Hyperkalemia, or elevated blood potassium levels, is a potentially life-threatening condition predominantly seen in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors who have stage 3 or greater CKD, and who might have diabetes, heart failure, or both.
A randomized, single-blind, three-part Phase 3 clinical trial will evaluate RDX227675’s safety and clinical effectiveness in about 300 adult patients with CKD with or without HF, who are taking renin-angiotensin-aldosterone system inhibitors (RAASi), and have been diagnosed with hyperkalemia. The trial includes an open-label safety extension period. (In single-blind studies, only the patient is not told what medication is being given.)
An onset-of-action, single-blind, placebo controlled clinical trial (NCT03018067) will evaluate the time of onset of action in 60 patients with hyperkalemia, along with the compound’s safety. (Onset of action is the time between when a drug is administered and when a response is seen.) Results are expected by mid-2017.
“The Phase 3 study for hyperkalemia marks the start of the fifth Phase 3 clinical trial from our pipeline of internally developed, gut-restricted treatments in development,” Mike Raab, Ardelyx’s chief executive officer, said in a press release. “Hyperkalemia is a difficult to treat and potentially devastating condition in patients with chronic kidney disease and/or heart failure. The initiations of the Phase 3 and onset-of-action trials with RDX227675 are important steps forward for our cardiorenal portfolio.”
RDX227675, Ardelyx’s lead product candidate from its RDX022 program, is an oral, non-absorbed, potassium-binding polymer based on a polymer called polystyrene sulfonate.
The company in January 2016 announced positive results from an open-label clinical trial evaluating the biochemical and physiologic effects (pharmacodynamics, or PD) of RDX022 in healthy adult volunteers. The results showed that the compound efficiently binds potassium in the gastrointestinal tract, and that all the doses administered in the study (up to 27.5 g per day) were well-tolerated.
Positive results were reported in June from an expansion of the PD study. The data demonstrated that RDX227675, taken once daily, had an effect identical to dosing two or three times per day (the total daily dose was the same). The results helped establish the daily quantity that should be evaluated in clinical trials.
Ardelyx also reported that, in a randomized, single center, crossover trial that assessed various oral formulations of RDX227675 in healthy subjects, the compound was superior to sodium polystyrene sulfonate in all the taste assessments, including mouth feel, texture, and flavor.