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

A Single-center, Randomized, 2-Period, Crossover, Study to Explore The Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of EOS789 in Patients With Chronic Kidney Disease and Hyperphosphatemia on Hemodialysis

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 Overview

• Status: Completed
• Conditions: Hyperphosphatemia
• Intervention / Treatment: Drug: Placebo; Drug: EOS789; Drug: Renvela

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1 Arm 1; EOS789 Dose 1 in treatment sequence 1, Placebo in treatment sequence 2	Drug: Placebo; Drug: EOS789
Experimental: Period 1 Arm 2; Placebo in treatment sequence 1, EOS789 Dose 1 in treatment sequence 2	Drug: Placebo; Drug: EOS789
Experimental: Period 2 Arm 1; EOS789 Dose 2 in treatment sequence 1, EOS789 Dose 2 + Sevelamer carbonate in treatment sequence 2	Drug: EOS789; Drug: Renvela; Other Names: Sevelamer carbonate
Experimental: Period 2 Arm 2; EOS789 Dose 2 + Sevelamer carbonate in treatment sequence 1, EOS789 Dose 2 in treatment sequence 2	Drug: EOS789; Drug: Renvela; Other Names: Sevelamer carbonate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Incidences of adverse events	Incidences of adverse events	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)	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)	Up to Day 42 in each treatment sequence
Safety: Change from baseline in 12 lead ECGs	Change from baseline in 12 lead ECGs	Up to Day 42 in each treatment sequence

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Leader, Chugai Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: November 11, 2016
• First Submitted That Met QC Criteria: November 11, 2016
• First Posted (Estimate): November 16, 2016

Study Record Updates

• Last Update Posted (Actual): September 13, 2018
• Last Update Submitted That Met QC Criteria: September 12, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Phosphorus Metabolism Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Hyperphosphatemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Sevelamer
• Other Study ID Numbers: EOS103US