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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hyperphosphatemia

Intervention / Treatment
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* Drug: EOS789
* Drug: Placebo
* Drug: Renvela


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1 Arm 1<br>EOS789 Dose 1 in treatment sequence 1, Placebo in treatment sequence 2 | Drug: EOS789<br> <br> Drug: Placebo<br> <br> |
| Experimental: Period 1 Arm 2<br>Placebo in treatment sequence 1, EOS789 Dose 1 in treatment sequence 2 | Drug: EOS789<br> <br> Drug: Placebo<br> <br> |
| Experimental: Period 2 Arm 1<br>EOS789 Dose 2 in treatment sequence 1, EOS789 Dose 2 + Sevelamer carbonate in treatment sequence 2 | Drug: EOS789<br> <br> Drug: Renvela<br> <br> * Other names: Sevelamer carbonate;|
| Experimental: Period 2 Arm 2<br>EOS789 Dose 2 + Sevelamer carbonate in treatment sequence 1, EOS789 Dose 2 in treatment sequence 2 | Drug: EOS789<br> <br> Drug: Renvela<br> <br> * Other names: Sevelamer carbonate;|

What is the study measuring?
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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 | Measure Description | 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 |