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

Primary Purpose

Type 2 Diabetes Mellitus With Kidney Complications

Status

Unknown status

Phase

Phase 4

Locations

Denmark

Study Type

Interventional

Intervention

LOKELMA 5 GM Powder for Oral Suspension

Placebos

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus With Kidney Complications focused on measuring Hyperkalemia, Renin angiotensin system

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Provision of informed consent prior to any study specific procedures
Female and/or male patients with type 2 diabetes aged 18-85 years
Persistent macroalbuminuria (UACR ≥ 200 mg/g in at least two out of the three latest UACR measurements in subject history).
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.
Documented hyperkalemia (plasma potassium ≥ 5.0 mmol/l) at least once in the 90 days prior to inclusion in the study.
Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
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:

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

Sites / Locations

Steno Diabetes Center CopenhagenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Lokelma

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Estimated glomerular filtration rate (eGFR)

Change in eGFR mL/min/1.73 m2 (CKD-EPI formula) from baseline to end of treatment

Urinary sodium

Change in urinary sodium levels (mmol per liter) in one 24h urine collection from baseline to end of treatment period

Urinary potassium

Change in urinary potassium levels (mmol per liter) in one 24h urine collection from baseline to end of treatment period

Full Information

NCT ID

NCT04063930

First Posted

August 15, 2019

Last Updated

October 14, 2019

Sponsor

Steno Diabetes Center Copenhagen

Collaborators

AstraZeneca, Zealand University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04063930

Brief Title

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

Acronym

ZIRCUS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Unknown status

Study Start Date

October 2019 (Anticipated)

Primary Completion Date

December 2020 (Anticipated)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Steno Diabetes Center Copenhagen

Collaborators

AstraZeneca, Zealand University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus With Kidney Complications

Keywords

Hyperkalemia, Renin angiotensin system

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Lokelma

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

LOKELMA 5 GM Powder for Oral Suspension

Intervention Description

Sodium zirconium cyclosilicate (a hyperkalemia treatment)

Intervention Type

Drug

Intervention Name(s)

Placebos

Intervention Description

Matching placebo

Primary Outcome Measure Information:

Title

Urinary albumin creatinine ratio (UACR)

Description

Change in the geometric mean of UACR (milligram per gram) measured in three consecutive morning spot urine collections from baseline to end of treatment

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Estimated glomerular filtration rate (eGFR)

Description

Change in eGFR mL/min/1.73 m2 (CKD-EPI formula) from baseline to end of treatment

Time Frame

12 weeks

Title

Urinary sodium

Description

Change in urinary sodium levels (mmol per liter) in one 24h urine collection from baseline to end of treatment period

Time Frame

12 weeks

Title

Urinary potassium

Description

Change in urinary potassium levels (mmol per liter) in one 24h urine collection from baseline to end of treatment period

Time Frame

12 weeks

Other Pre-specified Outcome Measures:

Title

Safety outcome - Adverse events

Description

Total number of adverse events from baseline to end of treatment

Time Frame

12 weeks

Title

Safety outcome - Electrocardiogram

Description

Number of adverse events related to changes in the electrocardiogram (e.g. QTc prolongation) from baseline to end of treatment

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Provision of informed consent prior to any study specific procedures Female and/or male patients with type 2 diabetes aged 18-85 years Persistent macroalbuminuria (UACR ≥ 200 mg/g in at least two out of the three latest UACR measurements in subject history). 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. Documented hyperkalemia (plasma potassium ≥ 5.0 mmol/l) at least once in the 90 days prior to inclusion in the study. Negative pregnancy test (urine or serum) for female subjects of childbearing potential. 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: Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) Previous enrolment in the present study Use of potassium-lowering agent (loop-diuretics not included) Participation in another clinical study with an investigational product during the last 3 months prior to inclusion. Plasma potassium < 3.5 mmol/l within the previous six months before inclusion. Known hypersensitivity to Lokelma Known history of drug or alcohol abuse within 1 year of screening Estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2 (calculated by CKD-EPI formula). History of long QT syndrome. For women only - currently pregnant (confirmed with positive pregnancy test) or breast feeding.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Peter Rossing, Professor

Phone

0045 30913383

peter.rossing@regionh.dk

Facility Information:

Facility Name

Steno Diabetes Center Copenhagen

City

Gentofte

ZIP/Postal Code

2820

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Peter Rossing, MD

peter.rossing@regionh.dk

First Name & Middle Initial & Last Name & Degree

Peter Rossing, MD

12. IPD Sharing Statement

Plan to Share IPD

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

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