Clinical trial NCT02965053: A Phase1 Study to Explore the Safety of EOS789 in Patients With Chronic Kidney Disease and Hyperphosphatemia on Hemodialysis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperphosphatemia
Lead sponsor: Chugai Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2016-11-16
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Safety: Incidences of adverse events
timeFrame: Up to Day 42 in each treatment sequence
measure: Safety: Change from baseline in vital signs
timeFrame: Up to Day 42 in each treatment sequence
measure: Safety: Change from baseline in clinical laboratory tests
timeFrame: Up to Day 42 in each treatment sequence
measure: Safety: Change from baseline in 12 lead ECGs
timeFrame: Up to Day 42 in each treatment sequence
Secondary outcomes:
measure: Pharmacokinetics: Plasma concentration of EOS789
timeFrame: Day 4, 9, 10, 11 in the first treatment sequence in each period
measure: Pharmacokinetics: Total exposure (area under the curve [AUC])
timeFrame: Day 10 in the first treatment sequence in each period
measure: Pharmacokinetics: Maximum concentration (Cmax)
timeFrame: Day 10 in the first treatment sequence in each period
measure: Pharmacokinetics: Time to reach Cmax (Tmax)
timeFrame: Day 10 in the first treatment sequence in each period
measure: Pharmacokinetics: Removal ratio of EOS789 by hemodialysis at steady state
timeFrame: Day 9 in the first treatment sequence in each period
measure: Pharmacodynamics: Intestinal fractional phosphorus absorption and accumulated fecal excretion of phosphorus
timeFrame: Days 11 to 13 in the first treatment sequence and second treatment sequence in each period
measure: 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
timeFrame: Day 13 in the first treatment sequence and second treatment sequence in each period
Other outcomes:
Locations:
city: Indianapolis
country: United States
state: Indiana
Study officials:
affiliation: Chugai Pharmaceutical
name: Clinical Leader
role: STUDY_DIRECTOR
References: