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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Relypsa, Inc.
ClinicalTrials.gov Identifier:
NCT01371747
First received: June 9, 2011
Last updated: June 17, 2016
Last verified: June 2016
Results First Received: November 11, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Chronic Kidney Disease
Hypertension
Hyperkalemia
Interventions: Drug: patiromer
Drug: losartan
Drug: spironolactone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
324 participants were enrolled in the study; 306 participants were randomized to receive study drug.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening serum potassium ≤ 5 mEq/L (milliequivalent) entered Run-in: Cohort 1 stopped ACEI/ARB (angiotensin-converting enzyme inhibitor/angiotensin receptor blockers), started losartan; Cohort 2 started spironolactone; Run-in (Cohorts 1 and 2) or screening (Cohort 3) > 5 mEq/L entered study.

Reporting Groups
  Description
Stratum 1: 8.4 g/d Patiromer Participants with baseline serum potassium > 5.0 - 5.5 mEq/L randomized to 8.4 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 1: 16.8 g/d Patiromer Participants with baseline serum potassium > 5.0 - 5.5 mEq/L randomized to 16.8 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 1: 25.2 g/d Patiromer Participants with baseline serum potassium > 5.0 - 5.5 mEq/L randomized to 25.2 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 2: 16.8 g/d Patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L randomized to 16.8 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 2: 25.2 g/d Patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L randomized to 25.2 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 2: 33.6 g/d Patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L randomized to 33.6 g/day patiromer starting dose, orally, as a divided dose twice a day.

Participant Flow:   Overall Study
    Stratum 1: 8.4 g/d Patiromer   Stratum 1: 16.8 g/d Patiromer   Stratum 1: 25.2 g/d Patiromer   Stratum 2: 16.8 g/d Patiromer   Stratum 2: 25.2 g/d Patiromer   Stratum 2: 33.6 g/d Patiromer
STARTED   74   74   74   26   28   30 
COMPLETED   56   51   50   17   21   16 
NOT COMPLETED   18   23   24   9   7   14 
Adverse Event                4                2                7                2                2                2 
Death                1                0                4                1                2                0 
Abnormal Renal Function                0                2                0                1                0                1 
High Serum Potassium Results                1                1                1                2                0                2 
Low Serum Potassium Results                1                1                1                1                0                3 
Protocol Violation                0                0                1                0                0                0 
Non-Compliance                3                4                3                0                0                1 
Physician Decision                0                0                0                0                1                0 
Withdrawal by Subject                6                12                5                2                2                4 
Other Reasons                2                1                2                0                0                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
306 participants were randomized and stratified by baseline serum potassium (2 randomized participants in Stratum 1 did not receive any study drug: 1 participant withdrew consent and 1 participant was randomized in error and was withdrawn from the study); 304 participants were analyzed for safety.

Reporting Groups
  Description
Stratum 1: 8.4 g/d Patiromer Participants with baseline serum potassium > 5.0 - 5.5 mEq/L randomized to 8.4 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 1: 16.8 g/d Patiromer Participants with baseline serum potassium > 5.0 - 5.5 mEq/L randomized to 16.8 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 1: 25.2 g/d Patiromer Participants with baseline serum potassium > 5.0 - 5.5 mEq/L randomized to 25.2 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 2: 16.8 g/d Patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L randomized to 16.8 g/day patiromer starting dose, orally, as a divided dose twice a day.
Stratum 2: 25.2 g/d Patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L randomized to 25.2 g/day patiromer starting dose, orally, as a divided dose twice a day
Stratum 2: 33.6 g/d Patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L randomized to 33.6 g/day patiromer starting dose, orally, as a divided dose twice a day.
Total Total of all reporting groups

Baseline Measures
   Stratum 1: 8.4 g/d Patiromer   Stratum 1: 16.8 g/d Patiromer   Stratum 1: 25.2 g/d Patiromer   Stratum 2: 16.8 g/d Patiromer   Stratum 2: 25.2 g/d Patiromer   Stratum 2: 33.6 g/d Patiromer   Total 
Overall Participants Analyzed 
[Units: Participants]
 74   73   73   26   28   30   304 
Age 
[Units: Participants]
             
<=18 years   0   0   0   0   0   0   0 
Between 18 and 65 years   28   29   28   12   12   13   122 
>=65 years   46   44   45   14   16   17   182 
Age 
[Units: Years]
Median (Full Range)
 67 
 (46 to 80) 
 70 
 (37 to 79) 
 68 
 (40 to 79) 
 66.5 
 (56 to 76) 
 68.5 
 (39 to 80) 
 65 
 (44 to 78) 
 67.5 
 (37 to 80) 
Gender 
[Units: Participants]
             
Female   29   26   26   8   13   10   112 
Male   45   47   47   18   15   20   192 


  Outcome Measures
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1.  Primary:   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. ]

2.  Secondary:   Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group   [ Time Frame: Baseline to Week 8 or First Titration which could occur at any scheduled study visit after patiromer initiation. ]

3.  Secondary:   Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group   [ Time Frame: Baseline to Day 3 ]

4.  Secondary:   Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group   [ Time Frame: Baseline to Week 52 ]

5.  Secondary:   Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days   [ Time Frame: Week 52 or Last Patiromer Dose (if Occurred before Week 52) to Following up Visit Plus 7 Days ]

6.  Secondary:   Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group   [ Time Frame: Baseline to Week 8 ]

7.  Secondary:   Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group   [ Time Frame: Baseline to Week 8 ]

8.  Secondary:   Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group   [ Time Frame: Baseline to Week 8 ]

9.  Secondary:   Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group   [ Time Frame: Baseline to Week 52 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Information
Organization: Relypsa, Inc.
phone: 1-844-relypsa
e-mail: medinfo@relypsa.com


Publications:

Responsible Party: Relypsa, Inc.
ClinicalTrials.gov Identifier: NCT01371747     History of Changes
Other Study ID Numbers: RLY5016-205
2011-000165-12 ( EudraCT Number )
Study First Received: June 9, 2011
Results First Received: November 11, 2015
Last Updated: June 17, 2016
Health Authority: Austria: Austrian Federal Office for Safety in Health Care
Croatia: Ministry of Health and Social Welfare of the Republic of Croatia
Georgia: Ministry of Health
Hungary: National Institute of Pharmacy
Serbia: Medicines and Medical Devices Agency of Serbia
Slovenia: Agency for Medicinal products and Medical Devices
Austria: Ethikkommission
Croatia: Ethics Committee
Hungary: Scientific and Medical Research Council Ethics Committee
Serbia: Ethics Committee
Slovenia: Ethics Committee