A clinical trial to test if RLY5016 is safe and can lower high blood potassium levels in patients with high blood pressure and kidney disease due to diabetes who are also taking standard medications for their disease.

Conditions: Hyperkalemia in Patients with Hypertension and Diabetic Nephropathy
MedDRA version: 14.0Level: PTClassification code 10020772Term: HypertensionSystem Organ Class: 10047065 - Vascular disorders
MedDRA version: 14.0Level: LLTClassification code 10020647Term: HyperkalemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 14.0Level: PTClassification code 10061835Term: Diabetic nephropathySystem Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2011-000165-12-AT

Lead Sponsor: Relypsa, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

Patients must meet ALL of the following inclusion criteria:
1. Age 30 – 80 years old at screening
2. Type 2 diabetes mellitus (T2DM) diagnosed after age 30 which has been treated with oral medications or
insulin for at least one year prior to screening
3. Chronic kidney disease eGFR 15 – < 60 mL/min/1.73m2 at screening based on central laboratory serum creatinine measurement(except for patients
with hyperkalemia at S1, whose eligibility will be assessed based on
local lab eGFR value)
4.Urine ACR:
a)Cohorts 1 and 2: urine ACR = 30 mg/g at screening (S1) AND average urine ACR = 30 mg/g at the beginning of Run-In Period
(R0) based on up to 3 ACR values obtained starting at S1 and ending at the R0 Visit
b)Cohort 3: not applicable
5.a)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 RLY5016 (Baseline, T0 Visit)
b)Cohort 3: > 5.0 – < 6.0 mEq/L at S1 OR at R0 after same day
confirmation
6. Must be receiving an ACEI and/or ARB for at least 28 days prior to screening
7. Average SBP = 140 – < 180 mmHg OR average diastolic blood DBP= 90 – < 110 mmHg (sitting) at screening
8. 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 RLY5016 administration, during the study, and for one month after study completion
9. Provide their written informed consent prior to participation in the study
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

Patients must NOT meet ANY of the following exclusion criteria:
1. Type 1 diabetes mellitus
2. Central Lab hemoglobin A1c > 12% at S1 (except for Cohort 3 patients who are hyperkalemic at S1)
3. Emergency treatment for T2DM within the last 3 months
4. Diabetic gastroparesis
5. Non-diabetic chronic kidney disease
6. History of bowel obstruction, swallowing disorders, severe
gastrointestinal disorders or major gastrointestinal surgery (e.g.,
cholectomy)
7. Current diagnosis of NYHA Class III or IV heart failure
8. Body mass index (BMI) = 40 kg/m2
9. Any of the following events having occurred within 2 months prior to screening: unstable angina as judged by the Investigator, unresolved acute coronary syndrome, cardiac arrest or clinically significant ventricular arrhythmias, transient ischemic attack or stroke, use of any intravenous cardiac medication
10. Prior kidney transplant, or anticipated need for transplant during
study participation
11. Active cancer, currently on cancer treatment or history of cancer in
the past two years except for nonmelanocytic skin cancer which is
considered cured
12. History of alcoholism or drug/chemical abuse within 1 year
13. Central Lab liver enzymes [alanine aminotransferase (ALT),
aspartate aminotransferase (AST)] > 3 times upper limit of normal
(except for Cohort 3 patients with hyperkalemia at S1, who will have
local lab ALT and AST)
14. 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
15. Current use of polymer-based drugs (e.g., sevelamer, sodium
polystyrene sulfonate, colesevelam, colestipol, cholestyramine),
phosphate binders (e.g., lanthanum carbonate), or other potassium
or their anticipated need during study participation
16. Current use of lithium
17. 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
18. Use of any investigational product within 30 days or 5 half-lives,
whichever is longer, prior to screening
19. Inability to consume the investigational product, or, in the opinion of the Investigator, inability to comply with the protocol
20. 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 patient or affect the validity of the trial results

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to determine the optimal starting dose of RLY5016 in treating hyperkalemia in patients with hypertension and diabetic nephropathy receiving ACEI and/or ARB drugs, with or without spironolactone;Secondary Objective: The secondary objectives of this study are:<br>•To determine the efficacy of RLY5016 in treating hyperkalemia in patients with hypertension and diabetic nephropathy receiving ACEI and/or ARB drugs, with or without spironolactone<br>•To determine the safety of RLY5016 in treating hyperkalemia in patients with hypertension and diabetic nephropathy receiving ACEI and/or ARB drugs, with or without spironolactone<br>•To evaluate the chronic use of RLY5016;Primary end point(s): Mean change in serum potassium from baseline to week 4 or prior to the initiation of RLY5016 dose titration (if occurs before week 4);Timepoint(s) of evaluation of this end point: Week 4 or earlier if RLY5016 dose titration is initiated before Week 4

Secondary Outcome Measures

Name	Time	Method

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