Pharmacokinetic Assessment of Sodium Sulfide in Subjects With Impaired Renal Function

This study has been completed.
Sponsor:
Information provided by:
Ikaria
ClinicalTrials.gov Identifier:
NCT00879645
First received: April 9, 2009
Last updated: November 15, 2010
Last verified: November 2010

April 9, 2009
November 15, 2010
August 2009
March 2010   (final data collection date for primary outcome measure)
  • Thiosulfate in Plasma [ Time Frame: 8 hours after treatment ] [ Designated as safety issue: No ]
    Total concentration of thiosulfate in plasma was measured through pharmacokinetic blood sampling.
  • Thiosulfate in Urine [ Time Frame: 48 hours after treatment ] [ Designated as safety issue: No ]
    Total concentration of thiosulfate in urine was measure through pharmacokinetic urine collection
  • Sodium Sulfide in Blood [ Time Frame: 8 hours after treatment ] [ Designated as safety issue: No ]
    Total concentration of sodium sulfide in blood was measured through pharmacokinetic blood sampling.
  • Pharmacokinetics Urine Collection [ Time Frame: Baseline through day 3 ] [ Designated as safety issue: No ]
  • Pharmacokinetics Blood Sampling [ Time Frame: 30 minutes after infusion continued through day 7 ] [ Designated as safety issue: No ]
  • Exhaled Sulfide [ Time Frame: Baseline through day 2 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00879645 on ClinicalTrials.gov Archive Site
  • Vital Signs [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]
  • Urinalysis [ Time Frame: Baseline, Days 1, 2, and 7 ] [ Designated as safety issue: Yes ]
  • Hematology [ Time Frame: Baseline, Days 1 and 2 ] [ Designated as safety issue: Yes ]
  • 12-lead ECG [ Time Frame: Baseline, Day 0 through 7 ] [ Designated as safety issue: Yes ]
  • Coagulation Factors [ Time Frame: Baseline, Day 1, 2, and 7 ] [ Designated as safety issue: Yes ]
  • Biochemistry [ Time Frame: Baseline, Days 1, 2, and 7 ] [ Designated as safety issue: Yes ]
  • Creatinine Clearance [ Time Frame: Baseline, Day 7 ] [ Designated as safety issue: Yes ]
  • Exhaled Sulfide [ Time Frame: Baseline through day 2 ] [ Designated as safety issue: No ]
  • Vital Signs [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]
  • Urinalysis [ Time Frame: Baseline, Days 2, 3, and 7 ] [ Designated as safety issue: Yes ]
  • Hematology [ Time Frame: Baseline, Days 2 and 3 ] [ Designated as safety issue: Yes ]
  • 12-lead ECG [ Time Frame: Baseline, Day1 through 7 ] [ Designated as safety issue: Yes ]
  • Coagulation Factors [ Time Frame: Baseline, Day 2, 3 and 7 ] [ Designated as safety issue: Yes ]
  • Biochemistry [ Time Frame: Baseline, Days 2, 3, and 7 ] [ Designated as safety issue: Yes ]
  • Creatinine Clearance [ Time Frame: Baseline, Day 7 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Pharmacokinetic Assessment of Sodium Sulfide in Subjects With Impaired Renal Function
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

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Renal Impairment
  • Drug: Sodium Sulfide
    Sodium sulfide administered intravenously at 1.5 mg/kg/hr for 3 hours
    Other Name: IK-1001
  • Drug: Sodium Sulfide
    Sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
    Other Name: IK-1001
  • Drug: Sodium Sulfide
    Sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours
    Other Name: IK-1001
  • Experimental: Sodium Sulfide - Mild Cohort
    Mild renal impairment (RI) Cohort administered 1.5 mg/kg/hr infusion of Sodium sulfide intravenously for 3 hours.
    Intervention: Drug: Sodium Sulfide
  • Experimental: Sodium Sulfide - Healthy Cohort
    Healthy subjects received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
    Intervention: Drug: Sodium Sulfide
  • Experimental: Sodium Sulfide - Moderate Cohort
    Moderate RI cohort received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
    Intervention: Drug: Sodium Sulfide
  • Experimental: Sodium Sulfide - Severe Cohort
    Severe RI cohort received sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours
    Intervention: Drug: Sodium Sulfide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
March 2010
March 2010   (final data collection date for primary outcome measure)

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)
Both
18 Years to 70 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00879645
S103
Yes
Brahm Goldstein, MD, MCR, FAAP, FCCM, Ikaria
Ikaria
Not Provided
Study Director: Brahm Goldstein, MD Ikaria
Ikaria
November 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP