Assessment of the Effect of Naltrexone on Lofexidine Single Dose Pharmacokinetics in Healthy Subjects

Inclusion Criteria:

• BMI between 18 and 35 kg/m^2
• females of childbearing potential must be using contraception or must be surgically sterile
• Subject is in good health based on medical history, physical exam, laboratory profile, electrocardiogram (ECG) as judged by investigator
• If subject smokes, subject agrees to limit smoking while in the study to not more than 10 cigarettes per day
• Subject provides written informed consent before participation in the study, and an appropriate HIPAA (Health Insurance Portability and Accountability Act) form is signed and dated

Exclusion Criteria:

• Subject has a history of clinically significant disease, including cardiovascular, gastrointestinal (GI), renal, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.
• Females: pregnant, breastfeeding, planning to become pregnant, or a positive pregnancy test.
• Clinically significant illness within 4 weeks before Day -1.
• Use of herbal supplements within 3 weeks before Day -1.
• Received treatment of more than a single dose of a CYP3A4 inducer (e.g., rifampin, barbiturates, phenytoin, glucocorticoids, St. John's Wort) within 4 weeks before Day -1.
• Received treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, diltiazem, macrolide antibiotics) within 2 weeks before Day -1.
• Currently taking any medication identified as potentially producing QTc prolongations of 10 msec or greater.
• Received an investigational medication during the last month (30 days) preceding Day -1.
• Consumes more than 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) or has a significant history of alcohol abuse or drug/chemical abuse within the last 1 year.
• Consumed grapefruit, grapefruit juice, Seville oranges, and/or starfruit within 4 days before Day -1.
• Positive urine drug or alcohol screen, unless positive result is due to an approved prescribed medication (e.g., pain medication or benzodiazepine).
• Positive human immunodeficiency virus (HIV) test or tests positive for hepatitis B surface antigen.
• Known allergy or intolerance to any compound in the test product or any other closely related compound.
• Donated blood/plasma, exceeding 500 mL, during the 3-month period before Day -1.
• Abnormal cardiovascular exam at Screening, including any of the following: clinically significant abnormal ECG (e.g., second or third degree heart block, uncontrolled arrhythmia, QTcF [Fridericia's correction] interval >450 msec for males and >470 msec for females); pulse<45 bpm or symptomatic bradycardia; systolic blood pressure <90 mmHg or symptomatic hypotension; blood pressure >165/95 mmHg; or prior history of myocardial infarction within 1 year before Day -1.