Clinical Trial Results:
A Multicenter, Open-Label, Single-Arm Study to Evaluate a Titration Regimen for RLY5016 in Heart Failure Patients with Chronic Kidney Disease
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Summary
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EudraCT number |
2010-018838-45 |
Trial protocol |
SI |
Global end of trial date |
23 Sep 2010
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Aug 2016
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First version publication date |
06 Aug 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RLY5016–204
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01130597 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Relypsa, Inc.
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Sponsor organisation address |
100 Cardinal Way, Redwood City, United States, 94063
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Public contact |
Medical Information, Relypsa, Inc., medinfo@relypsa.com
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Scientific contact |
Medical Information, Relypsa, Inc., medinfo@relypsa.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Sep 2010
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Sep 2010
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Sep 2010
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of this study was to evaluate the feasibility of individualized titration of patiromer according to serum potassium. This study also assessed the safety and tolerability of patiromer and the effects of patiromer on serum potassium in heart failure (HF) participants with chronic kidney disease (CKD).
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Protection of trial subjects |
This study was conducted in accordance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 May 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Georgia: 45
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Country: Number of subjects enrolled |
Slovenia: 18
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Worldwide total number of subjects |
63
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EEA total number of subjects |
18
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
17
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From 65 to 84 years |
43
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85 years and over |
3
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Recruitment
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Recruitment details |
- | ||||||||||||||||
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Pre-assignment
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Screening details |
Eligible participants were ≥ 18 years old, had a history of chronic HF, were clinically indicated to initiate spironolactone therapy, had a serum potassium measurement of 4.3 – 5.1 mEq/L at screening and baseline, had CKD (eGFR < 60 mL/min/1.73 m2 at screening), and were taking one or more HF therapies (ACEIs, ARBs, or BBs). | ||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Patiromer | ||||||||||||||||
Arm description |
- | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Patiromer
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Investigational medicinal product code |
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Other name |
RLY5016 for Oral Suspension
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Patiromer, 10 g, orally, twice a day for up to 56 days
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Investigational medicinal product name |
Spironolactone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Spironolactone, starting dose of 25 mg, orally, once a day. At clinic visits starting on Day 7 through
Day 49, the dose could be increased once to a maximum of 50 mg/day based on local laboratory serum potassium values; spironolactone dose reductions were not allowed.
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Baseline characteristics reporting groups
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Reporting group title |
Patiromer
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Patiromer
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Reporting group description |
- | ||
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End point title |
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
56 Days
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Because this is a one arm study, the database displayed an error upon validation, prompting for a selection of two arms instead of one. Therefore, the Statistical Analysis was entered as a 95% confidence interval proceeding the outcome data. Clopper-Pearson was used to arrive at this value. |
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| Notes [2] - Clopper-Pearson was used to arrive at the 95% Confidence Interval |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
28 Days
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| Notes [3] - Participants with available data at Week 4. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| Notes [4] - Participants with available data at Week 8. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
28 Days
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| Notes [5] - Participants with available data at Week 4. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| Notes [6] - Participants with available data at Week 8. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| Notes [7] - Clopper-Pearson was used to arrive at the 95% Confidence Interval |
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Dose of Patiromer at End of Treatment | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Requiring Patiromer Uptitration | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Requiring Patiromer Downtitration | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Median Time to First Patiromer Dose Titration | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Number of Patiromer Titrations | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Patiromer Dose at Week 1 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to Week 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Patiromer Dose at Week 4 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to Week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Patiromer Dose at Week 8 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change From Baseline in Serum Potassium to End of Treatment | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
56 Days
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline and Day 28
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| Notes [8] - Participants with urine ACR ≥ 30 mg/g at baseline and available data at Week 4 |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline and Day 56
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| Notes [9] - Participants with urine ACR ≥ 30 mg/g at baseline and available data at Week 8 |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 7 days after Day 56 or last patiromer dose, whichever was earlier.
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Adverse event reporting additional description |
Participants who received at least one dose of trial medication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.0
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Reporting groups
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Reporting group title |
Patiromer
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
