Exploratory Study of ZG-801 for the Treatment of Hyperkalemia

ZG-801 Phase II Trial - Exploratory Study of Efficacy and Safety on Patients With Hyperkalemia, and Long Term Safety Study -

To investigate the efficacy of each ZG-801 starting dose and the titration algorithm of ZG-801 for the treatment of hyperkalemia in Japanese patients.

To evaluate the safety of ZG-801 for the chronic use (total over 52 weeks). In addition, to confirm the safety after the discontinuation of ZG-801 treatment on 1 week follow-up.

Study Overview

• Status: Completed
• Conditions: Hyperkalemia
• Intervention / Treatment: Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: patiromer; Drug: placebo; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kanagawa, Japan
    • Zeria Investigative Sites

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females ages 18 - 80
• Informed consent given
• Serum Potassium measurement at baseline is 5.1 to < 6.5 mEq/L (Non-dialysis patients or 5.5 to < 6.5 mEq/L (Dialysis patients)

Exclusion Criteria:

• Subjects with hospitalization for hyper- or hypoglycemia with Type 2 diabetes or for acute exacerbations of heart failure within the previous 3 months
• Subjects with severe heart failure, defined as NYHA (New York Heart Association) class IV
• Subjects with uncorrected hemodynamically significant primary vascular disease or uncontrolled or hemodynamically unstable arrhythmia
• Subjects with coronary artery bypass graft, percutaneous intervention, or major surgery including thoracic and cardiac, within the previous 3 months or anticipated need during study participation
• Subjects with heart, liver (only Dialysis patients), or kidney transplant recipient, or anticipated need for transplant during the study period
• Subjects with any of the significant cardiovascular or cerebrovascular events within the previous 2 months
• Subjects with a history of or current diagnosis of a severe swallowing disorder, moderate to severe gastroparesis, or history of bariatric surgery, bowel obstruction or severe gastrointestinal disorders or major gastrointestinal surgery
• Subjects who cannot use the oral concomitant medication to be separate 3 hours from ZG-801 medication
• Subjects suspected of transient high potassium levels, such as those caused only by dietary effects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stratum 1: 8.4 g patiromer; Non-dialysis subjects with serum potassium 5.1 to < 6.0 mEq/L range at baseline	Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3)
Experimental: Stratum 1: 16.8 g patiromer; Non-dialysis subjects with serum potassium 5.1 to < 6.0 mEq/L range at baseline	Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3)
Experimental: Stratum 1: placebo of 8.4 g patiromer; Non-dialysis subjects with serum potassium 5.1 to < 6.0 mEq/L range at baseline	Drug: placebo; Placebo starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: placebo; Placebo starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1)
Experimental: Stratum 1: placebo of 16.8 g patiromer; Non-dialysis subjects with serum potassium 5.1 to < 6.0 mEq/L range at baseline	Drug: placebo; Placebo starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: placebo; Placebo starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1)
Experimental: Stratum 2: 8.4 g patiromer; Non-dialysis subjects with serum potassium 6.0 to < 6.5 mEq/L range at baseline	Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3)
Experimental: Stratum 2: 16.8 g patiromer; Non-dialysis subjects with serum potassium 6.0 to < 6.5 mEq/L range at baseline	Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3)
Experimental: Stratum 3: 8.4 g patiromer; Dialysis subjects with serum potassium 5.5 to < 6.5 mEq/L range at baseline	Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3)
Experimental: Stratum 3: 16.8 g patiromer; Dialysis subjects with serum potassium 5.5 to < 6.5 mEq/L range at baseline	Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2); Drug: patiromer; Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3); Drug: patiromer; Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in serum potassium from baseline to 1 week after the start of administration in each group of starting dose	Baseline to week 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in serum potassium 4 weeks after the start of administration in each group of starting dose	Baseline to week 4
Proportion of subjects with a normalized serum potassium level at 4 weeks after the start of administration in each group of starting dose	Week 4
Incidence of adverse events	Over 52-week study period
Incidence of adverse drug reactions	Over 52-week study period

Collaborators and Investigators

• Sponsor: Zeria Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2019
• Primary Completion (Actual): November 6, 2019
• Study Completion (Actual): February 2, 2021

Study Registration Dates

• First Submitted: January 8, 2019
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia
• Other Study ID Numbers: ZG-801-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No