Hyperphosphatemia
Conditions
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.
Interventions
Sponsors
Chugai Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Incidences of adverse events | Up to Day 42 in each treatment sequence | Incidences of adverse events |
| 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) |
| Safety: Change from baseline in 12 lead ECGs | Up to Day 42 in each treatment sequence | Change from baseline in 12 lead ECGs |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Removal ratio of EOS789 by hemodialysis at steady state | Day 9 in the first treatment sequence in each period |
| Pharmacokinetics: Plasma concentration of EOS789 | Day 4, 9, 10, 11 in the first 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 |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed