Efficacy, Safety and Dose-Response Study Followed by Open-Label Study of Lofexidine Treatment of Opioid Withdrawal
Condition: Opioid Dependence; Acute Opioid Withdrawal Syndrome
MeSH terms: Opioid-Related Disorders; Substance Withdrawal Syndrome
Intervention: Lofexidine HCl; Placebo; Open Label Lofexidine HCL
Intervention description: Lofexidine HCl tablets will be available in 0.2 mg tablets. Lofexidine will be provided in total daily doses as indicated during the double blind portion of the study.; Lofexidine-matching tablets without the active pharmaceutical ingredient will be provided as 4 tablets QID during the double-blind portion of the study to subjects randomized to placebo.; Lofexidine HCl tablets will are available in 0.2 mg tablets. During the optional open-label portion of the study, Lofexidine HCl can be prescribed at the discretion of the Investigator but total daily dose will not exceed 3.2 mg.
Intervention MeSH terms: Lofexidine; Clonidine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 603.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lofexidine; opioid dependence; acute withdrawal syndrome; opioid withdrawal

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.
    

Eligibility 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.