Evaluation of Patiromer Titration in Heart Failure Patients With Chronic Kidney Disease

Heart Failure Clinical Trial

Official title:

A Multicenter, Open-Label, Single-Arm Study to Evaluate a Titration Regimen for Patiromer in Heart Failure Patients With Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01130597
• Other study ID #: RLY5016-204
• Status: Completed
• Phase: Phase 2
• Start date: May 2010
• Est. completion date: September 2010

Study information

• Verified date: December 2015
• Source: Vifor Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the feasibility of individualized titration of patiromer according to serum potassium. This study also assessed the safety and tolerability of patiromer and the effects of patiromer on serum potassium in heart failure (HF) participants with chronic kidney disease (CKD).

Description:

This was an open-label, single-arm study to evaluate a titration regimen for patiromer in approximately 63 HF participants with CKD receiving one or more of the following: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or beta blockers (BBs). This study was considered to be exploratory. Upon successful completion of screening evaluations (-10 to -5 days prior to enrollment), all eligible participants were assigned at Baseline (Day 0 visit) to an initial dose of patiromer (20 g/day) and spironolactone (25 mg/day). Study visits for enrolled participants were scheduled for Days 3, 7, 14, 21, 28, 35, 42, 49 and 56. A follow-up visit occurred on Day 63. At selected study visits, patiromer or spironolactone doses may have been titrated. The study dosing algorithm was designed to maintain an individual's serum potassium value in the range of 4.0 - 5.1 mEq/L (based on local lab data). Any participant with a local laboratory serum potassium value < 3.5 or > 5.5 mEq/L on two consecutive scheduled study visits, despite titration of patiromer or spironolactone, were withdrawn from the study, permanently discontinued patiromer and spironolactone, and returned for a follow-up visit within 7 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Chronic HF clinically indicated to receive spironolactone therapy

2. Age 18 years or older

3. Local laboratory serum potassium values of 4.3 - 5.1 mEq/L at screening and baseline

4. CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 at screening based on central lab creatinine measurement)

5. On at least one of the following HF therapies: ACEI, ARB, or BB

6. Females of child-bearing potential must be non-lactating, must have a negative serum pregnancy test at screening, and must have used a highly effective form of contraception for at least 3 months before study drug administration, during the study, and for one month after study completion

7. Male participants and/or their female partners of child-bearing potential must use a highly effective form of contraception during the study and for 3 months after study completion

8. Provide their written informed consent prior to participation in the study

Exclusion Criteria:

1. History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery

2. Uncorrected primary severe valvular disease, known obstructive or restrictive cardiomyopathy, uncontrolled or hemodynamically unstable arrhythmia

3. Coronary-artery bypass graft, percutaneous intervention (e.g., cardiac, cerebrovascular, aortic), or major surgery including thoracic and cardiac, within 3 months prior to baseline or anticipated need during study participation

4. Heart transplant recipient, or anticipated need for transplant during study participation

5. Any of the following events having occurred within 2 months prior to baseline:

unstable angina as judged by the Investigator, unresolved acute coronary syndrome, transient ischemic attack or stroke

6. Current dialysis participant, or anticipated need for dialysis during study participation

7. Prior kidney transplant, or anticipated need for transplant during study participation

8. Metastatic, late-stage or end-stage cancer with < 12 months life expectancy or at risk for tumor lysis syndrome

9. History of alcoholism or drug/chemical abuse within 1 year

10. Sustained systolic blood pressure > 180 or < 90 mmHg

11. Liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] > 3 times upper limit of normal

12. Loop and thiazide diuretics that have not been stable for at least 21 days prior to baseline or not anticipated to remain stable during study participation

13. Use of any intravenous cardiac medications within 21 days prior to baseline, or their anticipated need during study participation

14. Current use of polymer-based drugs (e.g., sevelamer, sodium polystyrene sulfonate, colesevelam, colestipol), phosphate binders (e.g., lanthanum carbonate), or other potassium binders, or their anticipated need during study participation

15. Use of potassium sparing medication including aldosterone antagonists or potassium supplements in the last 21 days prior to baseline

16. Use of any investigational medication within 30 days or 5 half-lives, whichever is longer, prior to baseline

17. Participants who have taken investigational product in this study, or a previous patiromer study

18. Inability to consume the study medication, or, in the opinion of the Investigator, inability to comply with the protocol

19. In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, serious intercurrent illness, or extenuating circumstance occurring or persisting, within 30 days prior to baseline, that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results

Related Conditions & MeSH terms

• Heart Failure
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• patiromer
Active investigational drug
• spironolactone

Locations

Country	Name	City	State
Georgia	Investigator Site 11	Tbilisi
Georgia	Investigator Site 12	Tbilisi
Georgia	Investigator Site 13	Tbilisi
Georgia	Investigator Site 14	Tbilisi
Georgia	Investigator Site 15	Tbilisi
Georgia	Investigator Site 16	Tbilisi
Georgia	Investigator Site 17	Tbilisi
Georgia	Investigator Site 18	Tbilisi
Slovenia	Investigator Site 25	Golnik
Slovenia	Investigator Site 27	Izola
Slovenia	Investigator Site 21	Ljubljana
Slovenia	Investigator Site 22	Maribor
Slovenia	Investigator Site 26	Slovenj Gradec

Sponsors (1)

Lead Sponsor	Collaborator
Relypsa, Inc.

Countries where clinical trial is conducted

Georgia,  Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment		56 days
Secondary	Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4		28 Days
Secondary	Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8		56 Days
Secondary	Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4		28 Days
Secondary	Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8		56 Days
Secondary	Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment		56 Days
Secondary	Mean Dose of Patiromer at End of Treatment		56 Days
Secondary	Percentage of Participants Requiring Patiromer Uptitration		56 Days
Secondary	Percentage of Participants Requiring Patiromer Downtitration		56 Days
Secondary	Median Time to First Patiromer Dose Titration		56 Days
Secondary	Mean Number of Patiromer Titrations		56 Days
Secondary	Mean Patiromer Dose at Week 1		Up to Week 1
Secondary	Mean Patiromer Dose at Week 4		Up to Week 4
Secondary	Mean Patiromer Dose at Week 8		Up to Week 8
Secondary	Mean Change From Baseline in Serum Potassium to End of Treatment		56 Days
Secondary	Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L)		56 Days
Secondary	Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day		56 Days
Secondary	Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR = 30 mg/g at Baseline		Baseline and Day 28
Secondary	Change in ACR From Baseline to Week 8 Among Participants With Urine ACR = 30 mg/g at Baseline		Baseline and Day 56

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