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Chronic Kidney DiseasePhase 2AMETHYST-DNNCT01371747

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

A Phase 2 study testing patiromer, losartan and spironolactone in people with Chronic Kidney Disease and Hypertension, run by Relypsa, Inc. at 43 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 30 to 80 years
Conditions the study is for
Chronic Kidney Disease, Hypertension, Hyperkalemia
What is being tested?
patiromer, losartan and spironolactone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
324 participants
Where
43 sitesin 5 countries
Study dates
Jun 2011to Jun 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 - < 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)
  • Urine albumin/creatinine ratio (ACR):
  • 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
  • Cohort 3: not applicable
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  • Local laboratory serum potassium (K+) values of:
  • 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)
  • Cohort 3: > 5.0 - < 6.0 mEq/L at S1 OR at R0 after same day confirmation
  • Must be receiving an ACEI and/or ARB for at least 28 days prior to screening
  • Average systolic blood pressure (SBP) ≥ 130 - < 180 mmHg AND average DBP ≥ 80 - < 110 mmHg (sitting) at both screening and R0 (as applicable)
  • 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
  • Provide their written informed consent prior to participation in the study

Who cannot join

  • Type 1 diabetes mellitus
  • Central lab hemoglobin A1c > 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 < 1.4 mg/dL (< 0.58 mmol/L) at screening (Cohort 3 participants will be evaluated based on local lab serum magnesium measurement)
  • Central lab urine ACR ≥ 10000 mg/g at screening (except for Cohort 3 participants who are hyperkalemic at S1)
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  • Confirmed diagnosis or history of renal artery stenosis (unilateral or bilateral)
  • Diabetic gastroparesis
  • Non-diabetic chronic kidney disease
  • History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery (e.g., large bowel resection)
  • Current diagnosis of NYHA (New York Heart Association) Class III or IV heart failure
  • Body mass index (BMI) ≥ 40 kg/m2
  • 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
  • Prior kidney transplant, or anticipated need for transplant during study participation
  • 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
  • History of alcoholism or drug/chemical abuse within 1 year
  • 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)
  • 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

Trial locations and contacts

43 sites in 5 countries.

43 sites in 5 countries

Hungary14 sites

  • Investigator Site 508

    Budapest, 1097

  • Investigator Site 502

    Budapest, 1106

  • Investigator Site 514

    Budapest, H-1041

  • Investigator Site 513

    Budapest, H-1097

  • Investigator Site 517

    Budapest, H-1115

  • Investigator Site 522

    Győr, H-9024

  • Investigator Site 523

    Hatvan, 3000

  • Investigator Site 515

    Jászberény, H-5100

  • Investigator Site 506

    Kistarcsa, H-2143

  • Investigator Site 503

    Kisvárda, 4600

  • Investigator Site 510

    Mosonmagyaróvár, H-9200

  • Investigator Site 504

    Székesfehérvár, H-8000

  • Investigator Site 505

    Szikszó, 3800

  • Investigator Site 507

    Veszprém, H-8200

Other trials in Hungary

Georgia11 sites

  • Investigator Site 305

    Tbilisi, 0102

  • Investigator Site 309

    Tbilisi, 0144

  • Investigator site 301

    Tbilisi, 0159

  • Investigator Site 302

    Tbilisi, 0159

  • Investigator Site 303

    Tbilisi, 0159

  • Investigator Site 304

    Tbilisi, 0159

  • Investigator Site 306

    Tbilisi, 0159

  • Investigator Site 307

    Tbilisi, 0159

  • Investigator Site 310

    Tbilisi, 0159

  • Investigator Site 311

    Tbilisi, 0159

  • Investigator Site 308

    Tbilisi, 0186

Other trials in Georgia

Croatia6 sites

  • Investigator Site 201

    Karlovac, 47000

  • Investigator Site 207

    Osijek, 31000

  • Investigator Site 203

    Rijeka, 51000

  • Investigator Site 202

    Zagreb, 10000

  • Investigator Site 204

    Zagreb, 10000

  • Investigator Site 208

    Zagreb, 10000

Other trials in Croatia

Serbia6 sites

  • Investigator Site 601

    Belgrade, 11000

  • Investigator Site 602

    Belgrade, 11000

  • Investigator Site 604

    Belgrade, 11000

  • Investigator Site 605

    Belgrade, 11000

  • Investigator Site 603

    Novi Sad, 21000

  • Investigator Site 607

    Zrenjanin, 23000

Other trials in Serbia

Slovenia6 sites

  • Investigator Site 703

    Celje, 3000

  • Investigator Site 706

    Golnik, 4204

  • Investigator Site 708

    Jesenice, 4270

  • Investigator Site 701

    Maribor, 2000

  • Investigator Site 707

    Sempeter pri Gorici, 5290

  • Investigator Site 704

    Slovenj Gradec, 2380

Other trials in Slovenia

About this study

Official title: 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.

