Evaluation of RLY5016 Titration in Heart Failure Patients With Chronic Kidney Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Relypsa, Inc.
ClinicalTrials.gov Identifier:
NCT01130597
First received: May 24, 2010
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to evaluate the feasibility of individualized titration of RLY5016 according to serum potassium. This study will also assess the safety and tolerability of RLY5016 and the effects of RLY5016 on serum potassium in heart failure patients with chronic kidney disease.


Condition Intervention Phase
Heart Failure
Drug: RLY5016 + Spironolactone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Multicenter, Open-Label, Single-Arm Study to Evaluate a Titration Regimen for RLY5016 in Heart Failure Patients With Chronic Kidney Disease

Resource links provided by NLM:


Further study details as provided by Relypsa, Inc.:

Primary Outcome Measures:
  • Proportion of patients with serum potassium in the normal range of 3.5 - 5.5 mEq/L at the end of the study [ Time Frame: 64 days ] [ Designated as safety issue: Yes ]

Enrollment: 63
Study Start Date: May 2010
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RLY5016
Open Label
Drug: RLY5016 + Spironolactone
Active investigational drug

Detailed Description:

This is an open-label, single-arm study to evaluate a titration regimen for RLY5016 in approximately 60 heart failure patients with chronic kidney disease receiving one or more of the following: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or beta blockers (BBs). This study is considered to be exploratory.

Upon successful completion of screening evaluations (-10 to -5 days prior to enrollment) all eligible patients will be assigned at Baseline (Day 0 visit) to an initial dose of RLY5016 (20 g/day) and spironolactone (25 mg/day).

Study visits for enrolled patients will be scheduled for Days 3, 7, 14, 21, 28, 35, 42, 49, and 56. A follow-up visit will occur on Day 63.

At selected study visits RLY5016 or spironolactone doses may be titrated. The study dosing algorithm is 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 patient with a local lab serum potassium value < 3.5 or > 5.5 mEq/L on two consecutive scheduled study visits, despite titration of RLY5016 or spironolactone, must be withdrawn from the study, permanently discontinue RLY5016 and spironolactone, and return for a follow-up visit in 7 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Chronic heart failure clinically indicated to receive spironolactone therapy
  2. Age 18 years or older
  3. Local lab serum potassium values of 4.3 - 5.1 mEq/L at screening and baseline
  4. Chronic kidney disease (estimated GFR < 60 mL/min/1.73m2 at screening based on central lab creatinine measurement)
  5. On at least one of the following heart failure 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 patients 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 patient, 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. Patients who have taken investigational product in this study, or a previous RLY5016 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 patient or affect the validity of the trial results
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01130597

Locations
Georgia
JSC National Center of Therapy
Tbilisi, Georgia
EOPL Tbilisi State Medical University
Tbilisi, Georgia
Emergency Cardiology Center by Academician G.Chapidze LTD
Tbilisi, Georgia
Diagnostic Services Clinic, LTD
Tbilisi, Georgia
Multiprofile Clinical Hospital of Tbilisi #2, LTD
Tbilisi, Georgia
Cardiology Clinic LTD
Tbilisi, Georgia
The Clinic of Angiocardiology "ADAPTI" LTD
Tbilisi, Georgia
Medical Center "CITO" LTD
Tbilisi, Georgia
Slovenia
General Hospital Celje
Celje, Slovenia
The University Clinic of Pulmonary and Allergic Diseases Golnik
Golnik, Slovenia
General Hospital Izola
Izola, Slovenia
University Medical Center Ljubljana
Ljubljana, Slovenia
University Medical Center
Maribor, Slovenia
General Hospital Slovenj Gradec
Slovenj Gradec, Slovenia
Hospital Topolsica
Topolsica, Slovenia
Sponsors and Collaborators
Relypsa, Inc.
Investigators
Study Director: I-Zu Huang, MD Relypsa, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Relypsa, Inc.
ClinicalTrials.gov Identifier: NCT01130597     History of Changes
Other Study ID Numbers: RLY5016-204
Study First Received: May 24, 2010
Last Updated: May 23, 2012
Health Authority: Slovenia: Agency for Medicinal Products - Ministry of Health
Georgia: Ministry of Health

Keywords provided by Relypsa, Inc.:
HF
Heart failure
hyperkalemia
chronic kidney disease
prevention of hyperkalemia in heart failure patients

Additional relevant MeSH terms:
Heart Failure
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Heart Diseases
Cardiovascular Diseases
Urologic Diseases
Renal Insufficiency
Spironolactone
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014