A Phase1 Study to Explore the Safety of EOS789 in Patients With Chronic Kidney Disease and Hyperphosphatemia on Hemodialysis

Chugai Pharmaceutical26 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Hyperphosphatemia

Interventions

EOS789

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Safety: Incidences of adverse events

Incidences of adverse events

Time frame: Up to Day 42 in each treatment sequence

Safety: Change from baseline in vital signs

Change from baseline in vital signs (systolic blood pressure, diastolic blood pressure, pulse rate)

Time frame: Up to Day 42 in each treatment sequence

Safety: Change from baseline in clinical laboratory tests

Change from baseline in clinical laboratory tests (hematology, biochemistry, coagulation)

Time frame: Up to Day 42 in each treatment sequence

Safety: Change from baseline in 12 lead ECGs

Change from baseline in 12 lead ECGs

Time frame: Up to Day 42 in each treatment sequence

Secondary Outcomes

Pharmacokinetics: Plasma concentration of EOS789

Time frame: Day 4, 9, 10, 11 in the first treatment sequence in each period

Pharmacokinetics: Total exposure (area under the curve [AUC])

Time frame: Day 10 in the first treatment sequence in each period

Pharmacokinetics: Maximum concentration (Cmax)

Time frame: Day 10 in the first treatment sequence in each period

Pharmacokinetics: Time to reach Cmax (Tmax)

Time frame: Day 10 in the first treatment sequence in each period

Pharmacokinetics: Removal ratio of EOS789 by hemodialysis at steady state

Time frame: Day 9 in the first treatment sequence in each period

Pharmacodynamics: Intestinal fractional phosphorus absorption and accumulated fecal excretion of phosphorus

Time frame: 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

Time frame: Day 13 in the first treatment sequence and second treatment sequence in each period

A Phase1 Study to Explore the Safety of EOS789 in Patients With Chronic Kidney Disease and Hyperphosphatemia on Hemodialysis

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes