A Phase 2b, Randomized, Double blind, Placebo-controlled, Parallel group, Multicentre Dose finding Study to evaluate the Efficacy, Safety and Tolerability of AZD1722 to Treat Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)

INTERVENTION: Product Name: AZD1722 tablet 1 mg Product Code: AZD1722 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: tenapanor (INN Modified: tenapanor dihydrochloride) CAS Number: 1234365‐97‐9 Current Sponsor code: AZD1722 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: AZD1722 tablet 3 mg Product Code: AZD1722 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: tenapanor (INN Modified: tenapanor dihydrochloride) CAS Number: 1234365‐97‐9 Current Sponsor code: AZD1722 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 3‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: AZD1722 tablet 10 mg Product Code: AZD1722 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: tenapanor (INN Modified: tenapanor dihydrochloride) CAS Number: 1234365‐97‐9 Current Sponsor code: AZD1722 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: AZD1722 tablet 30 mg Product Code: AZD1722 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: tenapanor (INN Modified: tenapanor dihydrochloride) CAS Number: 1234365‐97‐9 Current Sponsor code: AZD1722 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 30‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Hyperphosphatemia in patients with end‐stage renal disease on hemodialysis. ; MedDRA version: 16.1 Level: LLT Classification code 10020712 Term: Hyperphosphatemia System Organ Class: 100000004861 Therapeutic area: Diseases [C] ‐ Nutritional and Metabolic Diseases [C18] PRIMARY OUTCOME: Main Objective: 1. Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment. Primary end point(s): 1. Change in serum phosphate levels Secondary Objective: 1. To characterize the dose response relationship of AZD1722 on serum phosphate levels; 2. To compare the effect of AZD1722 versus pre wash out phosphate‐lowering treatment, by comparing serum phosphate levels during AZD1722 treatment to pre wash out levels; 3. To compare the effect of AZD1722 versus placebo on the number of patients reaching serum phosphate goal levels defined as < 5.5 mg/dl (1.78 mmol/L) during 4 weeks of treatment; 4. To compare the effect of AZD1722 versus placebo on the change in serum calcium x phosphate product from end of wash out (pre randomization value) to end of treatment ; 5. To evaluate the safety and tolerability of AZD1722 as assessed by adverse event recording, vital signs, 12‐lead electrocardiogram, physical examination, and safety laboratory monitoring; Timepoint(s) of evaluation of this end point: 1. End of wash‐out (pre randomization value) to end of treatment; SECONDARY OUTCOME: Secondary end point(s): 1. Dose response relationship ; 2. Change from pre wash‐out in S‐phosphate levels ; 3. The number of patients reaching S‐phosphate goal ; 4. Change from baseline in calcium x phosphate product ; 5. Safety and tolerability of AZD1722 ; Timepoint(s) of evaluation of this end point: 1. End of wash‐out (pre randomization value) to end of treatment ; 2. Pre wash‐out to end of treatment ; 3. End of wash‐out (pre randomization value) to end of treatment ; 4. End of wash‐out (pre randomization value) to end of treatment ; 5. End of wash‐out (pre randomization value) to end of treatment INCLUSION CRITERIA: 1. Females and males aged =18 years 2. Chronic maintenance hemodialysis 3 x/week for a at least 3 months 3. Prescribed and taking at least 3 doses of phosphate binder per day 4. Serum phosphate levels should be between 3.5 and 8.0 mg/dL (inclusive) at screening 5. Total serum calcium levels 2.0 ‐ 2.6 mmol/L inclusive at screening 6. For randomization in the study, after up to 3 weeks wash out of phosphate binders, patients must have serum phosphate levels of at least 6. 0 mg/dL (1.94 mmol/L) but below 10 mg/dL (3.23 mmol/L) and have had an increase of at least 1.5 mg/dL (0.48 mmol/L) vs pre wash out. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150