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

• Sponsor: Relypsa, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01371747
• Collaborator: (none)
• Enrollment: 324
• Locations: 43
• Arms: 6
• Duration (Months): 24
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study determined the optimal starting dose of patiromer in treating hyperkalemia in participants with hypertension and diabetic nephropathy who were already receiving ACEI and/or ARB drugs, with or without spironolactone. This study also evaluated the efficacy and safety of patiromer and the long term use of patiromer.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease; Hypertension; Hyperkalemia	Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: losartan; Drug: spironolactone	Phase 2

Detailed Description

RLY5016-205 was an open-label, randomized, dose ranging study to determine the optimal starting dose, efficacy and safety of patiromer in treating hyperkalemia in hypertensive patients with nephropathy due to type 2 diabetes mellitus (T2DM) who were already receiving Angiotensin-converting Enzyme Inhibitor (ACEI) and/or Angiotensin II Receptor Blocker (ARB) drugs, with or without spironolactone.

The study consisted of the following periods:

• Screening: Up to 10 days (1 visit)

• Run-in for those who were not hyperkalemic at screening (Cohorts 1 and 2): up to 4 weeks (1 to 4 visits)

• Patiromer Treatment Initiation: first 8 weeks of patiromer treatment (a minimum of 10 visits)

• Patiromer Long-Term Maintenance: additional 44 weeks of patiromer treatment up to a total of one year (minimum of 11 additional visits)

• Follow-up (after patiromer discontinuation): 1 week (2 visits) OR 4 weeks (5 visits) depending on the final serum potassium level

Study Design

• Study Type: Interventional
• Actual Enrollment: 324 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Open-Label, Dose Ranging Study to Evaluate the Efficacy and Safety of Patiromer in the Treatment of Hyperkalemia in Patients With Hypertension and Diabetic Nephropathy Receiving Angiotensin-converting Enzyme Inhibitor (ACEI) and/or Angiotensin II Receptor Blocker (ARB) Drugs, With or Without Spironolactone
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stratum 1: 8.4 g/d patiromer Participants with baseline serum potassium > 5.0 to 5.5 mEq/L (milliequivalent)	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 8.4 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: RLY5016 for Oral Suspension Veltassa ; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 1: 16.8 g/d patiromer Participants with baseline serum potassium > 5.0 to 5.5 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: RLY5016 for Oral Suspension Veltassa ; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 1: 25.2 g/d patiromer Participants with baseline serum potassium > 5.0 to 5.5 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1); Other Names: RLY5016 for Oral Suspension Veltassa ; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 2: 16.8 g/d patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 16.8 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: RLY5016 for Oral Suspension Veltassa ; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 2: 25.2 g/d patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 25.2 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: RLY5016 for Oral Suspension Veltassa ; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Experimental: Stratum 2: 33.6 g/d patiromer Participants with baseline serum potassium > 5.5 to < 6.0 mEq/L	Drug: patiromer; Cohorts 1, 2 and 3 - Patiromer starting dose: 33.6 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response. (Stratum 2); Other Names: RLY5016 for Oral Suspension Veltassa ; Drug: losartan; losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1); Drug: spironolactone; Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)

Outcome Measures

Primary Outcome Measures

1. Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group [Baseline to Week 4 or First Titration which could occur at any scheduled study visit after patiromer initiation.]

   Least square mean changes from Baseline to Week 4/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.

Secondary Outcome Measures

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

   Least squares mean changes from Baseline to Week 8/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.

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

   Least squares mean changes from Baseline to Day 3 were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.

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

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

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

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

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

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 30 - 80 years old at screening (S1)

2. Type 2 diabetes mellitus (T2DM) diagnosed after age 30 which has been treated with oral medications or insulin for at least 1 year prior to S1

3. Chronic kidney disease (CKD): estimated glomerular filtration rate (eGFR) 15 - < 60 mL/min/1.73m2 at screening based on central lab serum creatinine measurement (except for participants with hyperkalemia at S1), whose eligibility will be assessed based on local lab eGFR value)

4. Urine albumin/creatinine ratio (ACR):

5. Cohorts 1 and 2: urine ACR ≥ 30 mg/g at S1 AND average urine ACR ≥ 30 mg/g at the beginning of Run-In Period (R0) based on up to three ACR values obtained starting at S1 and ending at the R0 Visit

6. Cohort 3: not applicable

7. Local laboratory serum potassium (K+) values of:

8. Cohorts 1 and 2: 4.3 - 5.0 mEq/L at S1; AND 4.5 - 5.0 mEq/L at R0; AND > 5.0 - < 6.0 mEq/L at randomization to patiromer (Baseline, T0 Visit)

9. Cohort 3: > 5.0 - < 6.0 mEq/L at S1 OR at R0 after same day confirmation

10. Must be receiving an ACEI and/or ARB for at least 28 days prior to screening

11. Average systolic blood pressure (SBP) ≥ 130 - < 180 mmHg AND average DBP ≥ 80 - < 110 mmHg (sitting) at both screening and R0 (as applicable)

12. Females of child-bearing potential must be non-lactating, must have a negative serum pregnancy test at screening, and must have used a highly effective form of contraception for at least 3 months before patiromer administration, during the study, and for one month after study completion

13. Provide their written informed consent prior to participation in the study

Exclusion Criteria:

1. Type 1 diabetes mellitus

2. Central lab hemoglobin A1c > 12% at Screening 1 (S1) (except for Cohort 3 participants who are hyperkalemic at S1)

3. Emergency treatment for T2DM within the last 3 months

4. A confirmed SBP > 180 mmHg or diastolic blood pressure (DBP) > 110 mmHg at any time during SI or Run-In Period or at Baseline T0 Visit

5. Central lab serum magnesium < 1.4 mg/dL (< 0.58 mmol/L) at screening (Cohort 3 participants will be evaluated based on local lab serum magnesium measurement)

6. Central lab urine ACR ≥ 10000 mg/g at screening (except for Cohort 3 participants who are hyperkalemic at S1)

7. Confirmed diagnosis or history of renal artery stenosis (unilateral or bilateral)

8. Diabetic gastroparesis

9. Non-diabetic chronic kidney disease

10. History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery (e.g., large bowel resection)

11. Current diagnosis of NYHA (New York Heart Association) Class III or IV heart failure

12. Body mass index (BMI) ≥ 40 kg/m2

13. Any of the following events having occurred within 2 months prior to screening: unstable angina as judged by the Principal Investigator (PI), unresolved acute coronary syndrome, cardiac arrest or clinically significant ventricular arrhythmias, transient ischemic attack or stroke, use of any intravenous cardiac medication

14. Prior kidney transplant, or anticipated need for transplant during study participation

15. Active cancer, currently on cancer treatment or history of cancer in the past 2 years except for non-melanocytic skin cancer which is considered cured

16. History of alcoholism or drug/chemical abuse within 1 year

17. Central lab liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] > 3 times upper limit of normal at S1 (except for Cohort 3 patients with hyperkalemia at S1, who will have local lab ALT and AST)

18. Loop and thiazide diuretics or other antihypertensive medications (calcium channel blocker, beta-blocker, alpha-blocker, or centrally acting agent) that have not been stable for at least 28 days prior to screening or not anticipated to remain stable during study participation

19. Current use of polymer-based drugs (e.g., sevelamer, sodium polystyrene sulfonate, colesevelam, colestipol, cholestyramine), phosphate binders (e.g., lanthanum carbonate), or other potassium binders, or their anticipated need during study participation

20. Current use of lithium

21. Use of potassium sparing medications, including aldosterone antagonists (e.g., spironolactone), drospirenone, potassium supplements, bicarbonate or baking soda in the last 7 days prior to screening

22. Use of any investigational product within 30 days or 5 half-lives, whichever is longer, prior to screening

23. Inability to consume the investigational product, or, in the opinion of the Investigator, inability to comply with the protocol

24. In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, or serious intercurrent illness that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site 201	Karlovac		Croatia	47000
2	Investigator Site 207	Osijek		Croatia	31000
3	Investigator Site 203	Rijeka		Croatia	51000
4	Investigator Site 202	Zagreb		Croatia	10000
5	Investigator Site 204	Zagreb		Croatia	10000
6	Investigator Site 208	Zagreb		Croatia	10000
7	Investigator Site 305	Tbilisi		Georgia	0102
8	Investigator Site 309	Tbilisi		Georgia	0144
9	Investigator site 301	Tbilisi		Georgia	0159
10	Investigator Site 302	Tbilisi		Georgia	0159
11	Investigator Site 303	Tbilisi		Georgia	0159
12	Investigator Site 304	Tbilisi		Georgia	0159
13	Investigator Site 306	Tbilisi		Georgia	0159
14	Investigator Site 307	Tbilisi		Georgia	0159
15	Investigator Site 310	Tbilisi		Georgia	0159
16	Investigator Site 311	Tbilisi		Georgia	0159
17	Investigator Site 308	Tbilisi		Georgia	0186
18	Investigator Site 508	Budapest		Hungary	1097
19	Investigator Site 502	Budapest		Hungary	1106
20	Investigator Site 514	Budapest		Hungary	H-1041
21	Investigator Site 513	Budapest		Hungary	H-1097
22	Investigator Site 517	Budapest		Hungary	H-1115
23	Investigator Site 522	Gyor		Hungary	H-9024
24	Investigator Site 523	Hatvan		Hungary	3000
25	Investigator Site 515	Jaszbereny		Hungary	H-5100
26	Investigator Site 506	Kistarcsa		Hungary	H-2143
27	Investigator Site 503	Kisvarda		Hungary	4600
28	Investigator Site 510	Mosonmagyarovar		Hungary	H-9200
29	Investigator Site 504	Szekesfehervar		Hungary	H-8000
30	Investigator Site 505	Szikszo		Hungary	3800
31	Investigator Site 507	Veszprem		Hungary	H-8200
32	Investigator Site 601	Belgrade		Serbia	11000
33	Investigator Site 602	Belgrade		Serbia	11000
34	Investigator Site 604	Belgrade		Serbia	11000
35	Investigator Site 605	Belgrade		Serbia	11000
36	Investigator Site 603	Novi Sad		Serbia	21000
37	Investigator Site 607	Zrenjanin		Serbia	23000
38	Investigator Site 703	Celje		Slovenia	3000
39	Investigator Site 706	Golnik		Slovenia	4204
40	Investigator Site 708	Jesenice		Slovenia	4270
41	Investigator Site 701	Maribor		Slovenia	2000
42	Investigator Site 704	Slovenj Gradec		Slovenia	2380
43	Investigator Site 707	Šempeter pri Gorici		Slovenia	5290

Sponsors and Collaborators

• Relypsa, Inc.

Investigators

• Study Director: Director Clinical Operations, Relypsa, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Relypsa company website

Publications

• Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, Garza D, Stasiv Y, Zawadzki R, Berman L, Bushinsky DA; AMETHYST-DN Investigators. Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial. JAMA. 2015 Jul 14;314(2):151-61. doi: 10.1001/jama.2015.7446. Erratum in: JAMA. 2015 Aug 18;314(7):731. Dosage error in article text.

• Responsible Party: Relypsa, Inc.
• ClinicalTrials.gov Identifier: NCT01371747
• Other Study ID Numbers: RLY5016-205; 2011-000165-12
• First Posted: Jun 13, 2011
• Last Update Posted: Jun 3, 2021
• Last Verified: May 1, 2021

• Keywords provided by Relypsa, Inc.: Hyperkalemia; Chronic Kidney Disease; Treatment of Hyperkalemia; Hypertension; Diabetic Nephropathy
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Hypertension; Hyperkalemia; Losartan; Spironolactone

Study Results

Participant Flow

Recruitment Details	324 participants were enrolled in the study; 306 participants were randomized to receive study drug.
Pre-assignment Detail	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.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Period Title: Overall Study
STARTED	74	74	74	26	28	30
COMPLETED	56	51	50	17	21	16
NOT COMPLETED	18	23	24	9	7	14

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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	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 of all reporting groups
Overall Participants	74	73	73	26	28	30	304
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	28 37.8%	29 39.7%	28 38.4%	12 46.2%	12 42.9%	13 43.3%	122 40.1%
>=65 years	46 62.2%	44 60.3%	45 61.6%	14 53.8%	16 57.1%	17 56.7%	182 59.9%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67	70	68	66.5	68.5	65	67.5
Sex: Female, Male (Count of Participants)
Female	29 39.2%	26 35.6%	26 35.6%	8 30.8%	13 46.4%	10 33.3%	112 36.8%
Male	45 60.8%	47 64.4%	47 64.4%	18 69.2%	15 53.6%	20 66.7%	192 63.2%

Outcome Measures

1. Primary Outcome

Title	Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group
Description	Least square mean changes from Baseline to Week 4/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.
Time Frame	Baseline to Week 4 or First Titration which could occur at any scheduled study visit after patiromer initiation.

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	73	72	72	26	27	30
Least Squares Mean (Standard Error) [mEq/L]	-0.35 (0.066)	-0.51 (0.067)	-0.55 (0.067)	-0.87 (0.134)	-0.97 (0.132)	-0.92 (0.125)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 8.4 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 33.6 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group
Description	Least squares mean changes from Baseline to Week 8/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.
Time Frame	Baseline to Week 8 or First Titration which could occur at any scheduled study visit after patiromer initiation.

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	73	72	72	26	27	30
Least Squares Mean (Standard Error) [mEq/L]	-0.35 (0.070)	-0.47 (0.070)	-0.54 (0.070)	-0.88 (0.142)	-0.95 (0.139)	-0.91 (0.132)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 8.4 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 33.6 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group
Description	Least squares mean changes from Baseline to Day 3 were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.
Time Frame	Baseline to Day 3

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	68	63	69	25	26	30
Least Squares Mean (Standard Error) [mEq/L]	-0.26 (0.048)	-0.28 (0.050)	-0.31 (0.047)	-0.65 (0.086)	-0.59 (0.084)	-0.53 (0.079)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 8.4 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 33.6 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value <0.001
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	50	49	44	15	19	15
Mean (Standard Deviation) [mEq/L]	-0.54 (0.465)	-0.44 (0.440)	-0.50 (0.417)	-1.00 (0.466)	-0.96 (0.414)	-1.17 (0.569)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 8.4 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 33.6 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.17
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

5. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	52	52	50	20	17	20
Mean (Standard Deviation) [mEq/L]	0.36 (0.567)	0.22 (0.424)	0.30 (0.508)	0.41 (0.660)	0.39 (0.331)	0.58 (0.557)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 8.4 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.36
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.22
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 16.8 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 25.2 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.39
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 33.6 g/d Patiromer
	Comments	Each starting dose group was compared to its baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated values were based on summary statistics.

6. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	63	65	64	24	24	22
Number (95% Confidence Interval) [percentage of participants]	100 135.1%	100 137%	98.4 134.8%	91.7 352.7%	95.8 342.1%	95.5 318.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 8.4 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	100
	Confidence Interval	(2-Sided) 95%; 94.3 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 16.8 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	100
	Confidence Interval	(2-Sided) 95%; 94.5 to 100
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 25.2 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	98.4
	Confidence Interval	(2-Sided) 95%; 91.6 to 100
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 16.8 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	91.7
	Confidence Interval	(2-Sided) 95%; 73 to 99
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 25.2 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	95.8
	Confidence Interval	(2-Sided) 95%; 78.9 to 99.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 33.6 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	95.5
	Confidence Interval	(2-Sided) 95%; 77.2 to 99.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

7. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	63	65	64	24	24	22
Number (95% Confidence Interval) [percentage of participants]	95.2 128.6%	90.8 124.4%	81.3 111.4%	79.2 304.6%	91.7 327.5%	77.3 257.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 8.4 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	95.2
	Confidence Interval	(2-Sided) 95%; 86.7 to 99.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 16.8 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	90.8
	Confidence Interval	(2-Sided) 95%; 81.0 to 96.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 25.2 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	81.3
	Confidence Interval	(2-Sided) 95%; 69.5 to 89.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 16.8 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	79.2
	Confidence Interval	(2-Sided) 95%; 57.8 to 92.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 25.2 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	91.7
	Confidence Interval	(2-Sided) 95%; 73 to 99
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 33.6 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	77.3
	Confidence Interval	(2-Sided) 95%; 54.6 to 92.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

8. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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	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.	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.	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.	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.	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.
Measure Participants	72	72	73	26	28	30
Median (95% Confidence Interval) [Days]	4	4	4	8	7.5	8

9. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	58	63	59	22	24	20
Number (95% Confidence Interval) [percentage of participants]	86.3 116.6%	81.6 111.8%	88.9 121.8%	86.7 333.5%	89.5 319.6%	93.3 311%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 8.4 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	86.3
	Confidence Interval	(2-Sided) 95%; 73.7 to 94.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 16.8 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	81.6
	Confidence Interval	(2-Sided) 95%; 68.0 to 91.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Stratum 1: 25.2 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	88.9
	Confidence Interval	(2-Sided) 95%; 75.9 to 96.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 16.8 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	86.7
	Confidence Interval	(2-Sided) 95%; 59.5 to 98.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 25.2 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	89.5
	Confidence Interval	(2-Sided) 95%; 66.9 to 98.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Stratum 2: 33.6 g/d Patiromer
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	93.3
	Confidence Interval	(2-Sided) 95%; 68.1 to 99.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% exact binomial CI

Adverse Events

Time Frame	Up to 28 days after Week 52 or last patiromer dose, whichever was earlier
Adverse Event Reporting Description	Randomized participants who received at least one dose of trial medication
Arm/Group Title	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
Arm/Group Description	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.		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.		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.		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.		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.		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.
All Cause Mortality
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/74 (12.2%)		10/73 (13.7%)		10/73 (13.7%)		6/26 (23.1%)		5/28 (17.9%)		4/30 (13.3%)
Cardiac disorders
Acute left ventricular failure	1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Acute myocardial infarction	0/74 (0%)		0/73 (0%)		0/73 (0%)		1/26 (3.8%)		0/28 (0%)		1/30 (3.3%)
Angina pectoris	0/74 (0%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		1/28 (3.6%)		0/30 (0%)
Atrial fibrillation	0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Atrioventricular block complete	0/74 (0%)		0/73 (0%)		0/73 (0%)		1/26 (3.8%)		0/28 (0%)		0/30 (0%)
Cardiac failure	0/74 (0%)		0/73 (0%)		0/73 (0%)		1/26 (3.8%)		1/28 (3.6%)		1/30 (3.3%)
Cardiac failure chronic	0/74 (0%)		1/73 (1.4%)		0/73 (0%)		1/26 (3.8%)		0/28 (0%)		0/30 (0%)
Myocardial infarction	0/74 (0%)		1/73 (1.4%)		1/73 (1.4%)		0/26 (0%)		1/28 (3.6%)		0/30 (0%)
Eye disorders
Diabetic retinopathy	0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Gastrointestinal disorders
Gastric ulcer	0/74 (0%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		1/30 (3.3%)
Gastric ulcer haemorrhage	0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Mesenteric artery thrombosis	0/74 (0%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		1/28 (3.6%)		0/30 (0%)
General disorders
Brain death	0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Sudden cardiac death	0/74 (0%)		0/73 (0%)		3/73 (4.1%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Sudden death	0/74 (0%)		0/73 (0%)		1/73 (1.4%)		1/26 (3.8%)		2/28 (7.1%)		1/30 (3.3%)
