Single-dose Pharmacokinetics and Safety of Oral Lofexidine in Renally-Impaired Subjects

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase 1, open-label, parallel-group, single-dose study of lofexidine in 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function, recruited as 1:1 matches to each ESRD subjects, matched for gender, age, and BMI.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

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

Criteria

Inclusion Criteria:

• Between ages of 18-75 years at enrollment with a BMI between 18 and 38 kg/m2, inclusive. Subjects with normal renal function: gender, age (±10 years), and BMI (±15%) matched to their ESRD subject.

• Male or female; however, if female: must be using contraception if of childbearing potential or must be surgically sterile; and must not be lactating.

• Subjects with ESRD must have been receiving adequate maintenance hemodialysis (at least 3 times per week) for at least 3 months before Day -1 (i.e., approximate Kt/V >1.1 based on subject's nephrologist and Investigator); subjects with normal renal function must have a creatinine clearance (CLcr) of less than or equal to 90 mL/min as estimated by Cockcroft and Gault or, if clinically indicated, by a 24 hour urine CLcr test.

• Subjects with ESRD must be on a stable medication program, except for medications prescribed for maintenance of hemoglobin, for at least 2 weeks before Day 1.

• At screening a matched control subject is in good health based on medical history, physical exam, laboratory profile, and ECG as judged by the Investigator.

• If subject smokes, subject agrees to limit smoking while in the study to not more than 10 cigarettes per day.

• 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:

• Fails to meet all of the inclusion criteria.

• The matched control subject has a history of clinically significant disease, including cardiovascular, gastrointestinal (GI), renal, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease or the ESRD subject has a history of clinically significant disease including cardiovascular, GI, 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 other than renal disease or known conditions associated with renal disease for ESRD subjects, 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 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, macrolides 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 or grapefruit juice within 4 days before Day 1.

• Positive urine or saliva (ESRD subjects) drug screen and alcohol breathalyzer test, unless positive result is due to an approved prescribed medication (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 electrolyte values, including any including any pre-dialysis values in ESRD subjects outside of the following ranges: potassium 3.0-6.5 mmol/L; calcium 7.0-11.0 mg/dL; sodium: 120 150 mmol/L.

• Abnormal cardiovascular exam at Screening, including any of the following: clinically significant abnormal ECG at Screening (e.g., second or third degree heart block, uncontrolled arrhythmia, QTcF [Fridericia's correction] interval >450 msec for males and >470 msec for females); heart rate <45 bpm or symptomatic bradycardia; systolic blood pressure <90 mmHg or symptomatic hypotension; blood pressure >180/105 mmHg; or prior history of myocardial infarction within 1 year before Day 1.

• Subjects with normal renal function will not be eligible to participate in the study if any of the following exclusion criteria also apply: Received any over-the-counter medication, including topical medications, vitamins, and nutritional supplements or any prescription medication (except female hormonal contraceptives or hormone replacement therapy) within 14 days or 5 half lives (whichever is less) before Day 1.

• Subjects with ESRD will not be eligible to participate in the study if any of the following exclusion criteria also apply: Recipient of a functioning transplanted solid organ.