The Effect of Sodium Zirconium Cyclosilicate on Albuminuria in Patients With Type 2 Diabetes and Hyperkalemia (ZIRCUS)

A Randomized, Double-blind, Placebo Controlled, Parallel, Multicenter Study of the Effects of 12-weeks of Sodium Zirconium Cyclosilicate (Lokelma) on Albuminuria (UACR) in Patients With Type 2 Diabetes and Hyperkalemia

To investigate whether concomitant treatment with Lokelma can improve the efficacy of standard blockade of the renin-angiotensin system in patients with type 2 diabetes, diabetic nephropathy and hyperkalemia.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus With Kidney Complications
• Intervention / Treatment: Drug: Placebos; Drug: LOKELMA 5 GM Powder for Oral Suspension

Detailed Description

Patients with type 2 diabetes and nephropathy, especially patients with impaired kidney function, frequently encounter hyperkalemia as an adverse effect of RAAS blocking treatment. Consequently, RAAS blocking treatment is reduced or discontinued, which in turn impairs prognosis in terms of long-term renal and cardiovascular outcome. Not only can hyperkalemia as an adverse event lead to changes in RAAS blocking treatment, the presence of persistent potassium levels in the upper part of the normal range can impair the efficacy of the RAAS blocking treatment, another reason to expect a beneficial effect of Lokelma treatment.

The study is a multicentre (3 sites in Sweden (TBD), 2 sites in Denmark (Steno Diabetes Center Copenhagen and Zealand University Hospital, Roskilde), double-blind, randomized placebo-controlled, parallel study. The study drug is compared to matching placebo that cannot be distinguished from active drug. The treatment period is 12 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Peter Rossing, Professor; Phone Number: 0045 30913383; Email: peter.rossing@regionh.dk

Study Locations

• Denmark
  • Gentofte, Denmark, 2820
    • Recruiting
    • Steno Diabetes Center Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female and/or male patients with type 2 diabetes aged 18-85 years
3. Persistent macroalbuminuria (UACR ≥ 200 mg/g in at least two out of the three latest UACR measurements in subject history).
4. Chronic (at least 1 month) stable RAAS blocking treatment, i.e maximum tolerated (individually defined by investigator) dose of an ACE inhibitor or ARB at time of inclusion.
5. Documented hyperkalemia (plasma potassium ≥ 5.0 mmol/l) at least once in the 90 days prior to inclusion in the study.
6. Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
7. Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of Lokelma/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2. Previous enrolment in the present study
3. Use of potassium-lowering agent (loop-diuretics not included)
4. Participation in another clinical study with an investigational product during the last 3 months prior to inclusion.
5. Plasma potassium < 3.5 mmol/l within the previous six months before inclusion.
6. Known hypersensitivity to Lokelma
7. Known history of drug or alcohol abuse within 1 year of screening
8. Estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2 (calculated by CKD-EPI formula).
9. History of long QT syndrome.
10. For women only - currently pregnant (confirmed with positive pregnancy test) or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Lokelma; Sodium zirconium cyclosilicate Lokelma® 5 g, powder (Astra Zeneca) After initial dosing subjects will be instructed to take the study drug once daily in the morning, by oral administration after the powder has been dissolved in a glass of drinking water. Duration: 12 weeks	Drug: LOKELMA 5 GM Powder for Oral Suspension; Sodium zirconium cyclosilicate (a hyperkalemia treatment)
PLACEBO_COMPARATOR: Placebo; Matching placebo (indistinguishable from the active comparator) After initial dosing subjects will be instructed to take the study drug once daily in the morning, by oral administration after the powder has been dissolved in a glass of drinking water. Duration: 12 weeks	Drug: Placebos; Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary albumin creatinine ratio (UACR)	Change in the geometric mean of UACR (milligram per gram) measured in three consecutive morning spot urine collections from baseline to end of treatment	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated glomerular filtration rate (eGFR)	Change in eGFR mL/min/1.73 m2 (CKD-EPI formula) from baseline to end of treatment	12 weeks
Urinary sodium	Change in urinary sodium levels (mmol per liter) in one 24h urine collection from baseline to end of treatment period	12 weeks
Urinary potassium	Change in urinary potassium levels (mmol per liter) in one 24h urine collection from baseline to end of treatment period	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcome - Adverse events	Total number of adverse events from baseline to end of treatment	12 weeks
Safety outcome - Electrocardiogram	Number of adverse events related to changes in the electrocardiogram (e.g. QTc prolongation) from baseline to end of treatment	12 weeks

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Collaborators: Zealand University Hospital; AstraZeneca

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2019
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: August 15, 2019
• First Submitted That Met QC Criteria: August 20, 2019
• First Posted (ACTUAL): August 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 16, 2019
• Last Update Submitted That Met QC Criteria: October 14, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Hyperkalemia; Renin angiotensin system
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Urological Manifestations; Endocrine System Diseases; Urination Disorders; Proteinuria; Water-Electrolyte Imbalance; Diabetes Mellitus; Diabetes Mellitus, Type 2; Albuminuria; Hyperkalemia
• Other Study ID Numbers: 2019-000595-42

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes