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RLY5016 in the Treatment of Hyperkalemia in Patients With Hypertension and Diabetic Nephropathy (AMETHYST-DN)

Information source: Relypsa, Inc.
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chronic Kidney Disease; Hypertension; Hyperkalemia

Intervention: RLY5016 + Losartan (Drug); RLY5016 + ACEi and/or ARB + Spironolactone (Drug); RLY5016 + Losartan (Drug); RLY5016 + ACEi and/or ARB + Spironolactone (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Relypsa, Inc.

Official(s) and/or principal investigator(s):
Yuri Stasiv, Study Director, Affiliation: Relypsa, Inc.

Summary

RLY5016-205 is an open-label, randomized, dose ranging study to determine the optimal starting dose, efficacy and safety of RLY5016 in treating hyperkalemia in hypertensive patients with nephropathy due to type 2 diabetes mellitus (T2DM) receiving Angiotensin-converting Enzyme Inhibitor (ACEI) and/or Angiotensin II Receptor Blocker (ARB) drugs, with or without spironolactone. The study consists of the following periods:

- Screening: Up to 10 days (1 visit)

- Run-in: up to 4 weeks (1 to 4 visits)

- RLY5016 Treatment Initiation: first 8 weeks of RLY5016 treatment (a minimum of 10

visits)

- Long-Term Maintenance: additional 44 weeks of RLY5016 treatment up to a total of one

year (minimum of 11 additional visits)

- Follow-up (after RLY5016 discontinuation): 1 week (2 visits) OR 4 weeks (5 visits)

depending on the final serum potassium level

Clinical Details

Official title: A Multicenter, Randomized, Open-Label, Dose Ranging Study to Evaluate the Efficacy and Safety of RLY5016 in the Treatment of Hyperkalemia in Patients With Hypertension and Diabetic Nephropathy Receiving Angiotensin-converting Enzyme Inhibitor (ACEI) and/or Angiotensin II Receptor Blocker (ARB) Drugs, With or Without Spironolactone

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Mean change in serum potassium from baseline to week 4 or prior to the initiation of RLY5016 dose titration (if occurs before week 4)

Secondary outcome:

Mean change in serum potassium from baseline to week 8 or prior to the initiation of RLY5016 dose titration

Proportion of patients maintaining the starting RLY5016 dose at week 4 and 8

Mean change in serum potassium from baseline to post-baseline visits

Proportion of patients requiring RLY5016 titration

Mean time to first RLY5016 titration

Mean number of RLY5016 titrations

Proportion of patients who maintain serum potassium (K+) in the range of 3.5 - 5.5 mEq/L by visit and during the entire study treatment period

Proportion of patients who maintain serum K+ in the range of 4.0 - 5.0 mEq/L by visit and during the entire study treatment period

Proportion of patients who discontinue from the study due to high serum potassium withdrawal criteria

Mean change in blood pressure from screening to week 4 and 8

Mean change in urine albumin to creatinine ratio (ACR) from screening to week 4 and 8

Proportion of patients with ≥ 35% reduction in urine ACR from screening to week 4 and 8

Proportion of patients with urine ACR ≥ 500 mg/g at screening who achieve ACR < 500 mg/g at week 4 and 8

Eligibility

Minimum age: 30 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. 1. Age 30 - 80 years old at screening

