Clinical trial NCT00879645
Conditions: Renal Impairment
Keywords: Renal Impairment Renal Disease Sodium Sulfide
Sponsor: Mallinckrodt
Start date: 2009-08-01; Completion date: 2010-03-01
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase 1 study to assess the pharmacokinetics (PK) of IK-1001 (sodium sulfide) in healthy volunteers as well as in subjects with varying degrees of impaired renal function. A total of 28 subjects will be enrolled into the study over a 6 month period. There will be 4 cohorts. The first cohort will consist of subjects with mild renal impairment, the fourth cohort will be subjects with intermediate renal impairment and the third cohort will be subjects with severe renal impairment and the second cohort will consist of normal healthy subjects. All subjects will receive the study drug for 3 hours as a single intravenous (IV) infusion and will be followed over a 7 day period.

Detailed description:
This is a Phase 1 pharmacokinetic study to assess the pharmacokinetics of IK-1001 in healthy volunteers as well as subjects with varying degrees of impaired renal function following a single intravenous infusion.

A total of 28 subjects will be enrolled into the study, including 6 normal subjects (Creatinine Clearance (CrCL) \> 80 mL/min), 9 subjects with mild impairment (CrCL ≥ 50 to \< 80 mL/min), 6 subjects with intermediate impairment (≥ 30 to \< 50 mL/min) and 7 subjects with severe impairment (CrCL \< 30 mL/min).

Mild, moderate and normal healthy subjects will receive IK-1001 as a single IV infusion for 3 hours at 1.5 mg/kg/hr. Blood, plasma, urine and exhaled air will be collected from each subject over 48 hours and at follow-up visit (Day 7), to evaluate pharmacokinetics of Hydrogen Sulfide (H2S) (exhaled air), IK-1001 (blood) and thiosulfate in plasma and urine. Severe subjects will receive IK-1001 as a single IV infusion for 3 hours at 1.0 mg/kg/hr.

For each dosing cohort, the study will consist of a screening visit (Days -28 to -1), a treatment visit (Day 0 (check-in) to Day 3), and a follow-up (exit) visit day 7 (+/- 2 days).

Study subjects will be enrolled to one of 4 cohorts and all will receive investigational product at the given dose level. The subjects will be considered to be enrolled in the study at randomization.

IK-1001 will be administered by a healthcare professional intravenously over 3 hours using an infusion pump. Dosage of IK-1001 will be administered on actual body weight basis, according to cohort assignment and using the subject's body weight determined on Day -1. After the end of the initial 3-hour study period, subjects will be observed for an additional 45 hour period before discharge from the unit.

Arms: arm 1: Mild renal impairment (RI) Cohort administered 1.5 mg/kg/hr infusion of Sodium sulfide intravenously for 3 hours. arm 2: Healthy subjects received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours arm 3: Moderate RI cohort received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours arm 4: Severe RI cohort received sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours
Interventions: intervention 1: Sodium Sulfide intervention 2: Sodium Sulfide intervention 3: Sodium Sulfide intervention 4: Sodium Sulfide
Intervention descriptions: intervention 1: Sodium sulfide administered intravenously at 1.5 mg/kg/hr for 3 hours intervention 2: Sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours intervention 3: Sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours intervention 4: Sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours

Protocol documents: