A study of Patiromer alongside Spironolactone to control Blood Pressure in patients with Resistant Hypertension (high blood pressure that does not easily respond to medication) and Chronic Kidney Disease.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-002657-38-HU
• Date of registration: 16/11/2016
• Prospective Registration: Yes
• Primary sponsor: Relypsa, Inc
• Public title: A study of Patiromer alongside Spironolactone to control Blood Pressure in patients with Resistant Hypertension (high blood pressure that does not easily respond to medication) and Chronic Kidney Disease.
• Scientific 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: Evaluation of Safety and Efficacy (AMBER) - Spironolactone with Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease
• Date of first enrolment: 09/01/2017
• Target sample size: 290
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002657-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Placebo and Spironolactone Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Croatia, France, Georgia, Germany, Hungary, Serbia, South Africa, Ukraine, United Kingdom, United States

Contacts

• Name: Maia Abdushelishvili
• Affiliation: Worldwide Clinical Trials Limited

• Name: Maia Abdushelishvili
• Affiliation: Worldwide Clinical Trials Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Eligible subjects must meet all the following criteria:
1. Provide written informed consent prior to participation in the study
2. Age = 18 years
3. Taking at least three antihypertensive medications, one of which is a diuretic, for at least 28 days at a stable dose. ACE inhibitors or ARBs should be included among these three antihypertensive medications, unless previously not tolerated or contraindicated.
4. Uncontrolled hypertension as documented by AOBP SBP 135 to 160 mmHg at each Screening Visit; however, AOBP SBP may be < 135 mmHg at either S2 or S3 Visits
5. eGFR of 25 – = 45 mL/min/1.73 m2 (mean [calculated by the IWRS] of two values measured at S1 and S3 or 7 to 28 days apart during the Screening/Run-in and calculated using CKD Epidemiology Collaboration [CKD-EPI] formula)
6. Qualifying local laboratory K+ measurements of 4.3 – 5.1 mEq/L obtained at Visits S1, S3 and S4 (all measurements must be within range)
7. Females of child-bearing potential must be non-lactating, must have a negative serum pregnancy test at screening, must use a medically acceptable form of birth control from 28 days prior to screening through the study and for 28 days after completion of the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 174
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 116

Exclusion criteria:
Subjects must not meet any of the following criteria:
1. History of untreated secondary causes of hypertension (other than CKD) including but not limited to Cushing’s syndrome, primary hyperaldosteronism, renal vascular stenosis, or coarctation of the aorta
2. Inability to measure BP (e.g., the largest sized arm BP cuff is inadequate given the circumference of the subject’s arm)
3. Noncompliance with antihypertensive medications, in the investigator’s judgment
4. Change in renal function requiring hospitalization or dialysis within 3 months prior to screening
5. Renal transplant or anticipated need for renal transplantation during planned study participation
6. History of malignancy within the previous 12 months except for cured non-melanocytic skin cancer
7. Recent cardiovascular event (within the last 3 months): myocardial infarction, unstable angina, hospitalization for heart failure, revascularization, or stroke (or transient ischemic attack)
8. Clinically significant ventricular arrhythmia
9. Atrial fibrillation with HR > 100 bpm
10. Previous use of patiromer in a clinical study
11. Any current use of spironolactone or other mineralocorticoid antagonists (e.g., eplerenone)
12. Hypersensitivity to patiromer, spironolactone, or any of their components
13. Use of any of the following permitted potassium-altering chronic medications if doses have not been stable for at least 28 days prior to screening or if doses are anticipated to change during study participation: bronchodilators, theophylline, heparin, and canagiflozin
14. Use of the following prohibited medications within 7 days prior to Screening: calcium acetate or calcium carbonate supplements (unless for occasional antacid use, at the discretion of the Investigator), digoxin, direct renin inhibitors (e.g., aliskiren), lanthanum carbonate, lithium, sevelamer, quinidine, sodium polystyrene sulfonate or calcium polystyrene sulfonate, colesevelam, colestipol, cholestyramine, drospirenone, potassium supplements, bicarbonate or baking soda (unless for occasional antacid use, at the discretion of the Investigator), triamterene, amiloride, trimethoprim, tacrolimus, cyclosporine, systemic glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (with the exception of low dose aspirin), sympathomimetics
15. Use of any investigational product within 30 days or 5 half-lives, whichever is longer, prior to screening
16. History of bowel obstruction, swallowing disorders, clinically significant gastroparesis, severe gastrointestinal disorders or major gastrointestinal surgery (e.g., large bowel resection)
17. Inability to take the study medications or comply with the protocol, in the opinion of the Investigator
18. History of alcohol or drug abuse within 1 year of screening
19. Any medical condition, uncontrolled systemic disease, or serious intercurrent illness that would significantly decrease study compliance or jeopardize the safety of the subject or affect the validity of the trial results, in the opinion of the Investigator


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Resistant Hypertension and Chronic Kidney Disease
MedDRA version: 20.0 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders
MedDRA version: 20.0 Level: PT Classification code 10020772 Term: Hypertension System Organ Class: 10047065 - Vascular disorders

Intervention(s)

Product Name: Patiromer for Oral Suspension
Product Code: RLY5016
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: Patiromer
CAS Number: 1415477-49-4
Current Sponsor code: RLY5016
Other descriptive name: PATIROMER
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 4.2-
Pharmaceutical form of the placebo: Powder for oral suspension
Route of administration of the placebo: Oral use

Trade Name: Aldactone
Product Name: Aldactone 25 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: Aldactone
Other descriptive name: SPIRONOLACTONE BP
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline to week 12

Main Objective: To determine if patiromer treatment of CKD subjects receiving spironolactone for the treatment of resistant hypertension will result in:
• More persistent use of spironolactone through prevention of hyperkalemia
• Improved blood pressure control through more persistent use of spironolactone

Primary end point(s): The proportion of subjects remaining on spironolactone at Week 12 will be compared between treatment groups (spironolactone/patiromer vs. spironolactone/placebo) using the Cochran-Mantel-Haenszel test, stratified by baseline serum potassium category (K+ 4.3 – < 4.7 mEq/L or 4.7 – 5.1 mEq/L).

Secondary Objective: Not applicable

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline to week 12 or last available assessment before any new BP medication

Secondary end point(s): AOBP SBP change from baseline to Week 12 or last available assessment prior to addition of any new BP medications or changes to any baseline BP medications will be analyzed using analysis of covariance (ANCOVA) methods.

Secondary ID(s)

RLY5016-207

75,615

Source(s) of Monetary Support

Relypsa, Inc.

Ethics review

Status: Approved
Approval date:
Contact: