Single-dose Pharmacokinetics and Safety of Oral Lofexidine in Renally-Impaired Subjects
Condition: Renally Impaired Subjects
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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 (creatinine [Cr] clearance >90 mL/min), recruited as 1:1 matches to
      each ESRD subject, matched for gender, age (±10 years), and body mass index (BMI) (±15%).
      Normal renal function and ESRD subjects will be confined to an inpatient facility from the
      day before dosing to 144 or 156 hours after dosing, respectively, for a total of 7 8 nights
      and 8-9 days of inpatient confinement.

      Subjects who successfully complete screening will report to the inpatient facility at an
      appropriate time the day before study drug administration to undergo pre-dosing study
      procedures (Day 1). The next morning (Day 1), all subjects will receive breakfast
      (approximately 6 hours before planned lofexidine dosing) and then ESRD subjects will begin
      their hemodialysis session. All subjects will receive a single, oral dose of 400 µg
      lofexidine HCl (two 200 µg tablets), dosed with 240 mL of water, the clock time for which
      will be approximately the same for both normal renal function subjects and ESRD subjects.
      Because ESRD subjects will be maintained on 3 times per week dialysis, lofexidine will be
      administered near the beginning of a 3-day between-dialysis interval.

      Fingerprick blood samples for subjects with normal renal function will be collected for PK
      analysis at multiple time points over the next 144 hours. Fingerprick blood samples for ESRD
      subjects will be collected for PK analysis at multiple time points over the next 156 hours.
      Fingerprick blood samples (0.5 mL each) will be collected in BD Microtainer pink top K2EDTA
      tubes.

      Two (2) venous blood samples (4-6 mL each in K2EDTA tubes) will be collected from each
      subject for lofexidine protein binding analysis, one sample collected 0-60 minutes before
      dosing and one sample collected 4 hours post-dose.

      Pooled urine samples for subjects with normal renal function will be collected at 0 3 hours,
      3 6 hours, 6 12 hours, 12 24 hours, 24 48 hours, 48 72 hours, 72 96 hours, and 96 144 hours
      post-dose. Pooled urine samples will be collected from ESRD subjects as available according
      to the same schedule.

      Arterial and venous blood samples from the arterial-venous (A-V) shunt (0.5 mL in BD
      Microtainer pink top K2EDTA tubes) for PK analysis will be collected from ESRD subjects at
      0.5, 1.5, 2.5, and 3.5 hours into each of the two 4 hour hemodialysis sessions. Additionally,
      fingerprick blood samples (0.5 mL) will be collected from the hand contralateral to the arm
      used for the dialysis A V shunt at each of these specified time points. Dialysate from ESRD
      subjects will be collected during the two 4 hour hemodialysis sessions at 0 1 hour, 1 2 hour,
      2 3 hour, and 3 4 hour. Two 10 mL samples from each of the 1-hour pooled dialysate
      collections will be aliquoted into suitable collection tubes.

      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
      physical exams.
    

Intervention name(s): lofexidine HCl
Intervention type(s): Drug
Intervention description(s): 400 micrograms
Intervention MeSH terms: Lofexidine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: ESRD; End Stage Renal Disease; Normal Healthy Volunteers; Renally Impaired