A Phase 1, open-label, single-arm study with two single doses of lofexidine and multiple
doses of naltrexone in healthy adult subjects to determine the effect of naltrexone on the
single dose pharmacokinetics of the oral lofexidine formulation.
Subjects will be confined to an inpatient facility for a total of 14 nights and 15 days.
Subjects who successfully complete screening will report to the inpatient facility (Day -1).
At Day 1 all subjects will receive the first single, oral dose of 0.4 mg lofexidine HCl (two
0.2 mg tablets) dosed with 240 mL of water (no food). The lofexidine dose will be followed by
a 74-hour interval before beginning naltrexone daily dosing on Day 4 .The first naltrexone
administration on Day 4 will be at a dose of approximately 25 mg QD, with subsequent doses on
Days 5 to 13 at 50 mg QD. On Day 11, the second single dose of lofexidine (0.4 mg) will be
administered and followed by the daily administration of the naltrexone dose (50 mg). The
daily administration of naltrexone dose (50 mg) will continue on Day 12 and Day 13.After each
administration of lofexidine on Day 1 and Day 11, fingerstick blood samples will be collected
for lofexidine pharmacokinetic (PK) analysis before dosing and after dosing at multiple time
points.Safety will be assessed by recording adverse events (AEs), measuring vital signs
(blood pressure and pulse rate) and clinical laboratory tests (chemistry, hematology, and
urinalysis), recording 12-lead safety and Holter electrocardiograms (ECGs), and performing
- BMI between 18 and 35 kg/m^2
- females of childbearing potential must be using contraception or must be surgically
- 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
- 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
- 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
- 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
- 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
- Known allergy or intolerance to any compound in the test product or any other closely
- 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.