A Two-Part, Single-Blind, Phase 3 Study Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalemia (OPAL) (OPAL)

A Two-Part, Single-Blind, Phase 3 Study Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalemia

The purpose of this study was to evaluate the efficacy and safety of patiromer (investigational drug) in the treatment of hyperkalemia (high serum potassium). The study also evaluated the effect of withdrawing patiromer treatment and assessed whether chronic treatment with patiromer prevented the recurrence of hyperkalemia. The safety of patiromer treatment was also evaluated.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease (CKD); Hyperkalemia (HK)
• Intervention / Treatment: Drug: Placebo; Drug: Patiromer

Detailed Description

There were two parts in the study, Part A and Part B.

Part A was an assessment of 4 weeks of dosing with patiromer in the treatment of hyperkalemia; Part B was a randomized, placebo-controlled, 8-week assessment of the withdrawal of patiromer in participants with a baseline serum potassium at the beginning of Part A ≥ 5.5 mEq/L who responded to the 4 weeks of treatment with patiromer during Part A.

All participants received patiromer during Part A; Part B participants were randomized to continue patiromer or switch to placebo. Total study participation was up to 14 weeks (including up to 2 weeks of follow up).

The dose of patiromer could be titrated based on participant's serum potassium response.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 3

Contacts and Locations

Study Locations

• Croatia
  • Karlovac, Croatia, 47000
    • Investigator Site 1103
  • Osijek, Croatia, 31000
    • Investigator Site 1102
  • Zagreb, Croatia, 10000
    • Investigator Site 1104
  • Zagreb, Croatia, 10000
    • Investigator Site 1105
  • Zagreb, Croatia, 10000
    • Investigator Site 1106
• Czechia
  • Znojmo, Czechia, 66 902
    • Investigator Site 1205
• Denmark
  • Aarhus N, Denmark, 8200
    • Investigator Site 2103
  • Fredericia, Denmark, 7000
    • Investigator Site 2107
  • Roskilde, Denmark, 4000
    • Investigator Site 2101
  • Viborg, Denmark, 8800
    • Investigator Site 2105
• Georgia
  • Tbilisi, Georgia, 0102
    • Investigator Site 1308
  • Tbilisi, Georgia, 0144
    • Investigator Site 1312
  • Tbilisi, Georgia, 0159
    • Investigator Site 1301
  • Tbilisi, Georgia, 0159
    • Investigator Site 1302
  • Tbilisi, Georgia, 0159
    • Investigator Site 1304
  • Tbilisi, Georgia, 0159
    • Investigator Site 1305
  • Tbilisi, Georgia, 0159
    • Investigator Site 1306
  • Tbilisi, Georgia, 0159
    • Investigator Site 1307
  • Tbilisi, Georgia, 0159
    • Investigator Site 1309
  • Tbilisi, Georgia, 0159
    • Investigator Site 1310
  • Tbilisi, Georgia, 0159
    • Investigator Site 1311
  • Tbilisi, Georgia, 0186
    • Investigator Site 1303
• Hungary
  • Balatonfured, Hungary, H-8230
    • Investigator Site 1410
  • Budapest, Hungary, H-1133
    • Investigator Site 1415
  • Gyor, Hungary, H-9024
    • Investigator Site 1401
  • Hatvan, Hungary, H-3000
    • Investigator Site 1406
  • Jaszbereny, Hungary, H-5100
    • Investigator Site 1405
  • Kistarcsa, Hungary, H-2143
    • Investigator Site 1411
  • Veszprem, Hungary, H-8200
    • Investigator Site 1407
• Italy
  • Pavia, Italy, 27100
    • Investigator Site 2201
• Serbia
  • Belgrade, Serbia, 11000
    • Investigator Site 1703
  • Vrsac, Serbia, 26300
    • Investigator Site 1710
  • Zrenjanin, Serbia, 23000
    • Investigator Site 1707
• Slovenia
  • Celje, Slovenia, 3000
    • Investigator Site 1802
  • Jesenice, Slovenia, 4270
    • Investigator Site 1803
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76018
    • Investigator Site 1915
  • Kharkiv, Ukraine, 61007
    • Investigator Site 1904
  • Kharkiv, Ukraine, 61018
    • Investigator Site 1903
  • Kharkiv, Ukraine, 61039
    • Investigator Site 1908
  • Kyiv, Ukraine, 04114
    • Investigator Site 1909
  • Kyiv, Ukraine, 3680
    • Investigator Site 1911
  • Lugansk, Ukraine, 91045
    • Investigator Site 1914
  • Zaporizhzhia, Ukraine, 69001
    • Investigator Site 1907
  • Zaporizhzhia, Ukraine, 69118
    • Investigator Site 1906
• United States
  • California
    • Azusa, California, United States, 91702
      • Investigator Site 3121
    • Los Angeles, California, United States, 90025
      • Investigator Site 3133
    • Sacramento, California, United States, 95825
      • Investigator Site 3103
    • Santa Barbara, California, United States, 93110
      • Investigator Site 3129
    • Ventura, California, United States, 93003
      • Investigator Site 3130
  • Florida
    • Edgewater, Florida, United States, 32132
      • Investigator Site 3105
    • Hollywood, Florida, United States, 33021
      • Investigator Site 3113
    • Port Charlotte, Florida, United States, 33952
      • Investigator Site 3106
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Investigator Site 3120
  • Missouri
    • Farmington, Missouri, United States, 63640
      • Investigator Site 3102
    • Kansas City, Missouri, United States, 64111
      • Investigator Site 3104
  • New York
    • Flushing, New York, United States, 11355
      • Investigator Site 3134
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Investigator Site 3107
  • Texas
    • San Antonio, Texas, United States, 78229
      • Investigator Site 3110

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females ages 18 - 80
• Chronic kidney disease (CKD) - eGFR 15 to < 60 mL/min/1.73m2 at screening
• Hyperkalemia, defined as a serum potassium value of 5.1 to < 6.5 mEq/L at screening
• Taking either an Angiotensin-Converting Enzyme (ACE) Inhibitor, an Angiotensin II receptor blocker (ARB), or an aldosterone antagonist (AA) medication
• Informed consent given

Exclusion Criteria:

• Participants with auto-immune related chronic kidney disease such as lupus nephritis or renal scleroderma/scleroderma renal crisis, or mixed connective tissue disease with renal involvement
• Participants with uncontrolled Type 1 diabetes, defined as or a HbA1c > 10.0 %, or hospitalization to treat hyper- or hypo-glycemia in the past 3 months within the previous 6 months in participants with Type 2 diabetes
• Participants with severe heart failure, defined as NYHA (New York Heart Association) class IV
• Participants with major surgery including thoracic and cardiac, in the past 3 months, or participants with heart or kidney transplant
• Participants with significant cardiovascular or cerebrovascular events in the past 2 months, such as cardiac arrest, myocardial infarction, or stroke
• Participants with BMI ≥ 40 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patiromer; Patiromer was administered twice a day as a powder mixed with water.	Drug: Patiromer; Other Names: Veltassa; RLY5016 for Oral Suspension
Placebo Comparator: Placebo; Placebo was administered twice a day as a powder mixed with water.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Potassium From Part A Baseline to Part A Week 4	The primary analysis endpoint is the change from Baseline at Week 4. The estimate of the change at Week 4 is from a repeated measures model, which includes data from Weeks 1, 2, 3 and 4. The analysis includes all intent to treat participants who had a serum potassium result at baseline and at least one weekly post-baseline visit (i.e. Part A Week 1 or later) and excludes six participants who had no result collected after Day 3).	Part A Baseline to Part A Week 4
Change in Serum Potassium From Part B Baseline	Change in Serum Potassium from Part B Baseline to either: Part B Week 4 visit, if the participant's serum potassium remained ≥ 3.8 mEq/L and < 5.5 mEq/L up to the Part B Week 4 visit or the earliest Part B visit at which the participant's serum potassium was < 3.8 mEq/L or ≥ 5.5 mEq/L.	Part B Baseline to Part B Week 4 or first local laboratory serum potassium < 3.8 mEq/L or ≥ 5.5 mEq/L

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants With Serum Potassium Levels in the Target Range of 3.8 to < 5.1 mEq/L at Part A Week 4	Week 4
Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B	Part B Baseline to Part B Week 8
Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B	Part B Baseline to Part B Week 8

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.
• Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, Wittes J, Christ-Schmidt H, Berman L, Pitt B; OPAL-HK Investigators. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015 Jan 15;372(3):211-21. doi: 10.1056/NEJMoa1410853. Epub 2014 Nov 21.

Helpful Links

• Relypsa company website

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: March 12, 2013
• First Submitted That Met QC Criteria: March 13, 2013
• First Posted (Estimate): March 14, 2013

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: Chronic Kidney Disease; Treatment of Hyperkalemia; Hyperkalemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Water-Electrolyte Imbalance; Kidney Diseases; Renal Insufficiency, Chronic; Hyperkalemia
• Other Study ID Numbers: RLY5016-301; 2012-001956-20 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No