Study to Assess Pegloticase (KRYSTEXXA®) in Patients on Hemodialysis

A Phase 1, Single Site, Open-Label Study to Assess the Pharmacokinetics (PK) and Pharmacodynamics (PD) of Pegloticase (KRYSTEXXA®) in Patients on Hemodialysis

This is a Phase 1 single dose study conducted to evaluate the PK and PD of pegloticase administered to hemodialysis patients.

A single dose of pegloticase will be administered intravenously to male or female hemodialysis patients (N = 12) starting 3 hour prior to dialysis.

The study consists of a Screening Period, a Treatment Period, and Follow up Period.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease Stage 5
• Intervention / Treatment: Drug: Pegloticase

Detailed Description

End stage renal disease (ESRD) patients that require hemodialysis typically undergo hemodialysis treatment 3 times per week. As such, medications can be dialyzed off, reducing their clinical effectiveness; this study is being conducted to understand how dialysis affects the pharmacokinetics (PK) and pharmacodynamics (PD) of pegloticase.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Davita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 and 75 years of age, inclusive
2. Agrees to employ best possible methods to abstain from becoming pregnant or impregnating another.
3. Stage V chronic kidney patients with minimal or no residual renal function receiving hemodialysis and stable on hemodialysis (3x week)
4. BMI = 18.5 kg/m2 to < 45 kg/m2

Exclusion Criteria:

1. Any surgical or medical condition that may interfere with drug absorption, distribution, metabolism, or excretion, or any other condition that may place the subject at risk

   1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
   2. Uncontrolled congestive heart failure
   3. Refractory chronic gout
2. History of drug and/or alcohol abuse within 6 months prior to screening
3. History of or current clinically significant mental disorder or an antagonistic personality that compromises the validity of the informed consent
4. Donation of blood or plasma within 30 days prior to dosing
5. History of or current hepatitis, or carriers of hepatitis B surface antigen (HbsAg) and/or hepatitis C antibodies (anti-HC).
6. Use of an investigational drug or product, within 30 days
7. History of clinically significant drug allergies or sensitivities
8. Females with a positive pregnancy test or who are breast feeding at Screening or plan to breast feed within 30 days of dosing
9. A baseline QTc interval ≥ 490 milliseconds for males and ≥ 510 milliseconds for females
10. Is unable to refrain from alcohol
11. Has taken any prescription or over the counter medication within 7 days prior to treatment day that, in the opinion of the Investigator, could be expected to confound the PK or metabolism of the study drug
12. Has taken the following herbal agents or nutraceuticals within 7 days prior to Screening: chapparal, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's Wort, or valerian
13. Has poorly controlled malignant hypertension (systolic blood pressure [SBP] > 200 mm Hg and/or diastolic blood pressure [DBP] > 120 mm Hg,
14. Concurrent use of urate-lowering drugs

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegloticase; Pegloticase 8 mg single intraveneous dose	Drug: Pegloticase; a single 8 mg iv (in the vein) dose before hemodialysis session; Other Names: KRYSTEXXA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• To evaluate the pharmacokinetics (PK) of pegloticase after a single-dose administration to hemodialysis patients when administered starting 3 hours before dialysis	1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
• To evaluate the pharmacodynamics (PD) of pegloticase and SUA, before and after hemodialysis sessions	1 month

Collaborators and Investigators

• Sponsor: Savient Pharmaceuticals
• Investigators: Principal Investigator: Harry Alcorn, Pharm D, Davita Clinical Research

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: November 29, 2012
• First Submitted That Met QC Criteria: November 30, 2012
• First Posted (Estimate): December 3, 2012

Study Record Updates

• Last Update Posted (Estimate): October 25, 2013
• Last Update Submitted That Met QC Criteria: October 24, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Hemodialysis; Chronic Kidney Disease Stage 5; pegloticase
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: M0403; 10122 (Other Identifier: IND number)