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

Completed · Phase 1

Conditions studied: Renally Impaired Subjects

In brief

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.

Key facts

Study ID

NCT02313103

Run by

USWM, LLC (dba US WorldMeds)

People needed

16

Starts

2014-11-01

Expected to finish

2015-02-01

Last updated by the study team

2017-10-26

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Study site — Orlando, Florida, United States

Full record on ClinicalTrials.gov

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