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

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ClinicalTrials.gov Identifier: NCT01810939
Recruitment Status : Completed
First Posted : March 14, 2013
Results First Posted : December 15, 2015
Last Update Posted : April 11, 2016
Sponsor:
Information provided by (Responsible Party):
Relypsa, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Conditions Chronic Kidney Disease (CKD)
Hyperkalemia (HK)
Interventions Drug: Patiromer
Drug: Placebo
Enrollment 243
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part A Patiromer Part B Patiromer Part B Placebo
Hide Arm/Group Description Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks. Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks. Participants were administered placebo orally twice a day for 8 weeks.
Period Title: Part A Treatment Period
Started 243 0 0
Completed 219 0 0
Not Completed 24 0 0
Reason Not Completed
Non-compliance with Study Drug             1             0             0
Protocol Violation             2             0             0
Adverse Event             10             0             0
Withdrawal by Subject             5             0             0
Protocol-specified (eGFR)             2             0             0
Protocol-specified (High K+)             3             0             0
Protocol-specified (Low K+)             1             0             0
Period Title: Part B Placebo-Controlled Withdrawal
Started 0 55 [1] 52 [1]
Completed 0 45 30
Not Completed 0 10 22
Reason Not Completed
Physician Decision             0             1             1
Non-compliance with Study Drug             0             1             0
Adverse Event             0             1             1
Death             0             0             1
Withdrawal by Subject             0             0             1
Protocol-specified (eGFR)             0             1             1
Protocol-specified (K+ result)             0             1             2
Protocol-specified (High K+)             0             2             14
Protocol-specified (Low K+)             0             2             1
Lost to Follow-up             0             1             0
[1]
Part A participants with Part A baseline serum potassium ≥ 5.5 mEq/L who responded to treatment
Arm/Group Title Part A Patiromer
Hide Arm/Group Description Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
Overall Number of Baseline Participants 243
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 243 participants
<=18 years
0
   0.0%
Between 18 and 65 years
112
  46.1%
>=65 years
131
  53.9%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 243 participants
64.2
(29 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 243 participants
Female
103
  42.4%
Male
140
  57.6%
1.Primary Outcome
Title Change in Serum Potassium From Part A Baseline to Part A Week 4
Hide Description 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).
Time Frame Part A Baseline to Part A Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part A Patiromer
Hide Arm/Group Description:
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks. The dose of patiromer could be titrated based on participant's serum potassium response.
Overall Number of Participants Analyzed 237
Least Squares Mean (Standard Error)
Unit of Measure: mEq/L
-1.01  (0.031)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A Patiromer
Comments Estimation of mean change in serum potassium from Part A Baseline to Part A Week 4 and test mean change different from zero.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Longitudinal mixed models
Comments Test that the mean change is significantly different from zero.
2.Primary Outcome
Title Change in Serum Potassium From Part B Baseline
Hide Description

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.

Time Frame Part B Baseline to Part B Week 4 or first local laboratory serum potassium < 3.8 mEq/L or ≥ 5.5 mEq/L
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part B Placebo Part B Patiromer
Hide Arm/Group Description:
Participants were administered placebo orally twice a day for 8 weeks.
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
Overall Number of Participants Analyzed 52 55
Median (Inter-Quartile Range)
Unit of Measure: mEq/L
0.72
(0.22 to 1.22)
0
(-0.3 to 0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B Placebo, Part B Patiromer
Comments Test for difference between treatment groups in serum potassium change in Part B
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Proportion of Participants With Serum Potassium Levels in the Target Range of 3.8 to < 5.1 mEq/L at Part A Week 4
Hide Description [Not Specified]
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Proportion of participants with serum potassium level in the target range at Part A Week 4
Arm/Group Title Part A Patiromer
Hide Arm/Group Description:
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
Overall Number of Participants Analyzed 243
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
76
(70 to 81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A Patiromer
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Proportion
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.7 to 0.81
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B
Hide Description [Not Specified]
Time Frame Part B Baseline to Part B Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part B Placebo Part B Patiromer
Hide Arm/Group Description:
Participants were administered placebo orally twice a day for 8 weeks.
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
Overall Number of Participants Analyzed 52 55
Measure Type: Number
Unit of Measure: percentage of participants
60 15
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B Placebo, Part B Patiromer
Comments Test for difference between treatment groups in proportion with serum potassium ≥ 5.5 mEq/L
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B
Hide Description [Not Specified]
Time Frame Part B Baseline to Part B Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Percentages were estimated not as simple ratios, but by using a stratified method, in order to account for differences between the patiromer and placebo groups in terms of whether participants had type 2 diabetes mellitus and whether they entered the study with serum potassium < 5.8 mEq/L or serum potassium ≥ 5.8 mEq/L.
Arm/Group Title Part B Placebo Part B Patiromer
Hide Arm/Group Description:
Participants were administered placebo orally twice a day for 8 weeks.
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
Overall Number of Participants Analyzed 52 55
Measure Type: Number
Unit of Measure: percentage of participants
91 43
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B Placebo, Part B Patiromer
Comments Test for difference between treatment groups in proportion with serum potassium ≥ 5.1 mEq/L
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Time Frame 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Adverse Event Reporting Description Participants who received at least one dose of trial medication
 
Arm/Group Title Part A Patiromer Part B Patiromer Part B Placebo
Hide Arm/Group Description Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks. Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks. Participants were administered placebo orally twice a day for 8 weeks.
All-Cause Mortality
Part A Patiromer Part B Patiromer Part B Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part A Patiromer Part B Patiromer Part B Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/243 (1.23%)   0/55 (0.00%)   1/52 (1.92%) 
Cardiac disorders       
Atrial fibrillation  1  1/243 (0.41%)  0/55 (0.00%)  0/52 (0.00%) 
Gastrointestinal disorders       
Thrombosis mesenteric vessel  1  0/243 (0.00%)  0/55 (0.00%)  1/52 (1.92%) 
Infections and infestations       
Escherichia bacteraemia  1  1/243 (0.41%)  0/55 (0.00%)  0/52 (0.00%) 
Urinary tract infection  1  1/243 (0.41%)  0/55 (0.00%)  0/52 (0.00%) 
Endocarditis enterococcal  1  1/243 (0.41%)  0/55 (0.00%)  0/52 (0.00%) 
Investigations       
Anticoagulation drug level below therapeutic  1  1/243 (0.41%)  0/55 (0.00%)  0/52 (0.00%) 
Renal and urinary disorders       
Renal failure chronic  1  1/243 (0.41%)  0/55 (0.00%)  0/52 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A Patiromer Part B Patiromer Part B Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/243 (13.58%)   5/55 (9.09%)   8/52 (15.38%) 
Gastrointestinal disorders       
Constipation  1  26/243 (10.70%)  2/55 (3.64%)  0/52 (0.00%) 
Infections and infestations       
Influenza  1  1/243 (0.41%)  1/55 (1.82%)  3/52 (5.77%) 
Nervous system disorders       
Headache  1  2/243 (0.82%)  2/55 (3.64%)  4/52 (7.69%) 
Vascular disorders       
Hypertension  1  4/243 (1.65%)  0/55 (0.00%)  3/52 (5.77%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreements generally provide that PI cannot publish single site data before publication of the multi-site publication, unless 1 year has elapsed since completion of the study at all sites. Thereafter, PI may publish provided that PI shall: provide a copy of the publication to sponsor at least 60 days in advance of submission for publication; delete sponsor’s confidential information as requested; and delay publication up to an additional 90 days to permit protection of intellectual property.
Results Point of Contact
Name/Title: Medical Information
Organization: Relypsa, Inc.
Phone: 1-844-relypsa
Responsible Party: Relypsa, Inc.
ClinicalTrials.gov Identifier: NCT01810939     History of Changes
Other Study ID Numbers: RLY5016-301
2012-001956-20 ( EudraCT Number )
First Submitted: March 12, 2013
First Posted: March 14, 2013
Results First Submitted: November 11, 2015
Results First Posted: December 15, 2015
Last Update Posted: April 11, 2016