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

Waterstone Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Hyperkalemia

Treatments: Drug: WS016; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07251309

WS016CT301

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 420 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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420 participants in 5 patient groups, including a placebo group

WS016 (corrective phase)

Experimental group

Treatment:

Drug: WS016

Drug: WS016

Drug: WS016

Placebo (corrective phase)

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

WS016 (maintenance phase)

Experimental group

Treatment:

Drug: WS016

Drug: WS016

Drug: WS016

Placebo (maintenance phase)

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

WS016 (open-label extension phase)

Experimental group

Treatment:

Drug: WS016

Drug: WS016

Drug: WS016