E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Kidney Disease and Hyperkalemia |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Kidney Disease and High Levels of Potassium in the blood |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020647 |
E.1.2 | Term | Hyperkalemia |
E.1.2 | System Organ Class | 100000004861 |
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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 assess change from baseline in serum potassium levels to Day 14 following administration of different doses of patiromer administered once daily in children 2 – < 18 years of age with chronic kidney disease (CKD) and hyperkalemia. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of patiromer in children 2 – < 18 years of age with CKD and hyperkalemia. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Written assent (when applicable) and written informed consent by a legally authorized representative provided prior to participation in the study 2.Age 2 – < 18 years old (subject’s age should not exceed that of the age cohort into which s/he is enrolled for at least the entire 14 days of the PD / Dose Finding Phase) 3.Pediatric subjects with CKD and eGFR < 90 mL/min/1.73m2 calculated using the Schwartz formula as described in Section 7.2, including renal transplant and peritoneal dialysis subjects, based on local creatinine measurement at Screening 4.Two blood or serum potassium measurements of 5.1 to < 6.5 mEq/L performed on separate days 5.In the opinion of the Investigator, the subject is expected to require treatment for hyperkalemia for at least 6 months 6.If taking any renin-angiotensin aldosterone system inhibitors (RAASi), beta blockers, fludrocortisone or diuretic medications, must be on a stable dose for at least 28 days prior to Screening 7.Females of child-bearing potential must be non-lactating, must have a negative pregnancy test at Screening, and must have used an effective form of contraception (e.g. abstinence, hormonal, chemical, physical barrier, etc.) for at least 1 month before patiromer administration. Subjects of child-bearing potential must agree to continue using contraception throughout the study and for 1 month after the last dose of patiromer
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E.4 | Principal exclusion criteria |
1.Subjects with pseudohyperkalemia due to hemolysis or to abnormally high numbers of platelets (> 500,000/mm³), leukocytes (> 70,000/mm³), or erythrocytes (hematocrit > 55%) at Screening based on results obtained locally 2.Any subject with evidence of potential potassium-related ECG changes (i.e., changes consistent with hyper- or hypokalemia) at Screening 3.Any of the following renal conditions: maintenance hemodialysis or peritoneal dialysis, renal artery stenosis, and acute kidney injury (defined by 2012 Kidney Disease Improving Global Outcomes [KDIGO], 2012) or a history of acute renal insufficiency in the past 3 months 4.A history of or current diagnosis of a severe gastrointestinal diagnosis or surgery that could affect gastrointestinal transit of the drug (e.g. a severe swallowing disorder, uncorrected pyloric stenosis, intussusception, any other intestinal obstruction [e.g., Hirschsprung disease, chronic intestinal pseudo-obstruction, clinically significant postsurgical abdominal adhesions] or any gut-shortening surgical procedure prior to Screening) 5.A history of or current diagnosis of a condition that in the opinion of the investigator increases the risk of aspiration of patiromer if it will be given orally 6.Liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST) > three times upper limit of normal at Screening, based on the local laboratory ALT and AST 7.Active cancer, currently on cancer treatment or history of cancer in the past 2 years (except for non-melanoma skin cancer) 8.Heart or liver transplant recipient, or anticipated need for transplant during the study Treatment Period, including a scheduled kidney transplant recipient (note: patients currently on a kidney transplant wait list are not excluded unless there is an identified donor) 9.Chronic alcohol abuse or substance use disorder within 1 year of Screening 10.Subjects currently being treated with or having taken any one of the following medications (includes resins) in the 7 days prior to Screening: sodium or calcium polystyrene sulfonate, sodium zirconium cyclosilicate, and drospirenone 11.Use of the following medications if doses have not been stable for at least 14 days prior to Screening or if doses are anticipated to change during the 14-day PD / Dose Finding Phase: -digoxin; -bronchodilators; -theophylline; -heparins (including low molecular heparins); -canagliflozin; -tacrolimus; -mycophenolate mofetil; -cyclosporine - trimethoprim or cotrimoxazole 12.Use of any investigational product for an unapproved indication within 30 days prior to Screening or within 5 half-lives, whichever is longer 13.Known hypersensitivity to patiromer or its components 14.In the opinion of the Investigator, inability to comply with the protocol 15.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 subject or potentially affect the quality of the data such as: hyperkalemia at Screening that requires emergency intervention; cardiovascular event or intervention within 3 months prior to Screening; a hemodynamically unstable arrhythmia; hospitalization for heart failure within the past 3 months; poorly controlled blood pressure (BP); poorly controlled diabetes mellitus or frequent need for adjustment in insulin prescription or recent hospitalization for treatment of hyper or hypoglycemia
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in serum potassium levels from baseline to Day 14. |
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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) |
Proportion of subjects with serum potassium levels in the range of 3.8 – 5.0 mEq/L at Day 14 (Initial Pharmacodynamic [PD] / Dose Finding Phase)
Proportion of subjects with serum potassium levels in the range of 3.8 – 5.0 mEq/L by visit through Month 6 (Long-Term Treatment Phase)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Canada |
Georgia |
South Africa |
Ukraine |
United States |
Bulgaria |
Germany |
Poland |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |