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

Phase 2

Completed

• Conditions: Heart Failure
• Interventions: Drug: patiromer; Drug: spironolactone

• Registration Number: NCT01130597
• Lead Sponsor: Relypsa, Inc.

Brief 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).

Detailed 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 5.5 mEq/L on two consecutive scheduled study visits, despite titration of patiromer or spironolactone, were withdrawn from the study, permanently discontinued patiromer and spironolactone, and returned for a follow-up visit within 7 days.

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-05-24
• Study First Submitted QC: 2010-05-24
• Study First Posted: 2010-05-26
• Primary Completion: 2010-09
• Study Completion: 2010-09
• Disposition First Submitted: 2014-10-30
• Disposition First Submitted QC: 2014-10-30
• Disposition First Posted: 2014-11-06
• Results First Submitted: 2015-11-11
• Status Verified: 2015-12
• Results First Submitted QC: 2015-12-21
• Results First Posted: 2016-01-28
• Last Update Submitted: 2021-05-10
• Last Update Posted: 2021-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
patiromer	patiromer	spironolactone + patiromer
patiromer	spironolactone	spironolactone + patiromer

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment	56 days

Secondary Outcome Measures

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

Trial Locations

Locations (13)

Investigator Site 11; 🇬🇪 Tbilisi, Georgia

Investigator Site 12; 🇬🇪 Tbilisi, Georgia

Investigator Site 22; 🇸🇮 Maribor, Slovenia

Investigator Site 14; 🇬🇪 Tbilisi, Georgia

Investigator Site 27; 🇸🇮 Izola, Slovenia

Investigator Site 17; 🇬🇪 Tbilisi, Georgia

Investigator Site 26; 🇸🇮 Slovenj Gradec, Slovenia

Investigator Site 16; 🇬🇪 Tbilisi, Georgia

Investigator Site 13; 🇬🇪 Tbilisi, Georgia

Investigator Site 18; 🇬🇪 Tbilisi, Georgia

Investigator Site 25; 🇸🇮 Golnik, Slovenia

Investigator Site 15; 🇬🇪 Tbilisi, Georgia

Investigator Site 21; 🇸🇮 Ljubljana, Slovenia