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SGLT2 Inhibitor

Zibotentan + Dapagliflozin for Kidney Disease (ZODIAC Trial)

Phase 2

Waitlist Available

Led By Hiddo J Lambers Heerspink, PhD, PharmD

Research Sponsored by University Medical Center Groningen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥18 and ≤75 years

eGFR ≥ 30 mL/min/1.73m2

Must not have

History of severe hypersensitivity or contraindications to dapagliflozin

Evidence of urinary obstruction or difficulty in voiding at screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 weeks

Summary

This trial tests if combining zibotentan and dapagliflozin can better manage kidney damage in adults with type 2 diabetes. Zibotentan reduces harmful proteins in urine, and dapagliflozin lowers blood sugar and reduces fluid retention. Dapagliflozin is used to treat type 2 diabetes, heart failure, and chronic kidney disease by reducing blood glucose levels.

Who is the study for?

Adults aged 18-75 with type 2 diabetes, HbA1c ≥6.0%, and kidney issues shown by high albumin in urine can join this trial. They must be on stable heart medication for a month and not have type 1 diabetes, severe non-diabetic kidney disease, very high blood sugar, or conditions like heart failure that could risk their safety or affect results.

What is being tested?

The study tests if Zibotentan (a drug blocking certain receptors) combined with Dapagliflozin (a drug reducing sugar absorption in kidneys) better reduces protein leakage into urine than either alone without causing fluid retention. Participants will randomly receive one of the drugs alone, both together, or a placebo.

What are the potential side effects?

Possible side effects include fluid retention leading to swelling (especially with Zibotentan), low blood pressure, dizziness when standing up due to dehydration risks from Dapagliflozin, urinary tract infections, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 75 years old.

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My kidney function is at a safe level for the trial.

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I have been diagnosed with type 2 diabetes.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am severely allergic to dapagliflozin.

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I have trouble urinating or feel blocked.

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I have severe liver problems.

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My heart condition severely limits my daily activities.

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I have not lost or donated more than 400 ml of blood in the last 8 weeks.

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I have been diagnosed with type 1 diabetes.

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My kidney issues causing protein in my urine are not due to diabetes.

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I have been diagnosed with an epilepsy syndrome.

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I am a woman who can still have children and have not been sterilized or reached menopause.

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I have not had any cancer except for skin cancer in the last 5 years.

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I have had major surgery on my stomach or intestines.

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I haven't had stomach ulcers or bleeding in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from baseline in albuminuria after 4 weeks combined zibotentan and dapagliflozin treatment versus four weeks treatment with zibotentan alone.

Secondary study objectives

Body Weight Changes

Change in Extracellular Fluid

Change in Extracellular volume (ECV)

+5 more

Other study objectives

Change in copeptin

Aldosterone

Trial Design

2Treatment groups

Experimental Treatment

Group I: Treatment order 2Experimental Treatment4 Interventions

Subjects will start with 4 weeks of dapagliflozine in treatment period one, then 4 weeks of zibotentan during treatment period two. The order of the first two treatment periods is random which means that patients can start with either dapagliflozine or zibotentan. Then in treatment period three, patients are randomized to either either placebo or dapagliflozin for 2 weeks followed immediately by 4 weeks of both zibotentan and dapagliflozin. Between treatment periods there is a 4-week wash-out.

Group II: Treatment order 1Experimental Treatment4 Interventions

Subjects will start with 4 weeks of placebo in treatment period one, then 4 weeks of zibotentan during treatment period two. The order of the first two treatment periods is random which means that patients can start with either placebo or zibotentan. Then in treatment period three, patients are randomized to either either placebo or dapagliflozin for 2 weeks followed immediately by 4 weeks of both zibotentan and dapagliflozin. Between treatment periods there is a 4-week wash-out.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Zibotentan

2019

Completed Phase 2

~810

Placebo

1995

Completed Phase 3

~2670