Clinical trial NCT00879645: Pharmacokinetic Assessment of Sodium Sulfide in Subjects With Impaired Renal Function
Official title: A Phase I Study to Assess the Pharmacokinetics of IK-1001 (Sodium Sulfide) in Subjects With Impaired Renal Function Following a Continuous 3-hour Intravenous Infusion
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Renal Impairment
Renal Disease
Sodium Sulfide
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2009-04-10
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. For normal subjects arm (CrCL \> 80 ml/min): Healthy male and female subjects age 18 to 70 years of age inclusive. Pregnant women are excluded and women of child-bearing potential must agree to the use of medically reliable contraceptive methods for the duration of the study and for 30 days after study.

   For renally impaired arm: Male and female - pregnant women are excluded and women of child-bearing potential must agree to the use of medically reliable contraceptive methods for the duration of the study and for 30 days after study. Subjects with mild, moderate and severe renal function aged between 18 to 70 years old
2. Body mass index (BMI) within the range of 18 to 40 kg/m2
3. Electrocardiogram (ECG) recording without clinically relevant abnormalities
4. Having had no febrile or infectious disease for at least seven days prior to dosing of study drug
5. Able to communicate well with the study staff and to understand and comply with the requirements of the study, understand and sign the written informed consent

Exclusion Criteria:

1. High risk patients who may need an urgent dialysis during clinical conduct portion of the study (from Day -1 until last PK sampling on Day 7)
2. All smokers.
3. More than moderate alcohol consumption (\>35 g ethanol regularly or \> 2 drinks per day )
4. Any history of alcohol or drug abuse
5. Any active physical or psychiatric disease, acute or chronic
6. Any clinically relevant history of drug hypersensitivity, asthma, urticaria or other severe allergic diathesis
7. Pregnant or nursing women
8. Blood donation within 30 days
9. Participation in any clinical study within 30 days prior to the treatment phase of this study
10. Lab values outside of reference range and clinically relevant liver function tests (AST, ALT, gamma-GT)
11. Positive tests for HIV antibodies, Hepatitis B-virus surface antigen (HBsAg), Anti-Hepatitis C-virus antibodies (Anti-HCV)

Primary outcomes:
measure: Thiosulfate in Plasma
timeFrame: 8 hours after treatment
measure: Thiosulfate in Urine
timeFrame: 48 hours after treatment
measure: Sodium Sulfide in Blood
timeFrame: 8 hours after treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
Study officials:
affiliation: Mallinckrodt
name: Brahm Goldstein, MD
role: STUDY_DIRECTOR
References: