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Pharmacokinetic Assessment of Sodium Sulfide in Subjects With Impaired Renal Function

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

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.


Condition Intervention Phase
Renal Impairment
 Drug: Sodium Sulfide
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Ikaria Holdings Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 28
Study Start Date: August 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sodium Sulfide - Mild Cohort
Mild renal impairment (RI) Cohort administered 1.5 mg/kg/hr infusion of Sodium sulfide intravenously for 3 hours.
 Drug: Sodium Sulfide
Sodium sulfide administered intravenously at 1.5 mg/kg/hr for 3 hours
Other Name: IK-1001
Experimental: Sodium Sulfide - Healthy Cohort
Healthy subjects received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
 Drug: Sodium Sulfide
Sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
Other Name: IK-1001
Experimental: Sodium Sulfide - Moderate Cohort
Moderate RI cohort received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
 Drug: Sodium Sulfide
Sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours
Other Name: IK-1001
Experimental: Sodium Sulfide - Severe Cohort
Severe RI cohort received sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours
 Drug: Sodium Sulfide
Sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours
Other Name: IK-1001

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00879645

Locations
United States, Minnesota
DaVita Clinical Research
Minneapolis, Minnesota, United States, 55404
Sponsors and Collaborators
Ikaria Holdings Inc.
Investigators
Study Director: Brahm Goldstein, MD Ikaria Holdings Inc.
  More Information

No publications provided

Responsible Party: Brahm Goldstein, MD, MCR, FAAP, FCCM, Ikaria
ClinicalTrials.gov Identifier: NCT00879645     History of Changes
Other Study ID Numbers: S103
Study First Received: April 9, 2009
Results First Received: October 7, 2010
Last Updated: November 15, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Ikaria Holdings Inc.:
Renal Impairment
Renal Disease
Sodium Sulfide

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on May 16, 2013