Dose-Response Effect, Efficacy, and Safety of AZD5718 in Reducing Albuminuria in Participants with Proteinuric Chronic Kidney Disease
- Conditions
- Proteinuric Chronic Kidney DiseaseMedDRA version: 23.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Symptoms and general pathology [C23]
- Registration Number
- EUCTR2020-002263-54-PL
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 632
1. Male or female, aged at least 18 years.
2. Participants with proteinuric CKD defined as:
- eGFR 20 – 75 mL/min/1.73m2
- albuminuria defined as 200 -5000 mg albumin/g creatinine
- diagnosis of T2DM (for DKD sub-group only)
3. Body weight within 50-150 kg and BMI within the range 18 to 45 kg/m2 (inclusive).
4. Female participants must be of non-childbearing potential and must have been be surgically sterilized or be postmenopausal. All female participants must have a negative serum pregnancy test.
5. Male participants must be surgically sterile or agree to use highly effective contraceptives. Non sterilised male participants who are sexually active with a female partner of childbearing potential must use a male condom with spermicide.
6. Blood Pressure = 150/100 mmHg and a stable dose of ACEi or ARB and other antihypertensive therapy including diuretic for at least 4 weeks prior to Visit 1.
7. For participants on any additional antihypertensive medication (including diuretic therapy), the doses must be stable for at least 4 weeks prior to Visit 1.
8. The participants must have been on a stable dose for at least 4 weeks prior to randomisation visit:
- if on SGLT2i or GLP1-RA treatment; no new additional SGLT2i or GLP1-RA therapy is permitted until the 8-week extension period.
- if on treatment with other drugs with potential to influence albuminuria, eg NSAIDs
- the renin inhibitor or an aldosterone antagonist in combination with an ACEi or an ARB (dual renin angiotensin aldosterone system inhibitor therapy) is permitted
9. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional exploratory genetic research that supports Genomic Initiative
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 379
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 253
1. Recent hepatitis, or positive screening test for hepatitis B (hepatitis B virus surface antigen) or hepatitis C (hepatitis C antibody).
2. Diagnosis of:
- polycystic kidney disease or anatomical causes of CKD
- T1DM
3. Participants with severe hepatic impairment (Child-Pugh class C).
4. Abnormal laboratory findings at Screening Visit 1:
- Alanine aminotransferase or AST > 2 × ULN or total bilirubin > 2 × ULN (unless due to Gilbert’s disease) or evidence of chronic liver disease.
- Serum potassium > 5.5 mmol/L that cannot be adjusted to values = 5.5 mmol/L by appropriate management.
5. Any of the following concomitant conditions or diseases at Screening Visit 1:
- History of QT prolongation associated with other medications that required discontinuation of that medication
- Congenital long QT syndrome
- Acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass grafting within 6 months
- High degree atrioventricular block II-III, sinus node dysfunction with significant sinus pause, untreated with pacemaker
- Stroke within 3 months
- Heart failure New York Heart Association classification III-IV
- Anticipated dialysis or renal transplantation within 1 year
- History of substance dependence or a positive screen for drugs or alcohol abuse
- Prior malignancy other than non-melanoma skin cancer or cervical cancer in situ treated with apparent success with curative therapy (response duration of > 5 years).
- Any other condition or clinically relevant abnormal findings in physical examination, laboratory results or ECG during screening period
6. Participant who had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks of Screening Visit 1.
7. Ongoing use of any biologic drug and/or small molecule targeting the immune system
8. Any serum creatinine-altering drugs within 1 month prior to Screening Visit 1
9. Any concomitant medications known to be associated with Torsades de Pointes or potent inducers/inhibitors of cytochrome P450 3A4.
10. Treatment with:
- zileuton, cilastatin (DPEP1 inhibitor), or leukotriene receptor antagonists within 4 weeks of Screening Visit 1.
- simvastatin, lovastatin, and atorvastatin at doses > 40 mg per day within 1 month prior to Screening Visit 1.
11. Donation of blood or significant blood loss in excess of 500 mL within 3 months prior to Day 1 (or > 1200 mL in the year prior to Day 1).
12. Plasma donation within 60 days prior to Day 1.
13. Female currently pregnant or breast-feeding.
14. Participants who are legally institutionalized.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method