Status:
COMPLETED
Pharmacokinetic & Pharmacodynamic Interaction of Lofexidine and Buprenorphine in Buprenorphine Maintained Patients
Lead Sponsor:
USWM, LLC (dba US WorldMeds)
Collaborating Sponsors:
National Institute on Drug Abuse (NIDA)
Conditions:
Opioid Dependence
Buprenorphine Withdrawal Syndrome
Eligibility:
All Genders
18-60 years
Phase:
PHASE1
Brief Summary
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 st...
Detailed Description
This will be a randomized, double-blind, placebo-controlled multiple ascending dose study to assess the safety, tolerability, and electrocardiographic effects of lofexidine in 30 buprenorphine-maintai...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- 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.
- Use of any new prescription medication within 12 days prior to check-in.
- Use of any over-the-counter medication, including herbal products, within the 5 days prior to check-in. Up to 3200 mg per day of ibuprofen or up to 2 grams per day of acetaminophen is allowed at the discretion of the principal investigator or his designee.
- Use of any drug known to affect QTc within 30 days prior to check-in (tobacco and buprenorphine excluded).
- Blood donation or significant blood loss within 30 days prior to check-in.
- Plasma donation within 7 days prior to check-in.
- Participation in another clinical trial within 30 days prior to check-in.
- Females who are pregnant or lactating.
- Participation in a prior study of lofexidine hydrochloride.
- Any other condition or prior therapy, which, in the opinion of the Investigator, would make the subject unsuitable for this study.
Key Trial Info
Start Date :
March 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
September 1 2013
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT01820442
Start Date
March 1 2013
End Date
September 1 2013
Last Update
February 23 2018
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Lifetree Clinical Research
Salt Lake City, Utah, United States, 84106