Clinical trial NCT01810939: A Two-Part, Single-Blind, Phase 3 Study Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalemia (OPAL)
Official title: A Two-Part, Single-Blind, Phase 3 Study Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease (CKD)
Hyperkalemia (HK)
Keywords: Chronic Kidney Disease
Treatment of Hyperkalemia
Hyperkalemia
Lead sponsor: Vifor Pharma
Sponsor class: INDUSTRY
First posted: 2013-03-14
Enrollment: 243
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Serum Potassium From Part A Baseline to Part A Week 4
timeFrame: Part A Baseline to Part A Week 4
measure: Change in Serum Potassium From Part B Baseline
timeFrame: Part B Baseline to Part B Week 4 or first local laboratory serum potassium < 3.8 mEq/L or ≥ 5.5 mEq/L
Secondary outcomes:
measure: Proportion of Participants With Serum Potassium Levels in the Target Range of 3.8 to < 5.1 mEq/L at Part A Week 4
timeFrame: Week 4
measure: Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B
timeFrame: Part B Baseline to Part B Week 8
measure: Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B
timeFrame: Part B Baseline to Part B Week 8
Other outcomes:
Locations:
city: Azusa
country: United States
facility: Investigator Site 3121
state: California
city: Los Angeles
country: United States
facility: Investigator Site 3133
state: California
city: Sacramento
country: United States
facility: Investigator Site 3103
state: California
city: Santa Barbara
country: United States
facility: Investigator Site 3129
state: California
city: Ventura
country: United States
facility: Investigator Site 3130
state: California
city: Edgewater
country: United States
facility: Investigator Site 3105
state: Florida
city: Hollywood
country: United States
facility: Investigator Site 3113
state: Florida
city: Port Charlotte
country: United States
facility: Investigator Site 3106
state: Florida
city: Augusta
country: United States
facility: Investigator Site 3120
state: Georgia
city: Farmington
country: United States
facility: Investigator Site 3102
state: Missouri
city: Kansas City
country: United States
facility: Investigator Site 3104
state: Missouri
city: Flushing
country: United States
facility: Investigator Site 3134
state: New York
city: Bethlehem
country: United States
facility: Investigator Site 3107
state: Pennsylvania
city: San Antonio
country: United States
facility: Investigator Site 3110
state: Texas
city: Karlovac
country: Croatia
facility: Investigator Site 1103
city: Osijek
country: Croatia
facility: Investigator Site 1102
city: Zagreb
country: Croatia
facility: Investigator Site 1104
city: Zagreb
country: Croatia
facility: Investigator Site 1105
city: Zagreb
country: Croatia
facility: Investigator Site 1106
city: Znojmo
country: Czechia
facility: Investigator Site 1205
city: Aarhus N
country: Denmark
facility: Investigator Site 2103
city: Fredericia
country: Denmark
facility: Investigator Site 2107
city: Roskilde
country: Denmark
facility: Investigator Site 2101
city: Viborg
country: Denmark
facility: Investigator Site 2105
city: Tbilisi
country: Georgia
facility: Investigator Site 1308
city: Tbilisi
country: Georgia
facility: Investigator Site 1312
city: Tbilisi
country: Georgia
facility: Investigator Site 1301
city: Tbilisi
country: Georgia
facility: Investigator Site 1302
city: Tbilisi
country: Georgia
facility: Investigator Site 1304
city: Tbilisi
country: Georgia
facility: Investigator Site 1305
city: Tbilisi
country: Georgia
facility: Investigator Site 1306
city: Tbilisi
country: Georgia
facility: Investigator Site 1307
city: Tbilisi
country: Georgia
facility: Investigator Site 1309
city: Tbilisi
country: Georgia
facility: Investigator Site 1310
city: Tbilisi
country: Georgia
facility: Investigator Site 1311
city: Tbilisi
country: Georgia
facility: Investigator Site 1303
city: Balatonfured
country: Hungary
facility: Investigator Site 1410
city: Budapest
country: Hungary
facility: Investigator Site 1415
city: Gyor
country: Hungary
facility: Investigator Site 1401
city: Hatvan
country: Hungary
facility: Investigator Site 1406
city: Jaszbereny
country: Hungary
facility: Investigator Site 1405
city: Kistarcsa
country: Hungary
facility: Investigator Site 1411
city: Veszprem
country: Hungary
facility: Investigator Site 1407
city: Pavia
country: Italy
facility: Investigator Site 2201
city: Belgrade
country: Serbia
facility: Investigator Site 1703
city: Vrsac
country: Serbia
facility: Investigator Site 1710
city: Zrenjanin
country: Serbia
facility: Investigator Site 1707
city: Celje
country: Slovenia
facility: Investigator Site 1802
city: Jesenice
country: Slovenia
facility: Investigator Site 1803
city: Ivano-Frankivsk
country: Ukraine
facility: Investigator Site 1915
city: Kharkiv
country: Ukraine
facility: Investigator Site 1904
city: Kharkiv
country: Ukraine
facility: Investigator Site 1903
city: Kharkiv
country: Ukraine
facility: Investigator Site 1908
city: Kyiv
country: Ukraine
facility: Investigator Site 1909
city: Kyiv
country: Ukraine
facility: Investigator Site 1911
city: Lugansk
country: Ukraine
facility: Investigator Site 1914
city: Zaporizhzhia
country: Ukraine
facility: Investigator Site 1907
city: Zaporizhzhia
country: Ukraine
facility: Investigator Site 1906
Study officials:
affiliation: Relypsa, Inc.
name: Director Clinical Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.