Efficacy, Safety and Dose-Response Study Followed by Open-Label Study of Lofexidine Treatment of Opioid Withdrawal

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to look at the efficacy and safety for lofexidine hydrochloride, an alpha-2 adrenergic agonist under development for the treatment of acute withdrawal from short-acting opioids. The study takes place in 2 parts: a 7-day inpatient double-blind treatment portion where subjects will be randomly assigned to one of three doses of study medication (2.4 mg total daily dose of lofexidine, 3.2 mg total daily dose of lofexidine, or placebo) followed by an optional open-label treatment period where subjects will be inpatient or outpatient and receive lofexidine at variable dosing for up to an additional 7 days. The Investigator hypothesizes that subjects will achieve maximum treatment effect with tolerable side effects at the 3.2 mg total daily dose and that both the 3.2 mg and 2.4 total daily doses will show better efficacy over placebo in treating symptoms of acute opioid withdrawal.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: US WorldMeds LLC
• Collaborator: National Institute on Drug Abuse (NIDA)
• Treatments: Analgesics, Opioid; Clonidine; Lofexidine

Criteria

Inclusion Criteria:

• Male or female at least 18 years of age.

• Currently dependence, according to the Mini International Neuropsychiatric Interview (M.I.N.I.) [17, 18], on any opioid with a half-life similar to heroin or morphine, including Vicodin®, Lortab®, Lorcet®, Percocet®, Percodan®, Tylox®, or Hydrocodone (by any route of administration), or oxycodone (oxycodone and oxycodone time-released formulation when crushed and snorted, injected or swallowed after chewing).

• Seeking treatment for opioid dependence.

• Score of ≥2 on the Objective Opiate Withdrawal Scale (OOWS-Handelsman) at Baseline.

• Reported use of heroin, morphine, or any opioid with a half-life similar to heroin or morphine for at least 21 of the past 30 days.

• Urine toxicology screen positive for opioids but negative for methadone and buprenorphine.

• Females of childbearing potential must agree to using birth control methods and must have had documented proof.

• Able to verbalize understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, and pass the study consent quiz with 100% accuracy (if necessary, quiz may be administered more than one time).

Exclusion Criteria:

• Female subject who is pregnant or lactating.

• Self-reported use of methadone or buprenorphine in the past 14 days.

• Serious medical illnesses including, but not limited to: seizures, pancreatic disease, liver disease, exposure to a hepatitis virus, and positive hepatitis results.

• Psychiatric disorder, based on the M.I.N.I., including but not limited to dementia or any disorder that, in the opinion of the study physician requires ongoing treatment that would make study participation unsafe or which would make treatment compliance difficult.

• Self-reported acquired immune deficiency syndrome (AIDS) or self-reported human immunodeficiency virus (HIV) positive status and taking retroviral medications currently or within the past 4 weeks.

• Abnormal cardiovascular exam at screening and before randomization, including any of the following: clinically significant abnormal electrocardiogram (ECG) (e.g., second or third degree heart block, uncontrolled arrhythmia, or QTcF interval greater than 450 msec for males and greater than 470 msec for females); heart rate less than 55 bpm or symptomatic bradycardia; systolic blood pressure (SBP) less than 95 mmHg or symptomatic hypotension; diastolic blood pressure (DBP) less than 65 mmHg; blood pressure (BP) greater than 155/95 mmHg; and prior history of myocardial infarction.

• Clinically significant abnormal laboratory values.

• Requiring any of the following medications currently or within the past 4 weeks:

psychotropics (including sedatives/hypnotics, antidepressants, neuroleptics), prescription analgesics (excluding those listed in inclusion criterion #2 above), anticonvulsants, antihypertensives, antiarrhythmics, antiretroviral, and cholesterol lowering medications. Nicotine replacement therapy (patch, inhaler, gum, or nasal spray) will be allowed for nicotine-dependent subjects. Note: Use of a short-acting benzodiazepine (e.g., oxazepam) for insomnia during Days 8 14 will not disqualify a subject.

• Currently dependent (based on the M.I.N.I.) on any psychoactive substance (other than that listed in inclusion criterion #2, caffeine or nicotine) that requires detoxification.

• Donated blood within the last 8 weeks.

• Participated in an investigational drug study within the past 3 months.

• Has "poor" veins that even a single venipuncture cannot be obtained during screening.

• Active tuberculosis (positive tuberculin test and/or confirmatory diagnostic chest x-ray).

• Active syphilis.