E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Resistant Hypertension and Chronic Kidney Disease |
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E.1.1.1 | Medical condition in easily understood language |
Hard to treat high blood pressure in patients with Kidney disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to week 12 or last available assessment before any new BP medication |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Placebo and Spironolactone |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Croatia |
France |
Georgia |
Germany |
Hungary |
Serbia |
South Africa |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |