Phase 2
N=306
Patiromer in the Treatment of Hyperkalemia in Patients With Hypertension and Diabetic Nephropathy (AMETHYST-DN)
Chronic Kidney Disease · Hypertension · Hyperkalemia
Bottom Line
View on ClinicalTrials.gov: NCT01371747 ↗Enrolled (actual)
306
Serious AEs
14.5%
Results posted
Dec 2015
Primary outcome: Primary: Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group — -0.35; -0.51; -0.55; -0.87 mEq/L — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- patiromer (Drug); losartan (Drug); spironolactone (Drug)
- Age
- Adult, Older Adult · 30+ yrs
- Sex
- All
- Sponsor
- Relypsa, Inc.
- Primary completion
- May 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group |
-0.35; -0.51; -0.55; -0.87; -0.97; -0.92 | <0.001 sig |
| SECONDARY Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group |
-0.35; -0.47; -0.54; -0.88; -0.95; -0.91 | <0.001 sig |
| SECONDARY Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group |
-0.26; -0.28; -0.31; -0.65; -0.59; -0.53 | <0.001 sig |
| SECONDARY Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group |
-0.54; -0.44; -0.50; -1.00; -0.96; -1.17 | — |
| SECONDARY Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days |
0.36; 0.22; 0.30; 0.41; 0.39; 0.58 | — |
| SECONDARY Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group |
100; 100; 98.4; 91.7; 95.8; 95.5 | — |
| SECONDARY Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group |
95.2; 90.8; 81.3; 79.2; 91.7; 77.3 | — |
| SECONDARY Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group |
4; 4; 4; 8; 7.5; 8 | — |
| SECONDARY Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group |
86.3; 81.6; 88.9; 86.7; 89.5; 93.3 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Age 30 - 80 years old at screening (S1)
- 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
- Chronic kidney disease (CKD): estimated glomerular filtration rate (eGFR) 15 - 5.0 - 5.0 - 12% at Screening 1 (S1) (except for Cohort 3 participants who are hyperkalemic at S1)
- Emergency treatment for T2DM within the last 3 months
- 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
- Central lab serum magnesium 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)
- 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
- 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
- Current use of lithium
- 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
- Use of any investigational product within 30 days or 5 half-lives, whichever is longer, prior to screening
- Inability to consume the investigational product, or, in the opinion of the Investigator, inability to comply with the protocol
- 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
Data sourced from ClinicalTrials.gov (NCT01371747). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.