AMBER: Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease
Sponsor
Relypsa, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03071263
Collaborator
(none)
295
40
2
22.1
7.4
0.3
Study Details
Study Description
Brief Summary
The purpose of this study is to determine if patiromer treatment in chronic kidney disease (CKD) subjects receiving spironolactone for the treatment of resistant hypertension will result in more persistent use of spironolactone through prevention of hyperkalemia and lead to improved blood pressure control compared with treatment with spironolactone alone (placebo).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Approximately 290 eligible participants with [chronic kidney disease (CKD) on stable doses of medication] will be randomly assigned to receive a patiromer or placebo starting dose of two packets a day, once a day.
All eligible participants will undergo a screening/run-in period (up to 4 weeks) to determine eligibility for study entry. Eligible participants will be randomized and treated for 12 weeks (Treatment Period) and followed for 2 weeks after completing the patiromer or placebo treatment. There are 8 planned clinic visits during the Treatment Period and one planned visit two weeks after the last dose of patiromer or placebo (Follow-up Period).
The dose of patiromer or placebo may be increased or decreased (titrated) based on participants' individual potassium response.
Study Design
Study Type:
Interventional
Actual Enrollment
:
295 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo Controlled, Parallel Group Study of Patiromer for the Enablement of Spironolactone Use for Blood Pressure Control in Patients With Resistant Hypertension and Chronic Kidney Disease
Actual Study Start Date
:
Jan 23, 2017
Actual Primary Completion Date
:
Nov 27, 2018
Actual Study Completion Date
:
Nov 27, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group 1 - Patiromer spironolactone + blinded patiromer |
Drug: Patiromer
2 packets/day starting dose, administered orally
Other Names:
Drug: Spironolactone
25 mg tablet/day starting dose, administered orally
|
| Experimental: Group 2 - Placebo spironolactone + blinded placebo |
Drug: Placebo
2 packets/day starting dose, administered orally
Drug: Spironolactone
25 mg tablet/day starting dose, administered orally
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Remaining on Spironolactone at Week 12 [At week 12]
The proportion of subjects remaining on spironolactone at Week 12 will be compared between treatment groups (spironolactone/patiromer versus spironolactone/placebo). Subjects who discontinued from the study early or discontinued study spironolactone prior to Week 12, for any reason, were considered as not having remained on spironolactone until Week 12.
Secondary Outcome Measures
- Change in AOBP SBP From Baseline to Week 12 or Last Available AOBP SBP Prior to Addition of Any New BP Medications or Increase From Any Baseline BP Medications [From baseline to Week 12]
AOBP: Automated Office Blood Pressure SBP: Systolic Blood Pressure BP: Blood Pressure
Other Outcome Measures
- Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives [From baseline to Week 12]
AOBP SBP: Automated Office Systolic Blood Pressure
- Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category [From baseline to Week 12]
The two baseline potassium subgroups, 4.3-<4.7 mEq/L versus 4.7-5.1 mEq/L, are based on central laboratory data. If a participant's serum potassium result at baseline was not in one of the two subgroups reported below, the participant's potassium stratum at randomization was used. Therefore, participants with BCSP <4.3 mEq/L or >5.1 mEq/L at baseline (Day 0) have been classified according to their serum potassium values at the Screening period.
- Participants With Central Serum Potassium <5.5 mEq/L Over Time [From baseline to Week 12]
Baseline Central Serum Potassium: BCSP. The symbols > and ≤ included in the row titles are used to indicate the time interval [">Week1 and ≤Week2" meaning from day 8 until day 14 (included)]. If a participant's serum potassium result at baseline was not in one of the two subgroups reported below, the participant's potassium stratum at randomization was used. Therefore, participants with BCSP <4.3 mEq/L or >5.1 mEq/L at baseline (Day 0) have been classified according to their serum potassium values at the Screening period.
- Participants Having Spironolactone Titrations Over Time [From baseline to Week 12]
The titration was performed according to the following criteria: Spironolactone was increased in cases of hypertension, decreased or stopped in cases of hypotension and maintained if the blood pressure results were adequate The symbols > and ≤ included in the row titles are used to indicate the time interval [">Week1 and ≤Week2" meaning from day 8 until day 14 (included)].
