Patiromer in the Treatment of Hyperkalemia in Patients With Hypertension and Diabetic Nephropathy (AMETHYST-DN)

• Status: Completed
• Trial end date: 2013-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This study determined the optimal starting dose of patiromer in treating hyperkalemia in participants with hypertension and diabetic nephropathy who were already receiving ACEI and/or ARB drugs, with or without spironolactone. This study also evaluated the efficacy and safety of patiromer and the long term use of patiromer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Relypsa, Inc.
• Treatments: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Losartan; Spironolactone

Criteria

Inclusion Criteria:

1. Age 30 - 80 years old at screening (S1)

2. Type 2 diabetes mellitus (T2DM) diagnosed after age 30 which has been treated with oral medications or insulin for at least 1 year prior to S1

3. Chronic kidney disease (CKD): estimated glomerular filtration rate (eGFR) 15 - < 60 mL/min/1.73m2 at screening based on central lab serum creatinine measurement (except for participants with hyperkalemia at S1), whose eligibility will be assessed based on local lab eGFR value)

4. Urine albumin/creatinine ratio (ACR):

1. Cohorts 1 and 2: urine ACR ≥ 30 mg/g at S1 AND average urine ACR ≥ 30 mg/g at the beginning of Run-In Period (R0) based on up to three ACR values obtained starting at S1 and ending at the R0 Visit

2. Cohort 3: not applicable

5. Local laboratory serum potassium (K+) values of:

1. Cohorts 1 and 2: 4.3 - 5.0 mEq/L at S1; AND 4.5 - 5.0 mEq/L at R0; AND > 5.0 - < 6.0 mEq/L at randomization to patiromer (Baseline, T0 Visit)

2. Cohort 3: > 5.0 - < 6.0 mEq/L at S1 OR at R0 after same day confirmation

6. Must be receiving an ACEI and/or ARB for at least 28 days prior to screening

7. Average systolic blood pressure (SBP) ≥ 130 - < 180 mmHg AND average DBP ≥ 80 - < 110 mmHg (sitting) at both screening and R0 (as applicable)

8. 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 patiromer administration, during the study, and for one month after study completion

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

Exclusion Criteria:

1. Type 1 diabetes mellitus

2. Central lab hemoglobin A1c > 12% at Screening 1 (S1) (except for Cohort 3 participants who are hyperkalemic at S1)

3. Emergency treatment for T2DM within the last 3 months

4. A confirmed SBP > 180 mmHg or diastolic blood pressure (DBP) > 110 mmHg at any time during SI or Run-In Period or at Baseline T0 Visit

5. Central lab serum magnesium < 1.4 mg/dL (< 0.58 mmol/L) at screening (Cohort 3 participants will be evaluated based on local lab serum magnesium measurement)

6. Central lab urine ACR ≥ 10000 mg/g at screening (except for Cohort 3 participants who are hyperkalemic at S1)

7. Confirmed diagnosis or history of renal artery stenosis (unilateral or bilateral)

8. Diabetic gastroparesis

9. Non-diabetic chronic kidney disease

10. History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery (e.g., large bowel resection)

11. Current diagnosis of NYHA (New York Heart Association) Class III or IV heart failure

12. Body mass index (BMI) ≥ 40 kg/m2

13. Any of the following events having occurred within 2 months prior to screening:

unstable angina as judged by the Principal Investigator (PI), unresolved acute coronary syndrome, cardiac arrest or clinically significant ventricular arrhythmias, transient ischemic attack or stroke, use of any intravenous cardiac medication

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

15. Active cancer, currently on cancer treatment or history of cancer in the past 2 years except for non-melanocytic skin cancer which is considered cured

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

17. Central lab liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] > 3 times upper limit of normal at S1 (except for Cohort 3 patients with hyperkalemia at S1, who will have local lab ALT and AST)

18. Loop and thiazide diuretics or other antihypertensive medications (calcium channel blocker, beta-blocker, alpha-blocker, or centrally acting agent) that have not been stable for at least 28 days prior to screening or not anticipated to remain stable during study participation

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

20. Current use of lithium

21. Use of potassium sparing medications, including aldosterone antagonists (e.g., spironolactone), drospirenone, potassium supplements, bicarbonate or baking soda in the last 7 days prior to screening

22. Use of any investigational product within 30 days or 5 half-lives, whichever is longer, prior to screening

23. Inability to consume the investigational product, or, in the opinion of the Investigator, inability to comply with the protocol

24. In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, or serious intercurrent illness that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results