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Study to Assess the Safety and the Phosphate Binding Capacity of Renazorb

Phase 1
Completed
Conditions
Safety
Phosphate Binding Capacity
Interventions
Drug: Renazorb 3000 mg/day
Drug: Renazorb 6000 mg/day
Drug: Renazorb 1500 mg/day
Drug: Renazorb 4500 mg/day
Registration Number
NCT01560884
Lead Sponsor
Spectrum Pharmaceuticals, Inc
Brief Summary

The purpose of this trial is to study safety, tolerability, and phosphate binding capacity of Renazorb (SPI-014) in healthy volunteers before conducting trials in patients with renal failure. Renal excretion of phosphate is expected to decrease and fecal excretion of phosphate is expected to increase after treatment.

Detailed Description

This is a double blind, dose-ranging study in healthy volunteers. Four sequential dose cohorts of 8 subjects each are planned. Six subjects will be randomly assigned to receive SPI-014 and 2 subjects to receive placebo within each cohort. The doses of SPI-014 will be 1500 mg/day (Group A), 3000 mg/day (Group B), 4500 mg/day (Group C) and 6000 mg/day (Group D), taken orally 3 times a day within 15 min after meals.

Following a screening period and evaluation of eligibility criteria, subjects will be admitted to the clinical research unit. From Day 1 to Day 10 subjects will be placed on a controlled phosphate diet (approved by a qualified dietician). From Day 1 to Day 5 (each day), 24 hour urine and feces will be collected at each voiding and pooled in separate containers for baseline phosphorus content. On Days 6 to 10, the subjects will receive SPI-014 or placebo within 15 minutes after each of the 3 main meals (see table below). From the morning of Day 8 to the morning of Day 13, 24 hour urine and feces will be collected for each day to determine phosphorus content. Subjects will be discharged on Day 13 and return 7 days later for an End-of-Study Visit on Day 20.

Starting dose will be 1500 mg/day. All safety data, including laboratory tests and adverse events, will be reviewed prior to escalation to the next cohort. After completion of first cohort, if no grades 3 AEs (vomiting and nausea) are observed in the first cohort on Day 20,Confidential 24 treatment of the second cohort begins. Similarly, third and fourth cohort will follow after the completion of the second and third cohort respectively.

Subjects will be admitted to the clinical research unit on Day -1 and remain at the clinical research unit until Day 13. From Day 1 to Day 10, subjects will consume a phosphate-controlled diet designed to provide 37.5 mmol (1200 mg) of elemental phosphorus per day (3 meals and 1 snack). The mean phosphorus contents of the meals are 12.1 mmol (387 mg), 8.6 mmol (275 mg), 12.0 mmol (416 mg), and 2.6 mmol (83 mg) for breakfast, lunch, dinner, and snack, respectively. With breakfast, the majority of the phosphorus is administered in milk. With the other meals phosphorus is primarily administered in solid food. During this 10-day treatment period subjects will be required to ingest all meals in their entirety.

The primary endpoint is phosphate binding capacity of SPI-014 as judged by levels of phosphorus in feces and urine. Phosphate excretion in urine is expected to go down and fecal excretion is expected to go up after treatment with SPI-014. Safety assessments are periodic physical examinations with vital sign measurements, safety laboratory tests, ECGs, AEs, and serious adverse events (SAEs).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
Inclusion Criteria
  • Healthy male and female volunteers ≥ 18 years of age without history of significant medical disease will be enrolled.
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group BRenazorb 3000 mg/daySix subjects will be randomly assigned to receive SPI-014 3000 mg/day dose and 2 subjects to receive placebo
Group DRenazorb 6000 mg/daySix subjects will be randomly assigned to receive SPI-014 6000 mg/day dose and 2 subjects to receive placebo
Group ARenazorb 1500 mg/daySix subjects will be randomly assigned to receive SPI-014 1500 mg/day dose and 2 subjects to receive placebo
Group CRenazorb 4500 mg/daySix subjects will be randomly assigned to receive SPI-014 4500 mg/day dose and 2 subjects to receive placebo
Primary Outcome Measures
NameTimeMethod
Efficacy6 Months

Efficacy will be evaluated by comparing difference in urine and fecal phosphorous excretion before and after treatment.

Secondary Outcome Measures
NameTimeMethod
Serum concentrations of lanthanum.30 Days
Safety6 Months

Safety will be evaluated by physical examinations, vital sign measurements, safety laboratory tests, ECGs, AEs, and serious adverse events (SAEs).

Trial Locations

Locations (1)

PAREXEL International - Baltimore Early Phase Clinical Unit

🇺🇸

Baltimore, Maryland, United States

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