- Number of Participants by Spironolactone Dose Prescribed at Each Visit [From baseline to Week 10]
QD: Once daily QOD: Once every other day
- Shifts in Selected Laboratory Tests From Baseline to End of Treatment [From Baseline to End of Treatment, up to 12 weeks.]
The end of treatment value is defined as the last non-missing value on or prior to the last spironolactone dose date (from End of Treatment - Case report form) + 3 days LLN=Lower limit of the normal range. ULN=Upper limit of the normal range. EoT=End of Treatment
- Spironolactone Dose Level at End of 12 Weeks of Study Treatment [12 Weeks of Study Treatment]
Row title: Participants not completing 12W of study treatment: Participants who had not completed 12 weeks of study treatment.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age ≥ 18 years
-
Taking at least three medications for blood pressure (one a diuretic)
-
Uncontrolled high blood pressure
-
Abnormal kidney function (with-eGFR, a measure of kidney function, of 25 - ≤ 45 mL/min/1.73m2
-
Normal Blood serum Potassium in a specific range (4.3 - 5.1 mEq/L)
Exclusion Criteria:
-
History of untreated known causes of high blood pressure, excluding kidney disease (not CKD)
-
Inability to measure BP
-
Not taking high blood pressure medications as prescribed medications
-
Recent change in renal function (in the past 3 months) which has required hospitalization or dialysis
-
Renal transplant
-
History of cancer within past 12 months
-
Recent cardiovascular event with last 3 months
-
Clinically significant abnormalities of heart rhythm (ventricular arrhythmia or atrial fibrillation with uncontrolled heart rate)
-
Inability to take study medication
-
Alcoholism
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigator Site 1012 | Hollywood | Florida | United States | 33021 |
| 2 | Investigator Site 1023 | Miami Lakes | Florida | United States | 33014 |
| 3 | Investigator Site 1022 | Chicago | Illinois | United States | 60611 |
| 4 | Investigator Site 1402 | Sofia | Bulgaria | 1612 | |
| 5 | Investiagor Site 2205 | Zagreb | Croatia | 10000 | |
| 6 | Investigator Site 2201 | Zagreb | Croatia | 10000 | |
| 7 | Investigator Site 2202 | Zagreb | Croatia | 10000 | |
| 8 | Investigator Site 2203 | Zagreb | Croatia | 10000 | |
| 9 | Investigator Site 3806 | Tbilisi | Georgia | 0102 | |
| 10 | Investigator Site 3811 | Tbilisi | Georgia | 0112 | |
| 11 | Investigator Site 3802 | Tbilisi | Georgia | 0144 | |
| 12 | Investigator Site 3801 | Tbilisi | Georgia | 0159 | |
| 13 | Investigator Site 3804 | Tbilisi | Georgia | 0159 | |
| 14 | Investigator Site 3805 | Tbilisi | Georgia | 0159 | |
| 15 | Investigator Site 3807 | Tbilisi | Georgia | 0159 | |
| 16 | Investigator Site 3808 | Tbilisi | Georgia | 0159 | |
| 17 | Investigator Site 3810 | Tbilisi | Georgia | 0159 | |
| 18 | Investigator Site 3812 | Tbilisi | Georgia | 0159 | |
| 19 | Investigator Site 3813 | Tbilisi | Georgia | 0159 | |
| 20 | Investigator Site 3809 | Tbilisi | Georgia | 0186 | |
| 21 | Investigator Site 4202 | Gottingen | Germany | 37075 | |
| 22 | Investigator Site 4607 | Balatonfured | Hungary | H-8230 | |
| 23 | Investigator Site 4606 | Budapest | Hungary | H-1097 | |
| 24 | Investigator Site 4611 | Debrecen | Hungary | 4032 | |
| 25 | Investigator Site 4601 | Hatvan | Hungary | H-3000 | |
| 26 | Investigator Site 4605 | Kistarcsa | Hungary | H-2143 | |
| 27 | Investigator Site 4602 | Miskolc | Hungary | H-3529 | |
| 28 | Investigator Site 4610 | Miskolc | Hungary | H-3530 | |
| 29 | Investigator Site 4608 | Mosonmagyarovar | Hungary | H-9200 | |
| 30 | Investigator Site 7403 | Johannesburg | South Africa | ||
| 31 | Investigator Site 7803 | Khar'kov | Ukraine | 61006 | |
| 32 | Investiagor Site 7809 | Kharkiv | Ukraine | 61002 | |
| 33 | Investigator Site 7808 | Kharkiv | Ukraine | 61039 | |
| 34 | Investigator Site 7802 | Kharkiv | Ukraine | 61103 | |
| 35 | Investigator Site 7805 | Kiev | Ukraine | 03680 | |
| 36 | Investigator Site 7801 | Kiev | Ukraine | 04114 | |
| 37 | Investigator Site 7804 | Zaporizhzhia | Ukraine | 69001 | |
| 38 | Investigator Site 7807 | Zaporizhzhia | Ukraine | 69118 | |
| 39 | Investigator Site 8202 | Leicester | United Kingdom | LE5 4QF | |
| 40 | Investigator Site 8205 | London | United Kingdom | Se5 9RS |
Sponsors and Collaborators
- Relypsa, Inc.
Investigators
- Study Director: Study Director or VP Clinical Development, Relypsa, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Relypsa, Inc.
ClinicalTrials.gov Identifier:
NCT03071263
Other Study ID Numbers:
- RLY5016-207
- 2016-002657-38
First Posted:
Mar 6, 2017
Last Update Posted:
May 12, 2021
Last Verified:
May 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Relypsa, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Period Title: Overall Study | ||
| STARTED | 147 | 148 |
| COMPLETED | 144 | 141 |
| NOT COMPLETED | 3 | 7 |
Baseline Characteristics
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Total of all reporting groups |
| Overall Participants | 147 | 148 | 295 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
49
33.3%
|
44
29.7%
|
93
31.5%
|
| >=65 years |
98
66.7%
|
104
70.3%
|
202
68.5%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
67.8
(12.24)
|
68.5
(11.13)
|
68.1
(11.69)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
71
48.3%
|
71
48%
|
142
48.1%
|
| Male |
76
51.7%
|
77
52%
|
153
51.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
7
4.8%
|
16
10.8%
|
23
7.8%
|
| Not Hispanic or Latino |
140
95.2%
|
131
88.5%
|
271
91.9%
|
| Unknown or Not Reported |
0
0%
|
1
0.7%
|
1
0.3%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
1.4%
|
2
1.4%
|
4
1.4%
|
| White |
145
98.6%
|
145
98%
|
290
98.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
0.7%
|
1
0.3%
|
| Baseline central laboratory serum potassium (Count of Participants) | |||
| Baseline serum potassium <4.3 mEq/L |
7
4.8%
|
17
11.5%
|
24
8.1%
|
| Baseline serum potassium 4.3-<4.7 mEq/L |
55
37.4%
|
52
35.1%
|
107
36.3%
|
| Baseline serum potassium 4.7-5.1 mEq/L |
65
44.2%
|
65
43.9%
|
130
44.1%
|
| Baseline serum potassium >5.1 mEq/L |
20
13.6%
|
14
9.5%
|
34
11.5%
|
| Baseline eGFR (mL/min/1.73m^2) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mL/min/1.73m^2] |
35.37
(7.274)
|
36.08
(7.597)
|
35.73
(7.434)
|
| Systolic blood pressure as measured using automated office blood pressure device (AOBP SBP) (mmHg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mmHg] |
143.3
(6.48)
|
144.9
(7.01)
|
144.1
(6.79)
|
| Antihypertensive Medications at Baseline (Count of Participants) | |||
| Perindopril |
54
36.7%
|
51
34.5%
|
105
35.6%
|
| Valsartan |
38
25.9%
|
27
18.2%
|
65
22%
|
| Losartan |
20
13.6%
|
26
17.6%
|
46
15.6%
|
| Indapamide |
62
42.2%
|
58
39.2%
|
120
40.7%
|
| Hydrochlorothiazide |
52
35.4%
|
60
40.5%
|
112
38%
|
| Furosemide |
26
17.7%
|
17
11.5%
|
43
14.6%
|
| Torasemide |
15
10.2%
|
17
11.5%
|
32
10.8%
|
| Amlodipine |
74
50.3%
|
86
58.1%
|
160
54.2%
|
| Lercanidipine |
18
12.2%
|
15
10.1%
|
33
11.2%
|
| Bisoprolol |
34
23.1%
|
43
29.1%
|
77
26.1%
|
| Nebivolol |
26
17.7%
|
19
12.8%
|
45
15.3%
|
| Other antihypertensives |
40
27.2%
|
31
20.9%
|
71
24.1%
|
Outcome Measures
| Title | Number of Participants Remaining on Spironolactone at Week 12 |
|---|---|
| Description | The proportion of subjects remaining on spironolactone at Week 12 will be compared between treatment groups (spironolactone/patiromer versus spironolactone/placebo). Subjects who discontinued from the study early or discontinued study spironolactone prior to Week 12, for any reason, were considered as not having remained on spironolactone until Week 12. |
| Time Frame | At week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 147 | 148 |
| Count of Participants [Participants] |
126
85.7%
|
98
66.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1 - Patiromer, Group 2 - Placebo |
|---|---|---|
| Comments | A sample size of 280 subjects has 90% power to detect a difference between treatment groups of 20% or more in the proportion of subjects remaining on spironolactone at Week 12, at α = 0.05. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | α-level 0.05. Stratified by baseline potassium category (4.3-<4.7 mEq/L or 4.7-5.1 mEq/L) and history of Type 1 or Type 2 diabetes mellitus (Yes or No) as randomized | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Change in AOBP SBP From Baseline to Week 12 or Last Available AOBP SBP Prior to Addition of Any New BP Medications or Increase From Any Baseline BP Medications |
|---|---|
| Description | AOBP: Automated Office Blood Pressure SBP: Systolic Blood Pressure BP: Blood Pressure |
| Time Frame | From baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 144 | 141 |
| Mean (Standard Deviation) [mmHg] |
-11.3
(14.11)
|
-11.0
(15.34)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1 - Patiromer, Group 2 - Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5757 |
| Comments | Baseline AOBP SBP as a covariate and treatment group, baseline serum potassium (K+ 4.3-<4.7 or 4.7-5.1 mEq/L), and history of Type 1 or Type 2 diabetes mellitus (Yes or No) as factors in the model. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives |
|---|---|
| Description | AOBP SBP: Automated Office Systolic Blood Pressure |
| Time Frame | From baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 144 | 141 |
| Mean (Standard Deviation) [mmHg] |
-11.3
(14.11)
|
-11.2
(15.04)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1 - Patiromer, Group 2 - Placebo |
|---|---|---|
| Comments | The p-value is from a test comparing the difference between two groups in the mean change in AOBP SBP from baseline. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6367 |
| Comments | Baseline AOBP SBP as a covariate and treatment group, baseline serum potassium (K+ 4.3-<4.7 or 4.7-5.1 mEq/L), and history of Type 1 or Type 2 diabetes mellitus as factors in the model. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category |
|---|---|
| Description | The two baseline potassium subgroups, 4.3-<4.7 mEq/L versus 4.7-5.1 mEq/L, are based on central laboratory data. If a participant's serum potassium result at baseline was not in one of the two subgroups reported below, the participant's potassium stratum at randomization was used. Therefore, participants with BCSP <4.3 mEq/L or >5.1 mEq/L at baseline (Day 0) have been classified according to their serum potassium values at the Screening period. |
| Time Frame | From baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. Table depicts those participants with values at Baseline and Week 12. Those participants with no available results at W12 were not included in the table below. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 144 | 140 |
| Baseline Central Serum Potassium 4.3-<4.7 mEq/L |
0.16
(0.468)
|
0.40
(0.494)
|
| Baseline Central Serum Potassium 4.7-<5.1 mEq/L |
-0.09
(0.442)
|
0.03
(0.468)
|
| Overall |
0.02
(0.469)
|
0.20
(0.514)
|
| Title | Participants With Central Serum Potassium <5.5 mEq/L Over Time |
|---|---|
| Description | Baseline Central Serum Potassium: BCSP. The symbols > and ≤ included in the row titles are used to indicate the time interval [">Week1 and ≤Week2" meaning from day 8 until day 14 (included)]. If a participant's serum potassium result at baseline was not in one of the two subgroups reported below, the participant's potassium stratum at randomization was used. Therefore, participants with BCSP <4.3 mEq/L or >5.1 mEq/L at baseline (Day 0) have been classified according to their serum potassium values at the Screening period. |
| Time Frame | From baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. Table depicts those participants with values at mentioned time frame. Those participants with no available results were not included in the table below. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 147 | 148 |
| BCSP 4.3-<4.7mEq/L: ≤Week1 |
60
40.8%
|
62
41.9%
|
| BCSP 4.3-<4.7mEq/L: >Week1 and ≤Week2 |
57
38.8%
|
57
38.5%
|
| BCSP 4.3-<4.7mEq/L: >Week 2 and ≤Week 3 |
59
40.1%
|
63
42.6%
|
| BCSP 4.3-<4.7mEq/L: >Week 3 and ≤Week 4 |
61
41.5%
|
60
40.5%
|
| BCSP 4.3-<4.7mEq/L: >Week 4 and ≤Week 6 |
61
41.5%
|
61
41.2%
|
| BCSP 4.3-<4.7mEq/L: >Week 6 and ≤Week 8 |
61
41.5%
|
58
39.2%
|
| BCSP 4.3-<4.7mEq/L: >Week 8 and ≤Week 10 |
58
39.5%
|
58
39.2%
|
| BCSP 4.3-<4.7mEq/L: > Week 10 and ≤ Week 12 |
61
41.5%
|
61
41.2%
|
| BCSP 4.7-<5.1 mEq/L: ≤Week 1 |
75
51%
|
66
44.6%
|
| BCSP 4.7-<5.1mEq/L: >Week 1 and ≤Week 2 |
74
50.3%
|
65
43.9%
|
| BCSP 4.7-<5.1mEq/L: >Week 2 and ≤Week 3 |
74
50.3%
|
65
43.9%
|
| BCSP 4.7-<5.1mEq/L: >Week 3 and ≤Week 4 |
74
50.3%
|
61
41.2%
|
| BCSP 4.7-<5.1 mEq/L: >Week 4 and ≤Week 6 |
79
53.7%
|
64
43.2%
|
| BCSP 4.7-<5.1mEq/L: >Week 6 and ≤Week 8 |
74
50.3%
|
66
44.6%
|
| BCSP 4.7-<5.1mEq/L: >Week 8 and ≤Week 10 |
72
49%
|
66
44.6%
|
| BCSP 4.7-<5.1mEq/L: >Week 10 and ≤Week 12 |
80
54.4%
|
65
43.9%
|
| Overall : ≤Week 1 |
135
91.8%
|
128
86.5%
|
| Overall : > Week 1 and ≤Week 2 |
131
89.1%
|
122
82.4%
|
| Overall : >Week 2 and ≤Week 3 |
133
90.5%
|
128
86.5%
|
| Overall : >Week 3 and ≤Week 4 |
135
91.8%
|
121
81.8%
|
| Overall : >Week 4 and ≤Week 6 |
140
95.2%
|
125
84.5%
|
| Overall : >Week 6 and ≤Week 8 |
135
91.8%
|
124
83.8%
|
| Overall : >Week 8 and ≤Week 10 |
130
88.4%
|
124
83.8%
|
| Overall : >Week 10 and ≤Week 12 |
141
95.9%
|
126
85.1%
|
| Title | Participants Having Spironolactone Titrations Over Time |
|---|---|
| Description | The titration was performed according to the following criteria: Spironolactone was increased in cases of hypertension, decreased or stopped in cases of hypotension and maintained if the blood pressure results were adequate The symbols > and ≤ included in the row titles are used to indicate the time interval [">Week1 and ≤Week2" meaning from day 8 until day 14 (included)]. |
| Time Frame | From baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. Reported results only include the number of participants having spironolactone titrations over time according to the classification defined below. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 147 | 148 |
| Up : ≤Week 1 |
0
0%
|
0
0%
|
| Up : >Week 1 and ≤Week 2 |
0
0%
|
0
0%
|
| Up : >Week 2 and ≤Week 3 |
88
59.9%
|
77
52%
|
| Up : >Week 3 and ≤Week 4 |
27
18.4%
|
21
14.2%
|
| Up : >Week 4 and ≤Week 6 |
10
6.8%
|
11
7.4%
|
| Up : >Week 6 and ≤Week 8 |
6
4.1%
|
6
4.1%
|
| Up : >Week 8 and ≤Week 10 |
6
4.1%
|
7
4.7%
|
| Up : >Week 10 and ≤Week 12 |
1
0.7%
|
0
0%
|
| Down : ≤Week 1 |
1
0.7%
|
2
1.4%
|
| Down : >Week 1 and ≤Week 2 |
2
1.4%
|
0
0%
|
| Down : >Week 2 and ≤Week 3 |
2
1.4%
|
2
1.4%
|
| Down : >Week 3 and ≤Week 4 |
6
4.1%
|
5
3.4%
|
| Down : >Week 4 and ≤Week 6 |
8
5.4%
|
7
4.7%
|
| Down : >Week 6 and ≤Week 8 |
5
3.4%
|
8
5.4%
|
| Down : >Week 8 and ≤Week 10 |
4
2.7%
|
7
4.7%
|
| Down : >Week 10 and ≤Week 12 |
3
2%
|
1
0.7%
|
| Title | Number of Participants by Spironolactone Dose Prescribed at Each Visit |
|---|---|
| Description | QD: Once daily QOD: Once every other day |
| Time Frame | From baseline to Week 10 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 147 | 148 |
| 50 mg QD : Baseline |
0
0%
|
0
0%
|
| 50 mg QD : Week 1 |
0
0%
|
0
0%
|
| 50 mg QD : Week 2 |
0
0%
|
0
0%
|
| 50 mg QD : Week 3 |
86
58.5%
|
76
51.4%
|
| 50 mg QD : Week 4 |
105
71.4%
|
94
63.5%
|
| 50 mg QD : Week 6 |
106
72.1%
|
96
64.9%
|
| 50 mg QD : Week 8 |
106
72.1%
|
85
57.4%
|
| 50 mg QD : Week 10 |
106
72.1%
|
80
54.1%
|
| 25 mg QD : Baseline |
147
100%
|
148
100%
|
| 25 mg QD : Week 1 |
145
98.6%
|
144
97.3%
|
| 25 mg QD : Week 2 |
140
95.2%
|
142
95.9%
|
| 25 mg QD : Week 3 |
49
33.3%
|
57
38.5%
|
| 25 mg QD : Week 4 |
27
18.4%
|
34
23%
|
| 25 mg QD : Week 6 |
25
17%
|
28
18.9%
|
| 25 mg QD : Week 8 |
26
17.7%
|
24
16.2%
|
| 25 mg QD : Week 10 |
19
12.9%
|
20
13.5%
|
| 25 mg QOD : Baseline |
0
0%
|
0
0%
|
| 25 mg QOD : Week 1 |
1
0.7%
|
2
1.4%
|
| 25 mg QOD : Week 2 |
3
2%
|
1
0.7%
|
| 25 mg QOD : Week 3 |
3
2%
|
2
1.4%
|
| 25 mg QOD : Week 4 |
3
2%
|
3
2%
|
| 25 mg QOD : Week 6 |
2
1.4%
|
2
1.4%
|
| 25 mg QOD : Week 8 |
1
0.7%
|
4
2.7%
|
| 25 mg QOD : Week 10 |
2
1.4%
|
4
2.7%
|
| Title | Shifts in Selected Laboratory Tests From Baseline to End of Treatment |
|---|---|
| Description | The end of treatment value is defined as the last non-missing value on or prior to the last spironolactone dose date (from End of Treatment - Case report form) + 3 days LLN=Lower limit of the normal range. ULN=Upper limit of the normal range. EoT=End of Treatment |
| Time Frame | From Baseline to End of Treatment, up to 12 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 146 | 147 |
