A Phase1 Study to Explore the Safety of EOS789 in Patients With Chronic Kidney Disease and Hyperphosphatemia on Hemodialysis
- Registration Number
- NCT02965053
- Lead Sponsor
- Chugai Pharmaceutical
- Brief Summary
This study is a randomized study designed as a 2x2 cross-over in two periods (Period 1 and Period 2) to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of EOS789 in patients with chronic kidney disease (CKD) and hyperphosphatemia receiving hemodialysis. Period 1 is double-blind and Period 2 is open-label. Period 1 and Period 2 are identical with regard to the design, inclusion/exclusion criteria, and assessments. EOS789 and its combination with sevelamer carbonate are tested in Period 1 and Period 2 respectively.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
Inclusion Criteria
- Patients with CKD and hyperphosphatemia must meet the following criteria for study entry:
- Age ≥18 years
- On thrice-weekly hemodialysis for at least 3 months prior to screening
- Not having changed dialysis prescription within 4 weeks prior to screening for dialyzer, calcium concentration in dialysate, or dry weight more than 1 kg
- Receiving stable doses of treatments affecting serum phosphorus for at least 4 weeks prior to screening and willing to discontinue these treatments
Exclusion Criteria
- Patients with CKD and hyperphosphatemia who meet any of the following criteria will be excluded from study entry:
- Uncontrolled diabetes and/or hypertension in the opinion of the investigators
- Uncontrolled chronic constipation and/or diarrhea in the opinion of the investigators
- Hospitalization for cardiac disease in previous 3 months
- Evidence of acute or chronic hepatitis or known liver cirrhosis
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Period 1 Arm 1 EOS789 EOS789 Dose 1 in treatment sequence 1, Placebo in treatment sequence 2 Period 1 Arm 1 Placebo EOS789 Dose 1 in treatment sequence 1, Placebo in treatment sequence 2 Period 1 Arm 2 EOS789 Placebo in treatment sequence 1, EOS789 Dose 1 in treatment sequence 2 Period 1 Arm 2 Placebo Placebo in treatment sequence 1, EOS789 Dose 1 in treatment sequence 2 Period 2 Arm 1 EOS789 EOS789 Dose 2 in treatment sequence 1, EOS789 Dose 2 + Sevelamer carbonate in treatment sequence 2 Period 2 Arm 1 Renvela EOS789 Dose 2 in treatment sequence 1, EOS789 Dose 2 + Sevelamer carbonate in treatment sequence 2 Period 2 Arm 2 Renvela EOS789 Dose 2 + Sevelamer carbonate in treatment sequence 1, EOS789 Dose 2 in treatment sequence 2 Period 2 Arm 2 EOS789 EOS789 Dose 2 + Sevelamer carbonate in treatment sequence 1, EOS789 Dose 2 in treatment sequence 2
- Primary Outcome Measures
Name Time Method Safety: Incidences of adverse events Up to Day 42 in each treatment sequence Incidences of adverse events
Safety: Change from baseline in 12 lead ECGs Up to Day 42 in each treatment sequence Change from baseline in 12 lead ECGs
Safety: Change from baseline in vital signs Up to Day 42 in each treatment sequence Change from baseline in vital signs (systolic blood pressure, diastolic blood pressure, pulse rate)
Safety: Change from baseline in clinical laboratory tests Up to Day 42 in each treatment sequence Change from baseline in clinical laboratory tests (hematology, biochemistry, coagulation)
- Secondary Outcome Measures
Name Time Method Pharmacokinetics: Plasma concentration of EOS789 Day 4, 9, 10, 11 in the first treatment sequence in each period Pharmacokinetics: Total exposure (area under the curve [AUC]) Day 10 in the first treatment sequence in each period Pharmacokinetics: Maximum concentration (Cmax) Day 10 in the first treatment sequence in each period Pharmacokinetics: Time to reach Cmax (Tmax) Day 10 in the first treatment sequence in each period Pharmacokinetics: Removal ratio of EOS789 by hemodialysis at steady state Day 9 in the first treatment sequence in each period Pharmacodynamics: Intestinal fractional phosphorus absorption and accumulated fecal excretion of phosphorus Days 11 to 13 in the first treatment sequence and second treatment sequence in each period Efficacy: Change from baseline of serum phosphorus (P), Calcium (Ca), Ca x P, intact parathyroid hormone (PTH), and fibroblast growth factor (FGF23) at Day 13 Day 13 in the first treatment sequence and second treatment sequence in each period