Open-Label, Safety Study of Lofexidine
Condition: Opioid Withdrawal
MeSH terms: Substance Withdrawal Syndrome
Intervention: Lofexidine
Intervention description: All enrolled subjects will take lofexidine orally for 7 days, starting on Day 1 at a dose of 3.2 mg per day (0.8 mg QID), with lowering of the dose allowed to 2.4 mg daily (0.6 mg QID) if required for tolerability based on the subject's individual treatment goal and response per clinical judgment of the Principal Investigator.
Intervention MeSH terms: Lofexidine; Clonidine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 286.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: detoxification; agonist taper; methadone step down; buprenorphine step down; opioid withdrawal syndrome

Summary:

      The purpose of this Phase 3 open-label treatment study is to evaluate the safety and
      effectiveness of lofexidine at a clinically relevant dose to alleviate symptoms of acute
      withdrawal from any opioid, including methadone and buprenorphine. This study will take place
      in a variety of clinical scenarios, both in-clinic and outpatient settings.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or Female at least 18 years of age

          -  Must be able to verbalize understanding of the consent form, able to provide written
             informed consent, and verbalize willingness to complete study procedures

          -  Must have current dependence, according to the Mini International Neuropsychiatric
             Interview (M.I.N.I.), on any opioid (including methadone and buprenorphine maintenance
             treatment)

          -  Must be seeking treatment for partial or total withdrawal from current opioid and
             expected, as determined by the Principal Investigator, to benefit from lofexidine
             treatment for at least 7 days at clinically relevant doses. This can include a variety
             of clinical situations where opioid withdrawal illness is likely to occur including
             abrupt and total withdrawal (including from methadone and buprenorphine),
             agonist-assisted total withdrawal, dose reduction of maintenance treatment (e.g.,
             methadone, buprenorphine) and transition from an opioid agonist to naltrexone or
             buprenorphine maintenance

          -  Must have Urine toxicology screen result of positive for opioid(s) relevant to the
             subject's withdrawal treatment goal

          -  If female and of childbearing potential, subject must agree to use of one of the
             following methods of birth control including oral contraceptives, patch, barrier
             (diaphragm, sponge or condom) plus spermicidal preparations, intrauterine
             contraceptive system, levonorgestrel implant, medroxyprogesterone acetate
             contraceptive injection, complete abstinence from sexual intercourse, hormonal vaginal
             contraceptive ring or surgical sterilization or partner sterile (with documented
             proof)

        Exclusion Criteria:

          -  Female subject who is pregnant or lactating

          -  History of very serious medical illness not under control including, but not limited
             to, active 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 and/or having an unstable psychiatric condition.
             These conditions will be determined at Screening by medical history, physical
             examination, 12 lead electrocardiogram (duplicate), clinical laboratory tests for
             infectious diseases, and a tuberculin test

          -  Current dependence (based on the M.I.N.I.) on any psychoactive substance (excluding
             caffeine, nicotine, and the subject's current opioid-dependence agent, which can
             include methadone and buprenorphine, for example, in agonist-maintained subjects) that
             requires detoxification or dose reduction as part of the pre-defined individual
             subject withdrawal treatment goal

          -  Have participated in an investigational drug study within the past 30 days

          -  Have a history of lofexidine exposure in a prior clinical trial or otherwise

          -  Have an abnormal cardiovascular exam at screening

          -  Any subject that requires tricyclic antidepressants, which may reduce the efficacy of
             imidazoline derivatives and/or beta-receptor blockers, to avoid the risk of excessive
             bradycardia