NCT05766839招募中2 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 38
- 主要终点
- Change in potassium levels (mmol/L)
研究概览
简要总结
A study to evaluate the pharmacodynamic effects, safety, and tolerability of patiromer in children under 12 years of age with hyperkalaemia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •In continuation to above criterion: At least 1 sample needs to be taken at screening/baseline and 1 sample should not be older than 30 days, i.e., a historical sample. The average of the 2 potassium values needs to be above the age-appropriate ULN of the measurement method plus 0.5 mEq/l (equivalent to 0.5 mmol/l). If the 2 samples are taken on the day of screening/baseline, the 2 individual potassium values must not differ from each other by more than 0.5 mEq/l.
- •In the opinion of the Investigator, the participant is expected to require treatment for hyperkalaemia for at least 28 days upon enrolment in the study.
- •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 acceptable representative(s) has provided the appropriate written informed consent, in accordance with local regulations. The assent of the child should also be obtained when appropriate or if requested by the Institutional Review Board (IRB)/Ethics Committee (EC)/Independent Ethics Committee (IEC). The written informed consent must be provided before any study specific procedures are performed including screening procedures.
- •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 according to the Schedule of Events (Table 1, Table 2) (e.g., able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); accurately and reliably dispense investigational product as directed.
- •Not applicable to Norway sites: 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.
- •For participants who have undergone organ transplantation, the general clinical condition must be stable for at least 4 weeks prior to Screening and is not expected to change during the first 4 weeks of the study.
- •For participants who have undergone organ transplantation, must have persistent hyperkalaemia requiring potassium-lowering therapy despite correction of reversible causes (e.g., high calcineurin inhibitor levels).
排除标准
- •Preterm birth infants with <37 weeks of gestation cannot be included in Cohort
- •Participants who due to their general condition, e.g., anaemia or low body weight, are not suitable to have blood volume withdrawn as specified in the Schedule of Events.
- •Participants with pseudo-hyperkalaemia due to haemolysis or to abnormally high numbers of platelets (above ULN), leukocytes (above ULN), or erythrocytes (above ULN) at screening based on results obtained from the local laboratory.
- •Any participant with evidence of potential potassium-related 12-lead electrocardiogram (ECG) changes (i.e., changes consistent with hyper- or hypokalaemia) at screening.
- •Any participant with serum magnesium <1.4 mg/dl (0.58 mmol/l) at screening/baseline.
- •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.
- •In continuation to above criterion: 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.
- •Liver enzymes (alanine aminotransferase or aspartate aminotransferase) more than 3 times the ULN at screening, based on the local laboratory, as well as the participant's respective age.
- •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
- •History of sudden infant death in a sibling (only for participants <2 years of age at screening).
- •Has severe hypoxaemia, respiratory acidosis, asphyxia, or hypotension 3 months before screening based on assessment of the Investigator.
- •Participants treated with sodium polystyrene sulphonate, calcium polystyrene sulphonate, sodium zirconium cyclosilicate, or patiromer within the last 48 hours prior to fulfilling the baseline baseline potassium assessments requested in 4th Inclusion Criterion.
- •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.
- •In the opinion of the Investigator, parent(s) or legal representative(s) inability to comply with the protocol.
- •In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, or serious intercurrent illness that would significantly decrease study compliance or jeopardise the safety of the participant or potentially affect the quality of the data such as:
- •In continuation to above criterion: hyperkalaemia at screening that requires emergency intervention; cardiovascular event or intervention within 3 months prior to screening; a haemodynamically unstable arrhythmia; hospitalisation for heart failure within the past 3 months; poorly controlled blood pressure; poorly controlled diabetes mellitus or frequent need for adjustment in insulin prescription or recent hospitalisation for treatment of hyper or hypoglycaemia.
- •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
研究组 & 干预措施
Patiromer
Experimental
4-week pharmacodynamic /dose-ranging period
Cohort 1: 6 to less than (<)12 years of age Cohort 2: 2 to <6 years of age Cohort 3: 0 to <2 years of age; In Cohort 3, a minimum of 3 study participants will be assessed in the subgroup of 0 to <6 months and another 3 study participants in the subgroup 6 to <24 months of age.
干预措施: Patiromer (Drug)
结局指标
主要结局
Change in potassium levels (mmol/L)
时间窗: From baseline to Day 28
May be measured as serum, plasma, whole blood, potassium
次要结局
- Change in potassium levels (mmol/L)(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)(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(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)(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)(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)(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)(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)(From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks)
- Occurrence of serious adverse events (SAEs)(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 diastolic blood pressure (mmHg)(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: Blood urea nitrogen (mEq/L)(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)(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: Serum bicarbonate (mEq/L)(From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks)
- Occurrence of blood potassium below the lower limit of normal (LLN) (mmol/L)(Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks))
- Occurrence of blood potassium above the upper limit of normal (ULN) (mmol/L)(Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks))
- Change from baseline in chemistry laboratory evaluation: Potassium (mEq/L)(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: Sodium (mEq/L)(From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks)
- Change from baseline in haematology laboratory evaluation: Red blood cells count (10^12/L)(From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52))
- Change from baseline in haematology laboratory evaluation: Haematocrit (%)(From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52))
- Change from baseline in chemistry laboratory evaluation: Creatinine (mg/dL)(From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks)
- Change from baseline in haematology laboratory evaluation: White blood cells (10^9/L)(From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52))
- Change from baseline in haematology laboratory evaluation: Haemoglobin (10^12/L)(From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52))
- Change from baseline in haematology laboratory evaluation: Platelet count (10^9/L)(From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52))
- Occurrence of blood magnesium at levels specified in protocol (mmol/L)(Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks))
- Change from baseline in haematology laboratory evaluation: Blood fluoride (ng/mL)(From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52))
- Occurrence of abnormal clinical laboratory value findings(Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks))
研究者
研究点 (38)
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