Intervention
SAID
Patients were administered tenapanor orally, twice-daily, immediately before meals during the treatment period. It was suggested that patients should consume a normal diet (i.e., without restricting phosphorus), and any changes in the diet from the screening day were prohibited. The study drug starting dose was 5 mg, and the dose was adjusted in the range of 5, 10, 20, and 30 mg per dose in a stepwise manner. The dose was escalated if the serum phosphorus level was ≥ 6.1 mg/dL; or if the serum phosphorus level was ≤ 6.0 mg/dL, in which case the investigators considered that it was appropriate to increase the dose until the serum phosphorus level reached approximately 4.5 mg/dL, and the investigators considered that a dose increase would not pose safety concerns for patients. Conversely, the dose was reduced if the serum phosphorus level was < 3.5 mg/dL or if the investigators judged that the dose should be reduced because of drug-related AEs. Dose adjustments (i.e., increase, reduction, or discontinuation) were made at patient visits, which took place every 2 weeks. Each dose adjustment was performed immediately before meals, based on the serum phosphorus level (measured at the investigative site) and safety.Drugs that may affect serum phosphorus levels were prohibited for concomitant use from the washout period to the end of week 8. If the investigator judged that the tolerable dose of tenapanor was insufficient to reduce serum phosphorus levels after completing the week 8 evaluation, rescue treatment with a phosphate binder was allowed. The investigator selected one phosphate binder from the drugs used before washout, and administration was initiated at the starting dose specified in the package insert of said phosphate binder. Rescue treatment was initiated when all phosphate binder administration criteria were met. Only one type of phosphate binder could be used in combination with tenapanor. Additionally, changing the type of phosphate binder chosen for rescue treatment was not allowed. Concomitant use of phosphate binders at or after week 8 could be initiated if the following criteria were met and the investigator considered it was needed as rescue treatment: the tenapanor dose was 30 mg or could not be further increased because of a study drug-related treatment-emergent AE (TEAE); the serum phosphorus level was ≥ 6.1 mg/dL at the scheduled visit after the continuous administration of tenapanor at the same dose for ≥ 1 week and the investigator considered that a further dose increase could compromise patient safety; and the investigator considered that concomitant use of phosphate binders would not compromise patient safety.