| Magnesium - Baseline Value <LLN : EoT Value<LLN |
9
6.1%
|
4
2.7%
|
| Magnesium - Baseline Value <LLN : EoT Value Normal |
3
2%
|
8
5.4%
|
| Magnesium - Baseline Value <LLN : EoT Value >ULN |
0
0%
|
0
0%
|
| Magnesium - Baseline Value Normal : EoT Value <LLN |
12
8.2%
|
7
4.7%
|
| Magnesium- Baseline Value Normal: EoT Value Normal |
103
70.1%
|
109
73.6%
|
| Magnesium - Baseline Value Normal : EoT Value >ULN |
6
4.1%
|
10
6.8%
|
| Magnesium - Baseline Value >ULN : EoT Value <LLN |
0
0%
|
0
0%
|
| Magnesium - Baseline Value >ULN : EoT Value Normal |
10
6.8%
|
6
4.1%
|
| Magnesium - Baseline Value >ULN : EoT Value >ULN |
3
2%
|
3
2%
|
| Phosphate - Baseline Value <LLN : EoT Value <LLN |
0
0%
|
1
0.7%
|
| Phosphate - Baseline Value <LLN : EoT Value Normal |
1
0.7%
|
3
2%
|
| Phosphate - Baseline Value <LLN : EoT Value >ULN |
0
0%
|
0
0%
|
| Phosphate - Baseline Value Normal : EoT Value <LLN |
0
0%
|
1
0.7%
|
| Phosphate- Baseline Value Normal: EoT Value Normal |
136
92.5%
|
125
84.5%
|
| Phosphate - Baseline Value Normal : EoT Value >ULN |
2
1.4%
|
8
5.4%
|
| Phosphate - Baseline Value >ULN : EoT Value <LLN |
0
0%
|
0
0%
|
| Phosphate - Baseline Value >ULN : EoT Value Normal |
5
3.4%
|
4
2.7%
|
| Phosphate - Baseline Value >ULN : EoT Value >ULN |
2
1.4%
|
5
3.4%
|
| Calcium - Baseline Value <LLN : EoT Value <LLN |
2
1.4%
|
4
2.7%
|
| Calcium - Baseline Value <LLN : EoT Value Normal |
5
3.4%
|
1
0.7%
|
| Calcium - Baseline Value <LLN : EoT Value >ULN |
0
0%
|
0
0%
|
| Calcium - Baseline Value Normal : EoT Value <LLN |
4
2.7%
|
6
4.1%
|
| Calcium - Baseline Value Normal : EoT Value Normal |
133
90.5%
|
133
89.9%
|
| Calcium - Baseline Value Normal : EoT Value >ULN |
0
0%
|
0
0%
|
| Calcium - Baseline Value >ULN : EoT Value <LLN |
0
0%
|
0
0%
|
| Calcium - Baseline Value >ULN : EoT Value Normal |
2
1.4%
|
1
0.7%
|
| Calcium - Baseline Value >ULN : EoT Value >ULN |
0
0%
|
2
1.4%
|
| Title | Spironolactone Dose Level at End of 12 Weeks of Study Treatment |
|---|---|
| Description | Row title: Participants not completing 12W of study treatment: Participants who had not completed 12 weeks of study treatment. |
| Time Frame | 12 Weeks of Study Treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 147 | 148 |
| 50 mg QD |
102
69.4%
|
76
51.4%
|
| 25 mg QD |
22
15%
|
19
12.8%
|
| 25 mg QOD |
2
1.4%
|
3
2%
|
| Participants not completing 12W of study treatment |
21
14.3%
|
50
33.8%
|
| Title | Number of Participants Requiring Additional New Antihypertensive Medications or Increases to Baseline Antihypertensive Medications |
|---|---|
| Description | Row Titles: AM: Antihypertensive Medication(s) New AM: Participants who required additional new antihypertensive medication(s) Increases to baseline AM: Participants who required increases to baseline antihypertensive medication(s) Addition new (or increase) AM: Participants who required addition of new antihypertensive medication(s) and/or increases to baseline antihypertensive medications At any time during the study: During study While on study medication: On medication |
| Time Frame | From baseline to Week 12/Early Termination visit |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (ITT): The ITT population included all participants who were randomized and who took at least 1 dose of spironolactone and at least 1 dose of patiromer/placebo. |
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo |
|---|---|---|
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally |
| Measure Participants | 147 | 148 |
| New AM : At any time during the study |
0
0%
|
3
2%
|
| New AM : On medication |
0
0%
|
1
0.7%
|
| Increases to baseline AM: During study |
0
0%
|
2
1.4%
|
| Increases to baseline AM: On medication |
0
0%
|
1
0.7%
|
| Addition new (or increases) AM: During study |
0
0%
|
4
2.7%
|
| Addition new (or increases) AM : On medication |
0
0%
|
2
1.4%
|
Adverse Events
| Time Frame | During Treatment Period (12 weeks); until Follow-up Visit 2 weeks after the Week 12 Visit (or Early Termination Visit). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Group 1 - Patiromer | Group 2 - Placebo | ||
| Arm/Group Description | Spironolactone + blinded patiromer Patiromer: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | Spironolactone + blinded placebo Placebo: 2 packets/day starting dose, administered orally Spironolactone: 25 mg tablet/day starting dose, administered orally | ||
All Cause Mortality |
||||
| Group 1 - Patiromer | Group 2 - Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/147 (0%) | 1/148 (0.7%) | ||
Serious Adverse Events |
||||
| Group 1 - Patiromer | Group 2 - Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/147 (0.7%) | 4/148 (2.7%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 0/147 (0%) | 1/148 (0.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Humerus fracture | 1/147 (0.7%) | 0/148 (0%) | ||
| Renal and urinary disorders | ||||
| Renal failure | 0/147 (0%) | 1/148 (0.7%) | ||
| Renal colic | 0/147 (0%) | 1/148 (0.7%) | ||
| Vascular disorders | ||||
| Aortic rupture | 0/147 (0%) | 1/148 (0.7%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Group 1 - Patiromer | Group 2 - Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/147 (32%) | 48/148 (32.4%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 9/147 (6.1%) | 8/148 (5.4%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperkalaemia | 7/147 (4.8%) | 13/148 (8.8%) | ||
| Nervous system disorders | ||||
| Headache | 9/147 (6.1%) | 11/148 (7.4%) | ||
| Renal and urinary disorders | ||||
| Renal impairment | 13/147 (8.8%) | 10/148 (6.8%) | ||
| Vascular disorders | ||||
| Hypotension | 9/147 (6.1%) | 6/148 (4.1%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
No Confidential Information will be disclosed, excluding CT results from Institution No publication shall be initiated by PI until: 18 months after the conclusion of the Study, defined as the locking of the clinical database the publication of a Multicenter Publication (publication of results from all participating sites) written notice from Sponsor that no Multicenter Publication shall ensue PI shall provide a draft of proposed publication for review at least 60 days in advance
Results Point of Contact
| Name/Title | Clinical Support & Regulatory Intelligence, Regulatory Affairs Director |
|---|---|
| Organization | Vifor Pharma Inc. |
| Phone | +1 250 708 4296 |
| Clive.Burge@viforpharma.com |
Responsible Party:
Relypsa, Inc.
ClinicalTrials.gov Identifier:
NCT03071263
Other Study ID Numbers:
- RLY5016-207
- 2016-002657-38
First Posted:
Mar 6, 2017
Last Update Posted:
May 12, 2021
Last Verified:
May 1, 2021