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

3. Chronic kidney disease: eGFR 15 - < 60 mL/min/1. 73m2 at screening based on central

lab serum creatinine measurement (except for patients with hyperkalemia at S1, whose eligibility will be assessed based on local lab eGFR value) 4. 4. Urine ACR: 1. Cohorts 1 and 2: urine ACR ≥ 30 mg/g at screening (S1) AND average urine ACR ≥ 30 mg/g at the beginning of Run-In Period (R0) based on up to 3 ACR values obtained starting at S1 and ending at the R0 Visit 2. Cohort 3: not applicable 5. Local laboratory serum 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 RLY5016 (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 SBP ≥ 140 - < 180 mmHg OR average DBP ≥ 90 - < 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 RLY5016 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 S1 (except for Cohort 3 patients who are hyperkalemic at S1) 3. Emergency treatment for T2DM within the last 3 months 4. Diabetic gastroparesis 5. Non-diabetic chronic kidney disease 6. History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery (e. g., cholectomy) 7. Current diagnosis of NYHA Class III or IV heart failure 8. Body mass index (BMI) ≥ 40 kg/m2 9. Any of the following events having occurred within 2 months prior to screening: unstable angina as judged by the Investigator, unresolved acute coronary syndrome, cardiac arrest or clinically significant ventricular arrhythmias, transient ischemic attack or stroke, use of any intravenous cardiac medication 10. Prior kidney transplant, or anticipated need for transplant during study participation 11. Active cancer, currently on cancer treatment or history of cancer in the past two years except for non-melanocytic skin cancer which is considered cured 12. History of alcoholism or drug/chemical abuse within 1 year 13. Central lab liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] > 3 times upper limit of normal (except for Cohort 3 patients with hyperkalemia at S1, who will have local lab ALT and AST) 14. 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 15. 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 16. Current use of lithium 17. 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 18. Use of any investigational product within 30 days or 5 half-lives, whichever is longer, prior to screening 19. Inability to consume the investigational product, or, in the opinion of the Investigator, inability to comply with the protocol 20. 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 patient or affect the validity of the trial results

Locations and Contacts

Investigator Site 201, Karlovac 47000, Croatia

Investigator Site 207, Osijek 31000, Croatia

Investigator Site 203, Rijeka 51000, Croatia

Investigator Site 202, Zagreb 10000, Croatia

Investigator Site 204, Zagreb 10000, Croatia

Investigator Site 208, Zagreb 10000, Croatia

Investigator site 301, Tbilisi 0159, Georgia

Investigator Site 302, Tbilisi 0159, Georgia

Investigator Site 303, Tbilisi 0159, Georgia

Investigator Site 304, Tbilisi 0141, Georgia

Investigator Site 305, Tbilisi 0102, Georgia

Investigator Site 306, Tbilisi 0179, Georgia

Investigator Site 307, Tbilisi 0164, Georgia

Investigator Site 308, Tbilisi 0186, Georgia

Investigator Site 309, Tbilisi 0144, Georgia

Investigator Site 310, Tbilisi 0159, Georgia

Investigator Site 311, Tbilisi 0141, Georgia

Investigator Site 516, Baja H-6500, Hungary

Investigator Site 501, Budapest 1083, Hungary

Investigator Site 502, Budapest 1106, Hungary

Investigator Site 508, Budapest 1097, Hungary

Investigator Site 513, Budapest 1097, Hungary

Investigator Site 514, Budapest H-1041, Hungary

Investigator Site 517, Budapest H-1115, Hungary

Investigator Site 518, Debrecen H-4032, Hungary

Investigator Site 522, Gyor H-9024, Hungary

Investigator Site 523, Hatvan 3000, Hungary

Investigator Site 515, Jaszbereny H-5100, Hungary

Investigator Site 511, Kecskemet 6000, Hungary

Investigator Site 506, Kistarcsa 2143, Hungary

Investigator Site 503, Kisvarda 4600, Hungary

Investigator Site 510, Mosonmagyarovar 9200, Hungary

Investigator Site 520, Pecs H-7624, Hungary

Investigator Site 504, Szekesfehervar 8000, Hungary

Investigator Site 505, Szikszo 3800, Hungary

Investigator Site 507, Veszprem 8200, Hungary

Investigator Site 601, Belgrade 11000, Serbia

Investigator Site 602, Belgrade 11000, Serbia

Investigator Site 604, Belgrade 11000, Serbia

Investigator Site 605, Belgrade 11000, Serbia

Investigator Site 606, Belgrade 11000, Serbia

Investigator Site 603, Novi Sad 21000, Serbia

Investigator Site 607, Zrenjanin 23000, Serbia

Investigator Site 703, Celje 3000, Slovenia

Investigator Site 706, Golnik 4204, Slovenia

Investigator Site 705, Izola 6310, Slovenia

Investigator Site 708, Jesenice 4270, Slovenia

Investigator Site 702, Ljubljana 1000, Slovenia

Investigator Site 701, Maribor 2000, Slovenia

Investigator Site 704, Slovenj Gradec 2380, Slovenia

Investigator Site 707, Šempeter pri Gorici 5290, Slovenia

Additional Information

Relypsa company website

Starting date: May 2011
Last updated: October 30, 2014

Page last updated: August 23, 2015

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