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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Relypsa, Inc.
ClinicalTrials.gov Identifier:
NCT01371747
First received: June 9, 2011
Last updated: November 11, 2015
Last verified: November 2015

June 9, 2011
November 11, 2015
June 2011
May 2013   (final data collection date for primary outcome measure)
Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group [ Time Frame: Baseline to Week 4 or First Titration ] [ Designated as safety issue: No ]
Mean change in serum potassium from baseline to week 4 or prior to the initiation of RLY5016 dose titration (if occurs before week 4) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01371747 on ClinicalTrials.gov Archive Site
  • Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group [ Time Frame: Baseline to Week 8 or First Titration ] [ Designated as safety issue: No ]
  • Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group [ Time Frame: Baseline to Day 3 ] [ Designated as safety issue: No ]
  • Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Mean Change in Serum Potassium From End of Treatment to Follow-up Visits Plus 7 Days [ Time Frame: End of Treatment to Following up Visit Plus 7 Days ] [ Designated as safety issue: No ]
  • Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Mean change in serum potassium from baseline to week 8 or prior to the initiation of RLY5016 dose titration [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients maintaining the starting RLY5016 dose at week 4 and 8 [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • Mean change in serum potassium from baseline to post-baseline visits [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients requiring RLY5016 titration [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
  • Mean time to first RLY5016 titration [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • Mean number of RLY5016 titrations [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients who discontinue from the study due to high serum potassium withdrawal criteria [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • Mean change in blood pressure from screening to week 4 and 8 [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Mean change in urine albumin to creatinine ratio (ACR) from screening to week 4 and 8 [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients with ≥ 35% reduction in urine ACR from screening to week 4 and 8 [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients with urine ACR ≥ 500 mg/g at screening who achieve ACR < 500 mg/g at week 4 and 8 [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Patiromer in the Treatment of Hyperkalemia in Patients With Hypertension and Diabetic Nephropathy (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 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.

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) 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
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Kidney Disease
  • Hypertension
  • Hyperkalemia
  • Drug: patiromer
    Patiromer starting dose: 8.4 g/day, 16.8 g/day, and 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.
    Other Names:
    • RLY5016 for Oral Suspension
    • Veltassa
  • Drug: patiromer
    Patiromer starting dose: 16.8 g/day, 25.2 g/day and 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.
    Other Names:
    • RLY5016 for Oral Suspension
    • Veltassa
  • Experimental: Stratum 1
    Participants with baseline serum potassium > 5.0 - 5.5 mEq/L (milliequivalent)
    Intervention: Drug: patiromer
  • Experimental: Stratum 2
    Participants with baseline serum potassium > 5.5 - < 6.0 mEq/L
    Intervention: Drug: patiromer
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
324
June 2013
May 2013   (final data collection date for primary outcome measure)

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
Both
30 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Croatia,   Georgia,   Hungary,   Serbia,   Slovenia
Austria
 
NCT01371747
RLY5016-205, 2011-000165-12
No
Not Provided
Not Provided
Relypsa, Inc.
Relypsa, Inc.
Not Provided
Study Director: Director Clinical Operations Relypsa, Inc.
Relypsa, Inc.
November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP