Safety & Efficacy of Zirconium Silicate in Chronic Kidney Disease or Moderate Kidney Dysfunction With Mild Hyperkalemia
Chronic Kidney Disease
Drug: Zirconium silicate (ZS)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
|Official Title:||Multicenter, Prospective, Randomized, Placebo-Controlled, Double-blind Dose Escalating Study of Safety, Tolerability and Pharmacodynamics of Zirconium Silicate in Chronic Kidney Disease and Moderate Kidney Dysfunction With Mild Hyperkalemia|
- Change in serum potassium levels from baseline after administration of zirconium silicate three times a day. [ Time Frame: during the first 48 hours ] [ Designated as safety issue: Yes ]To evaluate the effect on serum potassium (S-K)) of 3 different doses of zirconium silicate (ZS) administered 3 times daily for 48 hours (with up to an additional 48 hours of three times a day dosing for subjects whose S-K has not normalized [3.5 - 4.9 mmol/l] after the initial 48 hours) to subjects with moderate Chronic Kidney Disease (CKD as defined by a glomerular filtration rate (GFR) between 40-60ml/min) and mild hyperkalemia (S-K between 5-6.0 mmol/l).
- Identify optimal zirconium silicate dose to normalize serum potassium levels between 3.5 - 4.9 mmol/L without causing serious adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2011|
|Study Completion Date:||June 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Experimental: Zirconium silicate (ZS)
Randomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated, microporous zirconium silicate, an oral sorbent) administered 3 times (tid) daily with meals.
Drug: Zirconium silicate (ZS)
Randomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated microporous Zirconium Silicate, an oral sorbent) administered 3 times (tid) daily with meals.
Other Name: ZS-9
Placebo Comparator: Placebo
Placebo ( Silicified microcrystalline cellulose) randomized to mimic escalating doses of experimental drug administered 3 times (tid) daily with meals.
Randomized to mimic escalating doses of experimental drug administered 3 times (tid) daily with meals.
Other Name: silicified microcrystalline cellulose
A total of 90 subjects with moderate CKD (defined as GFR between 40- 60ml/min) and mild hyperkalemia (S-K between 5-6 mmol/l) will be enrolled in the study where, in a double-blind dose-escalating fashion (three separate cohorts), they will be randomized to receive one of the doses of ZS (0.3g, 3g and 10g) or placebo, administered 3 times (tid) daily with meals. The first cohort will have 18 subjects while both of the second and third cohorts will have 36 subjects for a total of 90 subjects.
Safety and tolerability will be assessed by an Independent Data Safety Monitoring Board (DSMB) after completion of each cohort, before escalation to the next dose level will be allowed. The next dose escalation will happen no sooner than one week after the last dose of study drug at the previous dosing level has been administered. Safety stopping rules will be specified for this study. Within the first dose level (300 mg dose), 12 subjects will be randomized to receive ZS, whereas 6 subjects will be randomized to receive placebo for a total of 18 subjects in this first cohort. In the next two cohorts (3 g and 10 g doses), 24 subjects per cohort will be randomized to receive ZS, whereas 12 subjects per cohort will be randomized to receive placebo for a total of 36 subjects in each of the second and third cohorts.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01493024
|United States, Arizona|
|Southwest Clinical Research Institute|
|Tempe, Arizona, United States, 85284|
|United States, California|
|West Coast Clinical Trials|
|Costa Mesa, California, United States, 92626|
|United States, Florida|
|Riverside Clinical Research|
|Edgewater, Florida, United States, 32132|
|Elite Research Institute, Inc.|
|Miami, Florida, United States, 33169|
|Compass Research Phase 1, LLC|
|Orlando, Florida, United States, 32806|
|Lakeview Medical Research|
|Summerfield, Florida, United States, 34491|
|United States, Kansas|
|Johnson County Clin-Trials|
|Lenexa, Kansas, United States, 66219|
|United States, Texas|
|Southwest Houston Research, Ltd|
|Houston, Texas, United States, 77099|
|Renal Associates, P.A.|
|San Antonio, Texas, United States, 78215|
|Study Chair:||Henrik Rasmussen, MD||ZS Pharma, Inc.|