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Pharmacokinetic Assessment of Sodium Sulfide in Subjects With Impaired Renal Function

Primary Purpose

Renal Impairment

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Sodium Sulfide

About this trial

This is an interventional treatment trial for Renal Impairment focused on measuring Renal Impairment, Renal Disease, Sodium Sulfide

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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
Body mass index (BMI) within the range of 18 to 40 kg/m2
Electrocardiogram (ECG) recording without clinically relevant abnormalities
Having had no febrile or infectious disease for at least seven days prior to dosing of study drug
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:

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)
All smokers.
More than moderate alcohol consumption (>35 g ethanol regularly or > 2 drinks per day )
Any history of alcohol or drug abuse
Any active physical or psychiatric disease, acute or chronic
Any clinically relevant history of drug hypersensitivity, asthma, urticaria or other severe allergic diathesis
Pregnant or nursing women
Blood donation within 30 days
Participation in any clinical study within 30 days prior to the treatment phase of this study
Lab values outside of reference range and clinically relevant liver function tests (AST, ALT, gamma-GT)
Positive tests for HIV antibodies, Hepatitis B-virus surface antigen (HBsAg), Anti-Hepatitis C-virus antibodies (Anti-HCV)

Sites / Locations

DaVita Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Sodium Sulfide - Mild Cohort

Sodium Sulfide - Healthy Cohort

Sodium Sulfide - Moderate Cohort

Sodium Sulfide - Severe Cohort

Arm Description

Mild renal impairment (RI) Cohort administered 1.5 mg/kg/hr infusion of Sodium sulfide intravenously for 3 hours.

Healthy subjects received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours

Moderate RI cohort received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours

Severe RI cohort received sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours

Outcomes

Primary Outcome Measures

Thiosulfate in Plasma

Total concentration of thiosulfate in plasma was measured through pharmacokinetic blood sampling.

Thiosulfate in Urine

Total concentration of thiosulfate in urine was measure through pharmacokinetic urine collection

Sodium Sulfide in Blood

Total concentration of sodium sulfide in blood was measured through pharmacokinetic blood sampling.

Secondary Outcome Measures

Full Information

NCT ID

NCT00879645

First Posted

April 9, 2009

Last Updated

December 13, 2019

Sponsor

Mallinckrodt

1. Study Identification

Unique Protocol Identification Number

NCT00879645

Brief Title

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

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Terminated

Why Stopped

unable to develop a rapid & reliable assay to detect sulfide concentrations

Study Start Date

August 2009 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mallinckrodt

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Impairment

Keywords

Renal Impairment, Renal Disease, Sodium Sulfide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sodium Sulfide - Mild Cohort

Arm Type

Experimental

Arm Description

Mild renal impairment (RI) Cohort administered 1.5 mg/kg/hr infusion of Sodium sulfide intravenously for 3 hours.

Arm Title

Sodium Sulfide - Healthy Cohort

Arm Type

Experimental

Arm Description

Healthy subjects received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours

Arm Title

Sodium Sulfide - Moderate Cohort

Arm Type

Experimental

Arm Description

Moderate RI cohort received sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours

Arm Title

Sodium Sulfide - Severe Cohort

Arm Type

Experimental

Arm Description

Severe RI cohort received sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours

Intervention Type

Drug

Intervention Name(s)

Sodium Sulfide

Other Intervention Name(s)

IK-1001

Intervention Description

Sodium sulfide administered intravenously at 1.5 mg/kg/hr for 3 hours

Intervention Type

Drug

Intervention Name(s)

Sodium Sulfide

Other Intervention Name(s)

IK-1001

Intervention Description

Sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours

Intervention Type

Drug

Intervention Name(s)

Sodium Sulfide

Other Intervention Name(s)

IK-1001

Intervention Description

Sodium sulfide intravenously at 1.5 mg/kg/hr for 3 hours

Intervention Type

Drug

Intervention Name(s)

Sodium Sulfide

Other Intervention Name(s)

IK-1001

Intervention Description

Sodium sulfide intravenously at 1.0 mg/kg/hr for 3 hours

Primary Outcome Measure Information:

Title

Thiosulfate in Plasma

Description

Total concentration of thiosulfate in plasma was measured through pharmacokinetic blood sampling.

Time Frame

8 hours after treatment

Title

Thiosulfate in Urine

Description

Total concentration of thiosulfate in urine was measure through pharmacokinetic urine collection

Time Frame

48 hours after treatment

Title

Sodium Sulfide in Blood

Description

Total concentration of sodium sulfide in blood was measured through pharmacokinetic blood sampling.

Time Frame

8 hours after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Body mass index (BMI) within the range of 18 to 40 kg/m2 Electrocardiogram (ECG) recording without clinically relevant abnormalities Having had no febrile or infectious disease for at least seven days prior to dosing of study drug 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: 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) All smokers. More than moderate alcohol consumption (>35 g ethanol regularly or > 2 drinks per day ) Any history of alcohol or drug abuse Any active physical or psychiatric disease, acute or chronic Any clinically relevant history of drug hypersensitivity, asthma, urticaria or other severe allergic diathesis Pregnant or nursing women Blood donation within 30 days Participation in any clinical study within 30 days prior to the treatment phase of this study Lab values outside of reference range and clinically relevant liver function tests (AST, ALT, gamma-GT) Positive tests for HIV antibodies, Hepatitis B-virus surface antigen (HBsAg), Anti-Hepatitis C-virus antibodies (Anti-HCV)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Brahm Goldstein, MD

Organizational Affiliation

Mallinckrodt

Official's Role

Study Director

Facility Information:

Facility Name

DaVita Clinical Research

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55404

Country

United States

12. IPD Sharing Statement

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Pharmacokinetic Assessment of Sodium Sulfide in Subjects With Impaired Renal Function

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