Read the 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
Being tested
patiromer, losartan, spironolactone
Keywords
Hyperkalemia, Chronic Kidney Disease, Treatment of Hyperkalemia, Hypertension, Diabetic Nephropathy
Medical subject headings
Renal Insufficiency, Chronic, Hypertension, Hyperkalemia, Diabetic Nephropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • patiromerDrug

    Also called RLY5016 for Oral Suspension, Veltassa

    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)

  • patiromerDrug

    Also called RLY5016 for Oral Suspension, Veltassa

    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)

  • patiromerDrug

    Also called RLY5016 for Oral Suspension, Veltassa

    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)

  • patiromerDrug

    Also called RLY5016 for Oral Suspension, Veltassa

    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)

  • patiromerDrug

    Also called RLY5016 for Oral Suspension, Veltassa

    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)

  • patiromerDrug

    Also called RLY5016 for Oral Suspension, Veltassa

    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)

  • losartanDrug

    losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1)

  • spironolactoneDrug

    Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)

Study groups in NCT01371747
Study groupRoleWhat they receive
Stratum 1: 8.4 g/d patiromerExperimentalParticipants with baseline serum potassium > 5.0 to 5.5 mEq/L (milliequivalent)
Receives: Drug: patiromer; Drug: losartan; Drug: spironolactone
Stratum 1: 16.8 g/d patiromerExperimentalParticipants with baseline serum potassium > 5.0 to 5.5 mEq/L
Receives: Drug: patiromer; Drug: losartan; Drug: spironolactone
Stratum 1: 25.2 g/d patiromerExperimentalParticipants with baseline serum potassium > 5.0 to 5.5 mEq/L
Receives: Drug: patiromer; Drug: losartan; Drug: spironolactone
Stratum 2: 16.8 g/d patiromerExperimentalParticipants with baseline serum potassium > 5.5 to < 6.0 mEq/L
Receives: Drug: patiromer; Drug: losartan; Drug: spironolactone
Stratum 2: 25.2 g/d patiromerExperimentalParticipants with baseline serum potassium > 5.5 to < 6.0 mEq/L
Receives: Drug: patiromer; Drug: losartan; Drug: spironolactone
Stratum 2: 33.6 g/d patiromerExperimentalParticipants with baseline serum potassium > 5.5 to < 6.0 mEq/L
Receives: Drug: patiromer; Drug: losartan; Drug: spironolactone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to Week 4 or First Titration which could occur at any scheduled study visit after patiromer initiation.

Secondary outcomes (8)

  1. 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.

    Measured: Baseline to Week 8 or First Titration which could occur at any scheduled study visit after patiromer initiation.

  2. 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.

    Measured: Baseline to Day 3

  3. Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group

    Measured: Baseline to Week 52

  4. Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days

    Measured: Week 52 or Last Patiromer Dose (if Occurred before Week 52) to Following up Visit Plus 7 Days

  5. Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group

    Measured: Baseline to Week 8

  6. Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group

    Measured: Baseline to Week 8

  7. Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group

    Measured: Baseline to Week 8

  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

    Measured: Baseline to Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2011 (estimated)
  2. Study startJun 2011
  3. Primary completionMay 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
324 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01371747
Sponsor's protocol ID
RLY5016-205
Other IDs
2011-000165-12
Acronym
AMETHYST-DN
Status last verified
May 2021
First submitted
9 Jun 2011
Last updated
3 Jun 2021
Data monitoring committee
No

Publications

  • 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.

    PubMed 26172895

  • 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.

    PubMed 34136782

  • 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.

    PubMed 32588430

  • 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.

    PubMed 29767459

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing patiromer, losartan and spironolactone in people with Chronic Kidney Disease and Hypertension, run by Relypsa, Inc. at 43 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in Hungary, Georgia, Croatia, Serbia, Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Least Squares 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 which could occur at any scheduled study visit after patiromer initiation.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01371747, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2021.

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