RLY5016 in the Treatment of Hyperkalemia in Patients With Hypertension and Diabetic Nephropathy (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: September 13, 2013
Last verified: September 2013

June 9, 2011
September 13, 2013
May 2011
May 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01371747 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
RLY5016 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 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

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
Not Provided
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: RLY5016 + Losartan
    RLY5016 dose: 10 g/d, 20 g/d, and 30 g/d, oral, twice daily; Losartan dose: 100 mg/d, oral, once daily
  • Drug: RLY5016 + ACEi and/or ARB + Spironolactone
    RLY5016 dose: 10 g/d, 20 g/d, and 30 g/d, oral, twice daily; ACEi and/or ARB dose: current; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily
  • Drug: RLY5016 + Losartan
    RLY5016 dose: 30 g/d and 40 g/d, oral, twice daily; Losartan dose: 100 mg/d, oral, once daily
  • Drug: RLY5016 + ACEi and/or ARB + Spironolactone
    RLY5016 dose: 30 g/d and 40 g/d, oral, twice daily; ACEi and/or ARB dose: current; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily
  • Experimental: Stratum 1
    patients with serum potassium >5.0-5.5 mEq/L
    Interventions:
    • Drug: RLY5016 + Losartan
    • Drug: RLY5016 + ACEi and/or ARB + Spironolactone
  • Experimental: Stratum 2
    patients with serum potassium >5.5-<6.0 mEq/L
    Interventions:
    • Drug: RLY5016 + Losartan
    • Drug: RLY5016 + ACEi and/or ARB + Spironolactone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
306
June 2013
May 2013   (final data collection date for primary outcome measure)

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
Both
30 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Croatia,   Georgia,   Hungary,   Serbia,   Slovenia
 
NCT01371747
RLY5016-205, 2011-000165-12
No
Relypsa, Inc.
Relypsa, Inc.
Not Provided
Study Director: Yuri Stasiv Relypsa, Inc.
Relypsa, Inc.
September 2013

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