Hepatobiliary disorders
Cholecystitis	0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Infections and infestations
Appendicitis	1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Arteriosclerotic gangrene	1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Gastrointestinal infection	0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Pneumonia	0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Urinary tract infection	0/74 (0%)		0/73 (0%)		0/73 (0%)		1/26 (3.8%)		0/28 (0%)		0/30 (0%)
Investigations
Intraocular pressure increased	0/74 (0%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		1/30 (3.3%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Gout	1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Hypoglycaemia	0/74 (0%)		1/73 (1.4%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Hypovolaemia	1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Nervous system disorders
Cerebrovascular accident	1/74 (1.4%)		1/73 (1.4%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Ischaemic stroke	1/74 (1.4%)		0/73 (0%)		1/73 (1.4%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Transient ischaemic attack	1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Renal and urinary disorders
Nephropathy toxic	0/74 (0%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		1/30 (3.3%)
Renal failure chronic	0/74 (0%)		2/73 (2.7%)		1/73 (1.4%)		1/26 (3.8%)		1/28 (3.6%)		1/30 (3.3%)
Tubulointerstitial nephritis	0/74 (0%)		0/73 (0%)		0/73 (0%)		1/26 (3.8%)		0/28 (0%)		0/30 (0%)
Vascular disorders
Diabetic vascular disorder	2/74 (2.7%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Femoral artery occlusion	1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Hypertensive crisis	0/74 (0%)		0/73 (0%)		1/73 (1.4%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Hypotension	1/74 (1.4%)		0/73 (0%)		0/73 (0%)		0/26 (0%)		0/28 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/74 (37.8%)		29/73 (39.7%)		29/73 (39.7%)		14/26 (53.8%)		14/28 (50%)		22/30 (73.3%)
Blood and lymphatic system disorders
Anaemia	2/74 (2.7%)		2/73 (2.7%)		4/73 (5.5%)		0/26 (0%)		1/28 (3.6%)		2/30 (6.7%)
Cardiac disorders
Angina pectoris	0/74 (0%)		1/73 (1.4%)		2/73 (2.7%)		1/26 (3.8%)		2/28 (7.1%)		0/30 (0%)
Cardiac failure chronic	0/74 (0%)		0/73 (0%)		1/73 (1.4%)		2/26 (7.7%)		0/28 (0%)		0/30 (0%)
Ventricular extrasystoles	2/74 (2.7%)		4/73 (5.5%)		2/73 (2.7%)		0/26 (0%)		1/28 (3.6%)		2/30 (6.7%)
Gastrointestinal disorders
Constipation	4/74 (5.4%)		3/73 (4.1%)		4/73 (5.5%)		2/26 (7.7%)		1/28 (3.6%)		5/30 (16.7%)
Diarrhoea	6/74 (8.1%)		5/73 (6.8%)		1/73 (1.4%)		3/26 (11.5%)		1/28 (3.6%)		1/30 (3.3%)
Infections and infestations
Influenza	3/74 (4.1%)		0/73 (0%)		4/73 (5.5%)		1/26 (3.8%)		1/28 (3.6%)		0/30 (0%)
Nasopharyngitis	0/74 (0%)		1/73 (1.4%)		2/73 (2.7%)		1/26 (3.8%)		1/28 (3.6%)		2/30 (6.7%)
Urinary tract infection	3/74 (4.1%)		3/73 (4.1%)		2/73 (2.7%)		0/26 (0%)		2/28 (7.1%)		0/30 (0%)
Metabolism and nutrition disorders
Hypercholesterolaemia	1/74 (1.4%)		2/73 (2.7%)		1/73 (1.4%)		0/26 (0%)		2/28 (7.1%)		0/30 (0%)
Hypoglycaemia	1/74 (1.4%)		1/73 (1.4%)		1/73 (1.4%)		2/26 (7.7%)		1/28 (3.6%)		3/30 (10%)
Hypokalaemia	2/74 (2.7%)		1/73 (1.4%)		0/73 (0%)		1/26 (3.8%)		0/28 (0%)		3/30 (10%)
Hypomagnesaemia	4/74 (5.4%)		5/73 (6.8%)		6/73 (8.2%)		2/26 (7.7%)		4/28 (14.3%)		5/30 (16.7%)
Nervous system disorders
Headache	3/74 (4.1%)		2/73 (2.7%)		1/73 (1.4%)		0/26 (0%)		0/28 (0%)		2/30 (6.7%)
Renal and urinary disorders
Renal failure chronic	5/74 (6.8%)		4/73 (5.5%)		2/73 (2.7%)		2/26 (7.7%)		3/28 (10.7%)		6/30 (20%)
Vascular disorders
Hypertension	5/74 (6.8%)		7/73 (9.6%)		2/73 (2.7%)		4/26 (15.4%)		2/28 (7.1%)		4/30 (13.3%)
Hypotension	0/74 (0%)		1/73 (1.4%)		1/73 (1.4%)		0/26 (0%)		0/28 (0%)		2/30 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.