-02-23

Who can join

Age: 18 and older, up to 60. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Adult male and/or female, 18 to 60 years of age (inclusive).
• Receiving buprenorphine maintenance treatment for opioid dependence at a stable total daily dose of 16-24 mg for at least 4 weeks prior to check-in for the Inpatient Treatment Visit.
• Body mass index ≥ 18 and ≤ 35 (kg/m2).
• Normal screening results or abnormal results that have been deemed by the Investigator as clinically insignificant.
• Able to understand and willing to sign an informed consent form (ICF).
• Females practicing adequate birth control or non-childbearing potential. Medically acceptable birth control methods for this study include intrauterine device (IUD); vasectomized partner (minimum of 6 months); post-menopausal (at least 2 years); surgically sterile (at least 6 months); double barrier (diaphragm with spermicide, condoms with vaginal spermicide); abstinence; implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive months prior to study dosing and throughout the study duration; and oral, patch and injected hormonal contraceptives or vaginal hormonal device (ie, NuvaRing®) in use for at least 3 consecutive months prior to study dosing and throughout the study duration.

You may not qualify if…

• Abnormal cardiovascular exam at screening and before randomization, including any of the following*:
• clinically significant abnormal electrocardiogram (ECG) (eg, significant first degree atrioventricular block, complete left bundle branch block [LBBB], second or third degree heart block, clinically significant arrhythmia, or QTcF interval (machine read) greater than 450 msec for males and greater than 470 msec for females)
• heart rate < 55 bpm or symptomatic bradycardia
• systolic blood pressure (SBP) < 95 mmHg or symptomatic hypotension
• diastolic blood pressure (DBP) < 65 mmHg
• blood pressure (BP) > 155/95 mmHg
• change in orthostatic SBP, DBP, or heart rate >25% below sitting values
• prior history of myocardial infarction (MI) or evidence of prior MI on ECG
• history of long QT syndrome or relative with this condition
• history of syncopal episodes
• intraventricular conduction delay with QRS duration >120 ms
• evidence of ventricular pre-excitation (eg, Wolff Parkinson White syndrome)
• ECGs and vitals may be repeated as appropriate in order to confirm values and rule out extraneous results.
• History or presence of significant or clinically unstable cardiovascular (including atrial fibrillation, congestive heart failure, myocardial ischemia, indwelling pacemaker), hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, psychiatric, neurologic, or dermatologic disease.
• History or presence of any degree of chronic obstructive pulmonary disease.
• History of suicidal ideations or depression requiring professional intervention including counseling or antidepressant medication over the past 12 months.
• Positive drug (urine)/alcohol (breath) test at screening or check-in excluding buprenorphine. Subjects who have a positive test for heroin, tetrahydrocannabinol (THC), and benzodiazepines at the Screening Visit may be enrolled if the test is negative at check-in to the Inpatient Treatment Visit. Subjects who have a positive test for heroin, THC or benzodiazepines at the Screening Visit must sign an ICF at check-in to the Inpatient Clinic Visit.
• Receiving buprenorphine for pain management.
• Positive test for human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg). Subjects with a positive test for hepatitis C antibodies (HCV) may be enrolled if subject is asymptomatic.
• Estimated creatinine clearance < 80 mL/minute at screening (Cockcroft-Gault formula).
• AST, ALT, or alkaline phosphatase > 3.0 x upper limit of normal at screening or check-in.
• Amylase or lipase > 1.5 x upper limit normal at screening or check-in.
• Clinically significant out-of-reference range clinical chemistry values, with particular attention to potassium, magnesium, and calcium.
• History of hypotension.
• History of hypersensitivity or allergy to clonidine or any clonidine analogue.

Where it is running

• Lifetree Clinical Research — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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