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

Phase 3

Completed

• Conditions: Hyperkalemia (HK); Chronic Kidney Disease (CKD)
• Interventions: Drug: Placebo; Drug: Patiromer

• Registration Number: NCT01810939
• Lead Sponsor: Relypsa, Inc.

Brief Summary

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.

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 Timeline

• Study Start: 2013-02
• Study First Submitted: 2013-03-12
• Study First Submitted QC: 2013-03-13
• Study First Posted: 2013-03-14
• Primary Completion: 2013-07
• Study Completion: 2013-08
• Disposition First Submitted: 2014-10-29
• Disposition First Submitted QC: 2014-10-29
• Disposition First Posted: 2014-11-05
• Results First Submitted: 2015-11-11
• Results First Submitted QC: 2015-11-11
• Results First Posted: 2015-12-15
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-10
• Last Update Posted: 2021-06-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 243

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo was administered twice a day as a powder mixed with water.
Patiromer	Patiromer	Patiromer was administered twice a day as a powder mixed with water.

Primary Outcome Measures

Name	Time	Method
Change in Serum Potassium From Part A Baseline to Part A Week 4	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).
Change in Serum Potassium From Part B Baseline	Part B Baseline to Part B Week 4 or first local laboratory serum potassium < 3.8 mEq/L or ≥ 5.5 mEq/L	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.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (58)

Investigator Site 3121; 🇺🇸 Azusa, California, United States

Investigator Site 3133; 🇺🇸 Los Angeles, California, United States

Investigator Site 3103; 🇺🇸 Sacramento, California, United States

Investigator Site 3129; 🇺🇸 Santa Barbara, California, United States

Investigator Site 3130; 🇺🇸 Ventura, California, United States

Investigator Site 3105; 🇺🇸 Edgewater, Florida, United States

Investigator Site 3113; 🇺🇸 Hollywood, Florida, United States

Investigator Site 3106; 🇺🇸 Port Charlotte, Florida, United States

Investigator Site 3120; 🇺🇸 Augusta, Georgia, United States

Investigator Site 3102; 🇺🇸 Farmington, Missouri, United States

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