A Study to Investigate the Safety and Efficacy of ZS in P... | NCT02875834

NCT02875834

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sodium Zirconium Cyclosilicate (ZS) 5g	Experimental	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.	Drug: Sodium Zirconium Cyclosilicate (ZS) 5g
Sodium Zirconium Cyclosilicate (ZS) 10g	Experimental	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.	Drug: Sodium Zirconium Cyclosilicate (ZS) 10g
Placebo	Placebo Comparator	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sodium Zirconium Cyclosilicate (ZS) 10g	Drug	Suspension administered 10g orally three times per day, in the first 48-hour of the study for all patients (48-hour open label initial phase)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Least Square Mean S-K Level on Days 8-29	Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29. The results in the table below are presented for RTP.	Through 28-day randomized treatment study phase day 8-29.

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Patients Achieving Normokalemia	Proportion of patients who achieve normokalemia during the initial phase at 24 and 48 hours. The results in the table below are presented for OLP. (h=hours).	Through 48-hour initial phase.
Exponential Rate of Change in S-K Levels

Eligibility Module

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Chiba		260-8712	Japan
Research Site

References Module

Label	URL
Related Info	View source
Related Info	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
FG001	Sodium Zirconium Cyclosilicate (ZS) 5g

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Mar 15, 2018	Feb 11, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Sodium Zirconium Cyclosilicate (ZS) 10g

Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.

In RTP there were no subjects analyzed in Sodium Zirconium Cyclosilicate (ZS) 10g tid arm. In OLP, only ZS 10 g TID arm was present. All subjects in RTP took part in OLP.

Arm/Group Information

ID	Title	Description
BG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
BG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
BG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
BG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

All subjects in RTP took part in OLP. Thus, the Totals are calculated using replicated measurements.

RTP: For the 28-day randomized treatment study phase, the Full Analysis Set (FAS) will include all patients who are randomized to the 28-day randomized treatment study phase.

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00067.8± 10.80 BG00166.7± 11.40 BG00268.0± 10.18 BG003

Sex: Female, Male

All subjects in RTP took part in OLP. Thus, the Totals are calculated using replicated measurements.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00096 BG00136 BG002

Ethnicity (NIH/OMB)

All subjects in RTP took part in OLP. Thus, the Totals are calculated using replicated measurements.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0002 BG0010 BG002

Race (NIH/OMB)

All subjects in RTP took part in OLP. Thus, the Totals are calculated using replicated measurements.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010

Country

All subjects in RTP took part in OLP. Thus, the Totals are calculated using replicated measurements.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Japan	BG00068 BG00126 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Least Square Mean S-K Level on Days 8-29

Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Least Squares Mean

95% Confidence Interval

mmol/L

Through 28-day randomized treatment study phase day 8-29.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Units	Counts
Participants	OG0000 OG00199 OG00299 OG003

Title

Denominators

Categories

Title	Measurements
	OG0014.811(4.685 to 4.940) OG0024.381(4.265 to 4.501) OG0035.321(5.155 to 5.493)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG003	Results derived from a mixed effects model of log-transformed S-K levels. Fixed effects are: treatment group; visit; treatment-by-visit interaction; baseline S-K values (OLP and RTP); baseline eGFR; age category; country; baseline RAAS inhibitor, chronic kidney disease, heart failure, and diabetes mellitus statuses. Patient is a random effect. p-values given are for differences of LSMEANS. The back-transformation is to the original scale of the S-K measurement.	Mixed Models Analysis		<0.001		Mean Difference (Final Values)	0.904			2-Sided	95	0.876	0.933					Other

Secondary

Proportion of Patients Achieving Normokalemia

Proportion of patients who achieve normokalemia during the initial phase at 24 and 48 hours. The results in the table below are presented for OLP. (h=hours).

Full Analysis Set

Posted

Number

Participants

Through 48-hour initial phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Exponential Rate of Change in S-K Levels

Exponential rate of change in S-K levels (blood) during the 48-hour open-label initial phase. The results in the table below are presented for OLP.

Full Analysis Set

Posted

Mean

Standard Error

log(mmol/L)/h

Through 48-hour initial phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Absolute Change From Baseline in S-K Levels

Absolute change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.

Full Analysis Set

Posted

Mean

Standard Deviation

mmol/L

Through 48-hour initial phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Percentage Change From Baseline in S-K Levels

Percentage change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.

Full Analysis Set

Posted

Mean

Standard Deviation

Percentage change

Through 48-hour initial phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Proportion of Patients Remaining Normokalemic

The proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at the end of the 28-day randomized treatment study phase and during the 28-day randomized treatment study phase. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Number

Participants

Through 28-day randomized treatment study phase day 8-29.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit

The proportion of patients who are normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at Day 1 through Day 29/Exit in randomization phase. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Number

Participants

Through 28-day randomized treatment phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Days Patients Remain Normokalemic

The number of days patients remain normokalemic during the 28-day randomized treatment study phase. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Least Squares Mean

Standard Error

Day

Through 28-day randomized treatment phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Mean Change in S-K Levels

The mean change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Mean

Standard Deviation

mmol/L

Through 28-day randomized treatment phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Mean Percentage Change in S-K Levels

The mean percentage change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Mean

Standard Deviation

Percentage change

Through 28-day randomized treatment phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Number of Hyperkalemic Patients

The results represent number of hyperkalemic patients during the 28-day randomized treatment study phase. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Count of Participants

Participants

Through 28-day randomized treatment phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Mean Changes in S-Aldosterone and P Renin Levels

The mean changes from OLP baseline in S-Aldosterone and P-Renin levels. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Mean

Standard Deviation

pmol/L

Through 28-day randomized treatment phase.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Secondary

Patient Reported Health State (EQ-5D) Questionnaire

Evaluate health state of patients using EQ-5D questionnaire. This scale is numbered from 0 to 100. 0 means the worst health you can imagine. 100 means the best health you can imagine. The results in the table below are presented for RTP.

Full Analysis Set

Posted

Mean

Standard Deviation

Units on a scale

Through study completion, an average of 37 days.

ID	Title	Description
OG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
OG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
OG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
OG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sodium Zirconium Cyclosilicate (ZS) 10g Tid	Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.	267	0	267	0	267
EG001	Sodium Zirconium Cyclosilicate (ZS) 5g	Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.	99	4	99	6	99
EG002	Sodium Zirconium Cyclosilicate (ZS) 10g	Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.	99	3	99	21	99
EG003	Placebo	Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.	50	1	50	0	50

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Cystitis	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0010 events0 affected99 at risk EG0021 events1 affected99 at risk EG0030 events0 affected50 at risk
Infectious colitis	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0011 events1 affected99 at risk EG0020 events0 affected99 at risk EG003
Pneumonia	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0011 events1 affected99 at risk EG0020 events0 affected99 at risk EG003
Upper respiratory tract infection	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0010 events0 affected99 at risk EG0021 events1 affected99 at risk EG003
Cardiac failure	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0010 events0 affected99 at risk EG0021 events1 affected99 at risk EG003
Cardiac failure congestive	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0011 events1 affected99 at risk EG0020 events0 affected99 at risk EG003
Hypertension	Vascular disorders	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0011 events1 affected99 at risk EG0020 events0 affected99 at risk EG003
Gastritis	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0011 events1 affected99 at risk EG0020 events0 affected99 at risk EG003
Renal impairment	Renal and urinary disorders	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0010 events0 affected99 at risk EG0021 events1 affected99 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0010 events0 affected99 at risk EG0020 events0 affected99 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Oedema peripheral	General disorders	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0014 events4 affected99 at risk EG0027 events7 affected99 at risk EG0030 events0 affected50 at risk
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0011 events1 affected99 at risk EG0029 events9 affected99 at risk EG003
Oedema	General disorders	Non-systematic Assessment	EG0000 events0 affected267 at risk EG0011 events1 affected99 at risk EG0029 events8 affected99 at risk EG003

ID	Term
D006947	Hyperkalemia

ID	Term
C000597310	sodium zirconium cyclosilicate

Units	Counts
Participants	OG0000 OG00199 OG00299 OG00350

Title	Measurements
	OG000-0.81± 0.398

Title	Measurements
	OG000-1.28± 0.499

Title	Measurements
	OG00189 OG00293 OG00340

Title	Measurements
	OG00171 OG00289 OG00327

Title	Measurements
	OG00162 OG00281 OG00316

Title	Measurements
	OG00162 OG00278 OG00312

Title	Measurements
	OG00157 OG00277 OG00312

Title	Measurements
	OG00155 OG00276 OG00311

Title	Measurements
	OG00154 OG00273 OG00311

Title	Measurements
	OG00156 OG00274 OG0038

Title	Measurements
	OG00151 OG00271 OG00311

Title	Measurements
	OG00158 OG00277 OG00312

Title	Measurements
	OG0010.92± 0.661 OG0020.77± 0.695 OG0030.88± 0.684

Title	Measurements
	OG001-91.75± 179.791 OG002-96.37± 108.002 OG00339.78± 152.050

Title	Measurements
	OG001-102.70± 212.187 OG002-90.22± 91.149 OG00341.07± 198.266

Title	Measurements
	OG001-0.23± 1.158 OG002-0.26± 1.913 OG003-0.30± 1.031

Title	Measurements
	OG001-0.39± 1.350 OG002-1.09± 4.732 OG0030.60± 3.250

Title	Measurements
	OG001-0.27± 1.008 OG002-1.56± 4.165 OG003-0.25± 2.725

Title	Measurements
	OG00177.6± 16.50 OG00276.9± 16.08 OG00376.6± 14.08

ID	Term
D014883	Water-Electrolyte Imbalance
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases