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

A Multicenter, Randomized, Open-Label, Dose Ranging Study to Evaluate the Efficacy and Safety of Patiromer 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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Chronic Kidney Disease; Hyperkalemia
• Intervention / Treatment: Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: losartan; Drug: spironolactone

Detailed Description

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

The study consisted of the following periods:

• Screening: Up to 10 days (1 visit)
• Run-in for those who were not hyperkalemic at screening (Cohorts 1 and 2): up to 4 weeks (1 to 4 visits)
• Patiromer Treatment Initiation: first 8 weeks of patiromer treatment (a minimum of 10 visits)
• Patiromer Long-Term Maintenance: additional 44 weeks of patiromer treatment up to a total of one year (minimum of 11 additional visits)
• Follow-up (after patiromer discontinuation): 1 week (2 visits) OR 4 weeks (5 visits) depending on the final serum potassium level

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Phase 2

Contacts and Locations

Study Locations

• Croatia
  • Karlovac, Croatia, 47000
    • Investigator site 201
  • Osijek, Croatia, 31000
    • Investigator site 207
  • Rijeka, Croatia, 51000
    • Investigator site 203
  • Zagreb, Croatia, 10000
    • Investigator site 202
  • Zagreb, Croatia, 10000
    • Investigator site 204
  • Zagreb, Croatia, 10000
    • Investigator site 208
• Georgia
  • Tbilisi, Georgia, 0102
    • Investigator Site 305
  • Tbilisi, Georgia, 0144
    • Investigator Site 309
  • Tbilisi, Georgia, 0159
    • Investigator site 301
  • Tbilisi, Georgia, 0159
    • Investigator Site 302
  • Tbilisi, Georgia, 0159
    • Investigator Site 303
  • Tbilisi, Georgia, 0159
    • Investigator Site 304
  • Tbilisi, Georgia, 0159
    • Investigator Site 306
  • Tbilisi, Georgia, 0159
    • Investigator Site 307
  • Tbilisi, Georgia, 0159
    • Investigator Site 310
  • Tbilisi, Georgia, 0159
    • Investigator Site 311
  • Tbilisi, Georgia, 0186
    • Investigator Site 308
• Hungary
  • Budapest, Hungary, 1097
    • Investigator Site 508
  • Budapest, Hungary, 1106
    • Investigator Site 502
  • Budapest, Hungary, H-1041
    • Investigator Site 514
  • Budapest, Hungary, H-1097
    • Investigator Site 513
  • Budapest, Hungary, H-1115
    • Investigator Site 517
  • Gyor, Hungary, H-9024
    • Investigator Site 522
  • Hatvan, Hungary, 3000
    • Investigator Site 523
  • Jaszbereny, Hungary, H-5100
    • Investigator Site 515
  • Kistarcsa, Hungary, H-2143
    • Investigator Site 506
  • Kisvarda, Hungary, 4600
    • Investigator Site 503
  • Mosonmagyarovar, Hungary, H-9200
    • Investigator Site 510
  • Szekesfehervar, Hungary, H-8000
    • Investigator Site 504
  • Szikszo, Hungary, 3800
    • Investigator Site 505
  • Veszprem, Hungary, H-8200
    • Investigator Site 507
• Serbia
  • Belgrade, Serbia, 11000
    • Investigator Site 601
  • Belgrade, Serbia, 11000
    • Investigator Site 602
  • Belgrade, Serbia, 11000
    • Investigator Site 604
  • Belgrade, Serbia, 11000
    • Investigator Site 605
  • Novi Sad, Serbia, 21000
    • Investigator Site 603
  • Zrenjanin, Serbia, 23000
    • Investigator Site 607
• Slovenia
  • Celje, Slovenia, 3000
    • Investigator Site 703
  • Golnik, Slovenia, 4204
    • Investigator Site 706
  • Jesenice, Slovenia, 4270
    • Investigator Site 708
  • Maribor, Slovenia, 2000
    • Investigator Site 701
  • Slovenj Gradec, Slovenia, 2380
    • Investigator Site 704
  • Šempeter pri Gorici, Slovenia, 5290
    • Investigator Site 707

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stratum 1: 8.4 g/d patiromer; Participants with baseline serum potassium > 5.0 to 5.5 mEq/L (milliequivalent)	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 8.4 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 33.6 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 1: 16.8 g/d patiromer; Participants with baseline serum potassium > 5.0 to 5.5 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 8.4 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 33.6 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 1: 25.2 g/d patiromer; Participants with baseline serum potassium > 5.0 to 5.5 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 8.4 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 33.6 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 2: 16.8 g/d patiromer; Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 8.4 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 33.6 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 2: 25.2 g/d patiromer; Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 8.4 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 33.6 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 2: 33.6 g/d patiromer; Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 8.4 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 33.6 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: Veltassa; RLY5016 for Oral Suspension; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group	Least square mean changes from Baseline to Week 4/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.	Baseline to Week 4 or First Titration which could occur at any scheduled study visit after patiromer initiation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group	Least squares mean changes from Baseline to Week 8/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.	Baseline to Week 8 or First Titration which could occur at any scheduled study visit after patiromer initiation.
Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group	Least squares mean changes from Baseline to Day 3 were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.	Baseline to Day 3
Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group		Baseline to Week 52
Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days		Week 52 or Last Patiromer Dose (if Occurred before Week 52) to Following up Visit Plus 7 Days
Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group		Baseline to Week 8
Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group		Baseline to Week 8
Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group		Baseline to Week 8
Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group		Baseline to Week 52

Collaborators and Investigators

• Sponsor: Relypsa, Inc.

Publications and helpful links

General Publications

• Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.
• Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, Garza D, Stasiv Y, Zawadzki R, Berman L, Bushinsky DA; AMETHYST-DN Investigators. Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial. JAMA. 2015 Jul 14;314(2):151-61. doi: 10.1001/jama.2015.7446. Erratum In: JAMA. 2015 Aug 18;314(7):731. Dosage error in article text.
• Bakris GL, Woods SD, Alvarez PJ, Arthur SP, Kumar R. Hyperkalemia Management in Older Adults With Diabetic Kidney Disease Receiving Renin-Angiotensin-Aldosterone System Inhibitors: A Post Hoc Analysis of the AMETHYST-DN Clinical Trial. Kidney Med. 2021 Mar 13;3(3):360-367.e1. doi: 10.1016/j.xkme.2021.01.005. eCollection 2021 May-Jun.
• Pitt B, Bakris GL, Weir MR, Freeman MW, Lainscak M, Mayo MR, Garza D, Zawadzki R, Berman L, Bushinsky DA. Long-term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin-converting enzymes/angiotensin receptor blockers: results from AMETHYST-DN. ESC Heart Fail. 2018 Aug;5(4):592-602. doi: 10.1002/ehf2.12292. Epub 2018 May 16.

Helpful Links

• Relypsa company website

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (Estimate): June 13, 2011

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hypertension; Chronic Kidney Disease; Treatment of Hyperkalemia; Hyperkalemia; Diabetic Nephropathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Renal Insufficiency; Water-Electrolyte Imbalance; Hypertension; Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Hyperkalemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Losartan; Spironolactone
• Other Study ID Numbers: RLY5016-205; 2011-000165-12 (EudraCT Number)