- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04492722
A Study to Evaluate the Safety and Efficacy of AZD5718 in Participants With Proteinuric Chronic Kidney Disease
A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Multi-Centre, Dose-Ranging Study of AZD5718 in Participants With Proteinuric Chronic Kidney Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Bahia Blanca, Argentina, B8109
- Research Site
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Buenos Aires, Argentina, 1280
- Research Site
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Cordoba, Argentina, 5000
- Research Site
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Cordoba, Argentina, X5016KEH
- Research Site
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Cordoba, Argentina, X5016KET
- Research Site
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Junín, Argentina, 6000
- Research Site
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Mar del Plata, Argentina, B7600
- Research Site
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Belem, Brazil, 66073-005
- Research Site
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Brasilia, Brazil, 71625-175
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Curitiba, Brazil, 80215-901
- Research Site
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Fortaleza, Brazil, 60430-375
- Research Site
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Meireles, Brazil, 60160-230
- Research Site
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Porto Alegre, Brazil, 90035-074
- Research Site
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Porto Alegre, Brazil, 90430-001
- Research Site
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Santo Andre, Brazil, 09090-790
- Research Site
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Sao Paulo, Brazil, 05403-9000
- Research Site
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São Paulo, Brazil, 01323-020
- Research Site
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São Paulo, Brazil, 05016-090
- Research Site
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Aschaffenburg, Germany, 63739
- Research Site
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Berlin, Germany, 13509
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Essen, Germany, 45136
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Trier, Germany, 54292
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Balatonfüred, Hungary, 8230
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Budapest, Hungary, 1083
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Budapest, Hungary, 1115
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Debrecen, Hungary, 4032
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Szentes, Hungary, 6600
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Szigetvár, Hungary, 7900
- Research Site
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Afula, Israel, 1834111
- Research Site
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Ashdod, Israel, 7747629
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Ashkelon, Israel, 78306
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Haifa, Israel, 34362
- Research Site
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Jerusalem, Israel, 91031
- Research Site
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Ageo, Japan, 362-8588
- Research Site
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Asahikawa-shi, Japan, 070-8530
- Research Site
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Chiba-shi, Japan, 261-0004
- Research Site
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Hiroshima, Japan, 732-0057
- Research Site
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Kasugai-shi, Japan, 486-8510
- Research Site
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Kitakyushu, Japan, 805-8508
- Research Site
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Koga-shi, Japan, 306-0041
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Kyoto-shi, Japan, 604-8845
- Research Site
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Mito-shi, Japan, 311-4198
- Research Site
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Morioka-shi, Japan, 020-0066
- Research Site
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Osaka, Japan, 553-0003
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Osaka-shi, Japan, 558-8558
- Research Site
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Osaka-shi, Japan, 530-0005
- Research Site
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Sashima-gun, Japan, 306-0433
- Research Site
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Shizuoka-shi, Japan, 420-8630
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Toride-shi, Japan, 302-0022
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Yokohama-shi, Japan, 236-0004
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Yokohama-shi, Japan, 234-0054
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Yokohama-shi, Japan, 247-8581
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Kota Kinabalu, Malaysia, 88586
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Kuala Lumpur, Malaysia, 59100
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Kuala Lumpur, Malaysia, 50586
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Kuala Lumpur, Malaysia, 56000
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Malacca, Malaysia, 78300
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Seremban, Malaysia, 70300
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Seri Manjung, Malaysia, 32040
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Sibu, Malaysia, 96000
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Bialystok, Poland, 15-375
- Research Site
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Białystok, Poland, 15-435
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Kraków, Poland, 31-559
- Research Site
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Oswiecim, Poland, 32-600
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Rzeszow, Poland, 35-055
- Research Site
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Łódź, Poland, 92-213
- Research Site
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Kaohsiung, Taiwan, 833
- Research Site
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Kaohsiung City, Taiwan, 82445
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Keelung, Taiwan, 20448
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New Taipei City, Taiwan, 23148
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Taichung, Taiwan, 40705
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Taichung, Taiwan, 40443
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Taichung, Taiwan, 433
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Taipei, Taiwan, 100
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Taipei, Taiwan, 116
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Taipei 112, Taiwan
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Dnipro, Ukraine, 49005
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Dnipro, Ukraine, 49038
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Ivano-Frankivsk, Ukraine, 76014
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Ivano-Frankivsk, Ukraine, 76000
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Kyiv, Ukraine, 02125
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Kyiv, Ukraine, 03049
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Kyiv, Ukraine, 1004
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Lviv, Ukraine, 79010
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Uzhhorod, Ukraine, 88018
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Vinnytsia, Ukraine, 21001
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Vinnytsia, Ukraine, 21010
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Zaporizhzhia, Ukraine, 69600
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Zhytomyr, Ukraine, 10002
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California
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Canoga Park, California, United States, 91303
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La Mesa, California, United States, 91942
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San Carlos, California, United States, 94070
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San Francisco, California, United States, 94110
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Victorville, California, United States, 92392
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Colorado
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Denver, Colorado, United States, 80045
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Florida
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Jacksonville, Florida, United States, 32216
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Winter Haven, Florida, United States, 33880
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Georgia
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Columbus, Georgia, United States, 31904
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Michigan
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Roseville, Michigan, United States, 48066
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Missouri
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Hazelwood, Missouri, United States, 63042
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New York
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Fresh Meadows, New York, United States, 11365
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Great Neck, New York, United States, 11021
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Jamaica, New York, United States, 11432
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Ohio
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Blue Ash, Ohio, United States, 45242
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Rhode Island
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East Providence, Rhode Island, United States, 02914
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Tennessee
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Memphis, Tennessee, United States, 38104-2127
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Texas
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Austin, Texas, United States, 78738
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Houston, Texas, United States, 77099
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Pearland, Texas, United States, 77584
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San Antonio, Texas, United States, 78215
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Schertz, Texas, United States, 78154
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Capable of giving signed informed consent form.
- Male or female adults, >= 18 years of age at study entry.
- For participants who haven't reached the age of maturity according to local regulations in their country, a written informed consent should be obtained from the participant and participants legally acceptable representative.
- Body weight within 50-150 kg and body mass index within the range 18 to 45 kg/m^2.
Participants with proteinuric CKD defined as:
- eGFR 20 - 75 mL/min/1.73m^2 based on Chronic Kidney Disease Epidemiology Collaboration equation at Screening Visit 1.
- Albuminuria defined as 200 -5000 mg albumin/g creatinine based on the geometric mean of the replicated measurements using 3 sequential first morning void urine at Visit 2.
- Participants with diagnosis of Type 2 Diabetes Mellitus (DM) [for DKD sub-group only].
- Females of non-childbearing potential must have been surgically sterilized or be postmenopausal, and all female participants must have a negative pregnancy test at screening and prior to study drug administration.
- Male participants must be surgically sterile or agree to use highly effective contraceptives. Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from Day 1 to 3 months after the last dose of the study drug. Approved/Certified measurements in Japan are as Vasectomy, tubal occlusion, intrauterine device (provided coils are copper banded), levonorgestrel intrauterine system (eg, Mirena®). These measurements are acceptable forms of highly effective birth control in Japan. Not Approved/Certified measurements in Japan are as: Cerazette® (desogestrel) pills, medroxyprogesterone injections (eg, Depo-Provera®), etonogestrel implants (eg, Implanon®, Norplan®), normal and low dose combined oral pills, norelgestromin/ethinylestradiol transdermal system (eg, Evra® Patch), intravaginal device (eg, NuvaRing®).
- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional exploratory genetic research.
- Participants should have: a) stable blood pressure (BP [BP <= 150/100 mmHg at Visit 1, and 3]); b)stable dose of angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) for at least 4 weeks prior to Screening Visit 1; c) participants who have been unable to tolerate ACEi or ARB therapy may be enrolled.
- Participants must have been on a stable dose for at least 4 weeks prior to Screening Visit 1, who have been on additional antihypertensives (including diuretics); on treatment with drugs with potential to influence albuminuria eg., non-steroidal anti-inflammatory drug; on renin inhibitor or an aldosterone antagonist in combination with an ACEi or an ARB.
- Participants on Sodium-glucose co-transporter-2 inhibitors (SGLT2i) or Glucagon-like peptide-1 receptor agonist (GLP1-RA) treatment, the participants must have been on a stable dose for at least 4 weeks prior to randomization visit.
Exclusion Criteria:
- Participants with recent positive hepatitis B or hepatitis C.
- Diagnosis of polycystic kidney disease or anatomical causes of CKD.
- Diagnosis of Type 1 DM.
- Participants with severe hepatic impairment (Child-Pugh class C).
- Abnormal laboratory findings at Screening Visit 1.
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, and 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.
- Stroke within 3 months, heart failure, and anticipated dialysis or renal transplantation within 1 year.
- Any other condition or clinically relevant abnormal findings in physical examination, laboratory results or ECG during screening period.
- History of substance dependence or a positive screen for drugs or alcohol abuse. Alcohol and drug screening to be completed for all participants locally with laboratory kits provided by the central laboratory.
- 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.
- Ongoing use of any biologic drug and/or small molecule targeting the immune system.
- Any serum creatinine-altering drugs within 1 month prior to Screening Visit 1.
- Treatment with any concomitant medications known to be associated with Torsades de Pointes or potent inducers/inhibitors of cytochrome P450 3A4 within 4 weeks of Visit 3 (Randomization).
- Treatment with zileuton, cilastatin (dipeptidase-1 [DPEP1] inhibitor), or leukotriene receptor antagonists (eg, montelukast) within 4 weeks of Screening Visit 1.
- Treatment with simvastatin, lovastatin, and atorvastatin at doses > 40 mg per day within 1 month prior to Screening Visit 1.
- Concurrent enrollment in another clinical study involving an investigational treatment or drug or participation in a device study within 3 months prior to Screening Visit 1.
- Participants with a known hypersensitivity to AZD5718 or any of the excipients of the product. Participants with a known hypersensitivity to dapagliflozin or any of the excipients of the product.
- 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).
- Plasma donation within 60 days prior to Day 1.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study center).
- Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
- For women only - currently pregnant (a negative serum pregnancy test is required at Screening Visit 1 and urine pregnancy test at Day 1 [Visit 3]) or breast-feeding.
- An employee, or close relative of an employee, of AstraZeneca, the Contract Research Organisation, or the study site, regardless of the employee's role.
- Participants who are legally institutionalized.
- Participants working night shifts, and who cannot avoid strenuous manual labour during the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: AZD5718 Dose 1 + Dapagliflozin 10 mg
Participants will receive once daily oral dose 1 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
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Participants will receive once daily oral dose of AZD5718 as per the arms they are randomised, and will continue until Week 20.
Participants will receive once daily oral dose of 10 mg dapagliflozin for 8 weeks as an add-on therapy.
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Experimental: AZD5718 Dose 2 + Dapagliflozin 10 mg
Participants will receive once daily oral dose 2 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
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Participants will receive once daily oral dose of AZD5718 as per the arms they are randomised, and will continue until Week 20.
Participants will receive once daily oral dose of 10 mg dapagliflozin for 8 weeks as an add-on therapy.
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Experimental: AZD5718 Dose 3 + Dapagliflozin 10 mg
Participants will receive once daily oral dose 3 of AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
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Participants will receive once daily oral dose of AZD5718 as per the arms they are randomised, and will continue until Week 20.
Participants will receive once daily oral dose of 10 mg dapagliflozin for 8 weeks as an add-on therapy.
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Placebo Comparator: Placebo + Dapagliflozin 10 mg
Participants will receive once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
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Participants will receive once daily oral dose of 10 mg dapagliflozin for 8 weeks as an add-on therapy.
Participants will receive once daily oral dose of placebo matched to AZD5718, and will continue until Week 20.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Reduction of Urine Albumin to Creatinine Ratio (ACR) to Week 20
Time Frame: Week 1 (Baseline) to Week 20
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The dose response effect of AZD5718 on urine ACR at 20 weeks was evaluated.
Values less than 1 indicate improvement from baseline.
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Week 1 (Baseline) to Week 20
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Reduction of Urine ACR to Week 12
Time Frame: Week 1 (Baseline) to Week 12
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The dose response effect of AZD5718 on urine ACR at 12 weeks was evaluated.
Values less than 1 indicate improvement from baseline.
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Week 1 (Baseline) to Week 12
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Number of Participants With Adverse Events and Serious Adverse Events
Time Frame: From Screening (Week -4 to 0) to Week 24
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The safety and tolerability profile of AZD5718 treatment was assessed
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From Screening (Week -4 to 0) to Week 24
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Change From Baseline in 24-hours Mean Systolic Blood Pressure to Week 12
Time Frame: Week 1 (Baseline) to Week 12
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The effect of AZD5718 on ambulatory blood pressure was assessed
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Week 1 (Baseline) to Week 12
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Plasma Concentrations of AZD5718
Time Frame: From Week 2 to Week 20
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The PK of AZD5718 after repeated oral dosing for 20 weeks was evaluated
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From Week 2 to Week 20
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Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) to Week 12
Time Frame: Week 1 (Baseline), Week 2, Week 4, Week 8, and Week 12
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The effect of AZD5718 on renal function was evaluated
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Week 1 (Baseline), Week 2, Week 4, Week 8, and Week 12
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hiddo J. L. Heerspink, Department of Clinical Pharmacy and Pharmacology University Medical Centre Groningen
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Urologic Diseases
- Disease Attributes
- Renal Insufficiency
- Chronic Disease
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Kidney Diseases
- Renal Insufficiency, Chronic
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Sodium-Glucose Transporter 2 Inhibitors
- Dapagliflozin
Other Study ID Numbers
- D7551C00001
- 2020-002263-54 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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