A Two-Part, Phase 3 Study Evaluating the Efficacy and Safety of WS016 for the Treatment of Hyperkalemia

Официальное название

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Clinical Study to Evaluate the Efficacy and Safety of WS016 in Patients With Hyperkalemia

Обзор

This clinical trial consists of 2 parts, Part A and Part B. Part A consists of a 2-day randomized, double-blind, placebo-controlled corrective phase (CP) and a 28-day randomized, double-blind, placebo-controlled maintenance phase (MP). Part B (open-label extension, OLE) is an open-label, 11-month extension study carried out in participants who come from Part A and meet certain inclusion criteria.

Подробное описание

Eligible participants with hyperkalemia will first be randomized in a 5:1 ratio to receive oral WS016 (12g) or placebo three times daily, for a total of six doses over 48 hours.

After the 48-hour corrective treatment, participants whose serum potassium is within the normal range will be re-randomized in a 1:1:1:1 ratio to receive oral WS016 (6g, 12g, or 18g) or placebo once daily for 28 consecutive days.

Participants who complete the 28-day maintenance phase or prematurely discontinue from it due to hyperkalemia or hypokalemia, and who meet the eligibility criteria, will be eligible to enter Part B. In Part B, participants will receive WS016 for 11 months, starting at 12g once daily, with subsequent dose adjustments based on serum potassium levels.

Вмешательства

• Препарат WS016
  WS016 (12g), oral, three times daily for 48 hours, for a total of six doses.
• Препарат Placebo
  Placebo, oral, three times daily for 48 hours, for a total of six doses.
• Препарат WS016
  WS016 (6g, 12g or 18g), oral, once daily for 28 consecutive days.
• Препарат Placebo
  Placebo, oral, once daily for 28 consecutive days.
• Препарат WS016
  WS016, oral, once daily for 11 months, starting at a dose of 12g with subsequent dose adjustments based on serum potassium levels.

Первичные конечные точки

• Mean serum potassium level during maintenance phase Days 8-29 [Срок оценки: Maintenance phase Days 8-29]

Вторичные конечные точки (5)

• Exponential rate of change in serum potassium during the corrective phase [Срок оценки: Through 48 hours corrective phase]
• Mean change from baseline in serum potassium at all time points of corrective phase [Срок оценки: Through 48 hours corrective phase]
• Cumulative duration (in days) of serum potassium within the normal range during the maintenance phase [Срок оценки: Maintenance phase baseline to maintenance phase Day 29]
• Mean change from baseline in serum potassium at all time points of maintenance phase [Срок оценки: Through 28 days maintenance phase]
• Percentage of participants with the mean serum potassium ≤5.0 mmol/L and percentage of participants with the mean serum potassium ≤5.5 mmol/L from D8 to D337 of the open-label extension phase [Срок оценки: Open-label extension phase Days 8-337]

Критерии участия

Критерии включения

• Adults (male or female) aged 18 years and older;
• Participants with a serum potassium concentration >5.0 mmol/L and ≤6.5 mmol/L (serum potassium concentration will be measured using the i-STAT portable biochemical analyzer in screening period);
• Participants who have negative pregnancy test result at screening and ensure the use of contraception during the trial;
• Participants who understand and voluntarily sign the Informed Consent Form.

Критерии исключения

• Participants who have a history of severe drug allergy, or are definitely allergic to the investigational product or its ingredients;
• Participants who have pseudohyperkalemia, such as serum potassium increasing caused by hemolysis of blood samples due to improper blood collection methods (such as too tight pressure pulse band banding, too heavy local rubbing, repeated fist clenching-loosening hands), hemolysis of blood samples due to difficulty in venipuncture or trauma, and severe leukocytosis (>50 × 10\^9/L) or thrombocytosis (>500 × 10\^9/L);
• Participants with acute hyperkalemia caused by conditions such as tumor lysis syndrome or hemolysis and so on;
• Participants suffering from severe cerebrovascular diseases, such as cerebral infarction or cerebral hemorrhagic disease, with language disorder or unresponsiveness, or severely blocked limb movement;
• Participants who have suffered from myocardial infarction, or have undergone interventional cardiac procedures or coronary artery bypass grafting for coronary atherosclerotic heart disease within 3 months prior to screening; or participants who have heart failure and are in cardiac function class IV (New York Heart Association, NYHA classification criteria) at screening;
• Participants with cardiac arrhythmia requiring urgent treatment at screening, such as ventricular tachycardia, ventricular fibrillation, II-III degree atrioventricular block, severe bradycardia (heart rate <40 bpm), or participants with significant prolongation of PR interval (PR interval prolonged to more than 0.25 seconds in the absence of pre-existing atrioventricular block), decrease or disappearance of P wave amplitude, and widening of QRS wave (widening to more than 0.14 seconds in the absence of pre-existing bundle branch block) indicated by the electrocardiogram at screening;
• Participants who have previously undergone major gastrointestinal surgery such as subtotal gastrectomy, short bowel syndrome and other diseases affecting the normal peristalsis of the gastrointestinal tract; or participants with intractable constipation;
• Participants who have received treatment with polypropylene exchange resin or sodium zirconium cyclosilicate and other similar drugs within 3 days before screening;
• Participants who participated in other clinical trials of drugs or devices not approved for marketing within 3 months prior to the first dose;
• Participants who are receiving dialysis;
• Participants with severe hepatic impairment: serum alanine aminotransferase or aspartate aminotransferase more than 3 times the upper limit of normal;
• Participants who are unable to complete this part of the trial as assessed by the investigator due to any other disease or psychiatric condition; or participants whose participation in the trial is assessed by the investigator as having a risk that far outweighs the benefit.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 50 центров

• Investigator Site 02 — Bengbu
• Investigator Site 03 — Wuhu
• Investigator Site 48 — Чунцин
• Investigator Site 04 — Xiamen
• Investigator Site 05 — Lanzhou
• Investigator Site 07 — Гуанчжоу
• Investigator Site 06 — Zhanjiang
• Investigator Site 08 — Huizhou
• … и ещё 42 центра

Идентификаторы

NCT: NCT07251309 · WS016CT301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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