Patiromer for Treatment of Hyperkalaemia in Children Under 12 Years of Age

Официальное название

A 2-Part, Open-Label, Phase 2, Multiple Dose Study to Evaluate the Pharmacodynamic Effects, Safety, and Tolerability of Patiromer in Children Under 12 Years of Age With Hyperkalaemia (EMERALD2)

Обзор

A study to evaluate the pharmacodynamic effects, safety, and tolerability of patiromer in children under 12 years of age with hyperkalaemia.

Вмешательства

• Препарат Patiromer
  Patiromer will be given once daily; In Cohort 3, depending on the dose and the study participant's age, the total daily dose might be split

Первичные конечные точки

• Change in potassium levels (mmol/L) [Срок оценки: From baseline to Day 28]

Вторичные конечные точки (12)

• Change in potassium levels (mmol/L) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Occurrence of treatment-emergent adverse events (TEAEs) [Срок оценки: Part 1: Day 1 up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to follow-up visit (Up to 54 weeks)]
• Occurrence of serious adverse events (SAEs) [Срок оценки: Part 1: Day 1 up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to follow-up visit (Up to 54 weeks)]
• Change from baseline in resting heart rate (beats per minute) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Change from baseline in systolic blood pressure (mmHg) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Change from baseline in diastolic blood pressure (mmHg) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Change from baseline in body temperature (Celsius) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Number of patients with ECG abnormalities [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Change from baseline in chemistry laboratory evaluation: Calcium (mg/dL) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Change from baseline in chemistry laboratory evaluation: Phosphate (mg/dL) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Change from baseline in chemistry laboratory evaluation: Magnesium (mg/dL) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]
• Change from baseline in chemistry laboratory evaluation: Potassium (mEq/L) [Срок оценки: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks]

Критерии участия

Критерии включения

• Paediatric participants (<12 years of age) with hyperkalaemia at screening.
• Participant's age should not reach 12 years during the 28 days of the pharmacodynamic/dose-ranging period.
• Participant is able to receive regular external feeding and medication, including via tubes, i.e., percutaneous endoscopic gastrostomy (PEG) or entero-gastric feeding tube.
• At screening/baseline, the results from 2 separate and consecutive potassium assessments using the same measurement method (whole blood, plasma, or serum) need to be above the age-appropriate upper limit of normal (ULN).
• If taking any renin-angiotensin aldosterone system inhibitors (RAASi), beta blockers, fludrocortisone, or diuretic medications, must be on a stable dose for at least 14 days prior to screening.
• Parent(s) or legally authorised representative(s) or another appropriate person delegated by the legally authorised representatives must be available to help the study-site personnel ensure follow-up; accompany the participant to the study site on each assessment day; accurately and reliably dispense investigational product as directed.
• Females of childbearing potential must be non-lactating, must have a negative pregnancy test at screening, and must have used an effective, acceptable form of contraception (e.g., abstinence) for at least 1 month before patiromer administration. Females of childbearing potential must agree to continue using contraception throughout the study and for 1 month after the last dose of patiromer.
• If undergoing peritoneal dialysis, participants must be on a stable treatment plan for a minimum of 4 weeks prior to screening, or at least 8 weeks prior to screening if newly initiated on peritoneal dialysis.

Критерии исключения

• Preterm birth infants with <37 weeks of gestation cannot be included in Cohort 3.
• Participants who due to their general condition, e.g., anaemia or low body weight, are not suitable to have blood volume withdrawn.
• Any of the following renal conditions: maintenance haemodialysis, renal artery stenosis, and acute kidney injury (defined by 2012 Kidney Disease Improving Global Outcomes) or a history of acute renal insufficiency in the past 3 months. Note: Chronic kidney disease (CKD) is not excluded.
• A history of or current diagnosis of a severe gastrointestinal (GI) diagnosis or surgery that could affect GI transit of the drug (delayed gastric emptying), such as a severe swallowing disorder, severe gastroesophageal reflux, 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. Pre-gastric above-mentioned pathologies may be disregarded in case of existence of a PEG or entero-gastric feeding tube, as the PEG or entero-gastric feeding tube will serve for nutrition and investigational product administration.
• Active cancer, currently on cancer treatment, or history of cancer in the past 2 years (except for non-melanoma skin cancer).
• Scheduled for kidney transplant procedure during the first 28 days after Day 1.
• History of sudden infant death in a sibling (only for participants <2 years of age at screening).
• 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 4-week pharmacodynamic/
• Dose-ranging period: digoxin, bronchodilators, theophylline, heparins (including low molecular heparins), tacrolimus, mycophenolate mofetil, cyclosporine, trimethoprim, or cotrimoxazole.
• Use of any investigational product for an unapproved indication within 30 days prior to screening or within 5 half-lives, whichever is longer.
• Known hypersensitivity to patiromer or its components.
• If the child is being breastfed:

• There is suspicion of current alcohol or substance misuse/abuse in breastfeeding mother.
• The breastfeeding mother is taking potassium supplements
• Other protocol defined Inclusion/Exclusion criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 13 центров

• Children's Hospital Colorado — Aurora
• UF Health Pediatric Multispecialty Center Site — Jacksonville
• Miller School of Medicine, University of Miami — Miami
• Arnold Palmer Hospital for Children — Orlando
• Augusta University - Children's Hospital of Georgia — Augusta
• University of Illinois College of Medicine — Peoria
• Boston Children's Hospital — Boston
• Children's Mercy Hospitals and Clinics — Kansas City
• … и ещё 5 центров

Австралия · 3 центра

• Monash Medical Centre Clayton — Clayton
• The Royal Children's Hospital (RCH) — Parkville
• Children's Hospital Westmead Centre for Kidney Research — Westmead

Франция · 3 центра

• CHRU Montpellier - Arnaud de Villeneuve — Montpellier
• Assistance Publique-Hopitaux de Paris Robert-Debre — Paris
• Hôpital des Enfants - Toulouse — Toulouse

Саудовская Аравия · 3 центра

• King Saud University — Riyadh
• King Faisal Specialist Hospital & Research Centre — Riyadh
• King Abdulaziz Medical City — Riyadh

Бельгия · 2 центра

• Universitair Ziekenhuis Gent — Ghent
• UZ Leuven — Leuven

Греция · 2 центра

• Ippokratio Thessaloniki General Hospital — Thessaloniki
• Pan and Aglaia Kyriakou Children's Hospital — Athens

Израиль · 2 центра

• Shaare Zedek Medical Center — Jerusalem
• Schneider Children's Medical Center of Israel — Petach Tikvah

Италия · 2 центра

• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan
• IRCCS Ospedale Pediatrico Bambino Gesù — Rome

Финляндия · 1 центр

• Helsingin Yliopistollinen Keskussairaala Uusi Lastensairaala — Helsinki

Норвегия · 1 центр

• Helse Bergen HF Haukeland Universitetssjukehus — Bergen

Польша · 1 центр

• Uniwersytecki Szpital Kliniczny we Wrocławiu — Wroclaw

Португалия · 1 центр

• Unidade Local de Saude de Santo Antonio, E.P.E. — Porto

Катар · 1 центр

• Sidra Medicine — Doha

Румыния · 1 центр

• Spitalul Clinic de Urgenta pentru Copii Louis Turcanu Timisoara — Timișoara

ОАЭ · 1 центр

• Al Jalila Children's Hospital — Dubai

Идентификаторы

NCT: NCT05766839 · RLY5016-208p · 2023-505252-21-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