Dapagliflozin Treatment in Type 2 Diabetes

NCT04620590 | Completed Phase 4 FDA Drug

• 3 other identifiers: UMCG 20-0012020-001247-12HC6-24-c243179
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 2

Brief Summary

Open label, mechanistic, single-arm study to evaluate the natriuretic effect of 2 weeks dapagliflozin treatment in T2DM patients with impaired renal function. It will measure the average change in 24-hr sodium excretion from average Baseline to average values at Day 2 to 4 within the study group. The study will allow for an up to 6-week Screening and Run-in Period, a 2-week Treatment Period and a 5-day Follow-up Period. Patients will consume food from standardized food boxes starting on Day -6 (patients not on insulin) or Day -20 at the earliest (patients on insulin) of the study until Day 18 (inclusive). Eligible patients will receive dapagliflozin 10 mg tablets once daily for 14±1 days starting on Day 1. This will be followed by a Follow-up Period of 5 days.

Conditions

Diabetes Mellitus, Type 2; Impaired Renal Function

Outcome Measures

Primary Outcomes (1)

• Change in 24-hr sodium excretion

  To investigate change in 24-hr sodium excretion during dapagliflozin treatment between Baseline (average of Days -3 to -1) and average of Days 2 to 4 within each study group in patients with type 2 diabetes mellitus (T2DM) with impaired renal function.

  24 hours

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Patients will receive dapagliflozin 10 mg tablets once daily for 14±1 days.

Drug: Dapagliflozin 10 MG [Farxiga]

Interventions

Dapagliflozin 10 MG [Farxiga] DRUG

Dapagliflozin is a stable, reversible, highly selective, and orally active inhibitor of human renal sodium glucose co-transporter 2 (SGLT2), the major transporter responsible for glucose reabsorption in the kidney. Patients will receive one tablet dapagliflozin 10 mg per day for a total period of 14±1 days. This dose is the recommended dose for monotherapy and for add-on combination therapy with other glucose-lowering medicinal products including insulin to improve glycaemic control in T2DM.

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study-specific procedures.
• Female and/or male aged between 18 years and less than or equal to 80 years.
• A diagnosis of T2DM with HbA1c ≥6.5% (≥48 mmol/mol) and =11% (\<97 mmol/mol); and eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2.
• Patient specific optimal antihypertensive dose of an ACEi or ARB (as per Investigator's judgement) for at least 6 weeks prior to Visit 4 (Day 1).
• A stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to Visit 4 (Day 1) as judged by the Investigator. Metformin, sulphonylurea, DPP4 inhibitors or any combinations of these agents with or without insulin would be accepted but is not mandatory. If used, stable dose of metformin, sulphonylurea, or DPP4 inhibitors or their combination as anti-diabetic therapy for the last 12 weeks prior to start of treatment with dapagliflozin is required.
• Suitable veins for cannulation or repeated venipuncture.
• Female patients 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 study drug 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.
• Patient specific optimal antihypertensive dose of an ACEi or ARB (as per Investigator's judgement) for at least 6 weeks prior to Visit 4 (Day 1).
• A stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to Visit 4 (Day 1) as judged by the Investigator. Metformin, sulphonylurea, DPP4 inhibitors or any combination of these agents with or without insulin would be accepted but is not mandatory. If used, stable dose of metformin, sulphonylurea, or DPP4 inhibitors or their combination as anti-diabetic therapy for the last 12 weeks prior to start of treatment with dapagliflozin is required.

You may not qualify if:

• Previous enrolment in the present study or participation in another clinical study with an investigational product during the last 6 months prior to Screening Visit (Visit 1).
• Involvement in the planning and conduct of the study (applies to both UMCG staff and staff at third party vendor or at investigational sites).
• Hypersensitivity to dapaglifozin, indocyanine green, sodium iodide, or iodine, or patients who have poorly tolerated indocyanine green in the past.
• Pacemaker or other implanted electronic devices.
• Pregnancy.
• Breastfeeding.
• Known clinically significant disease or disorder; or clinically relevant abnormal findings in physical examination, clinical chemistry, haematology and urinalysis; or unstable or rapidly progressing renal disease; other dietary restrictions that would make it difficult for the subject to follow the protocol required diet plan or any other condition or minor medical complaint, which, in the opinion of the investigator, may either put the patient atrisk because of participation in the study, or influence the results, or the patient's ability to participate in the study and comply with study procedures, restrictions and requirements.
• Diagnosis of T1DM.
• Hyperthyroidism or autonomic thyroid adenomas.
• Abnormal vital signs, after 10 minutes supine rest, defined as any opf the following (Visit 1); Systolic blood pressure above 180mmHg; Diastolic blood pressure above 110 mmHg; Pulse less than 50 bpm or greater than 100 bpm.
• Any of the following cardiovascular/vascular within 3 months prior to signing the consent at Visit 1, as assessed by the Investigator: myocardial infarction, cardiac surgery or revascularization (coronary artery bypass graft \[CABG\]/ percutaneous transluminal coronary angioplasty \[PTCA\], unstable angina, unstable heart failure, heart failure New York Association Class IV, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia.
• Patients with severe hepatic impairment (Child-Pugh C).
• Ongoing weight-loss diet (hypocaloric diet) or use of weight-loss agents, unless the diet or treatment has been stopped at least 3 months before Screening Visit, ensuring patients having a stable body weight with no verified body weight variability of greater then 3 kg during the 3 months before Screening Visit.
• Symptoms/complaints suggestive of established neurogenic bladder and/or incomplete bladder emptying.
• History of bladder cancer.

Sponsors & Collaborators

• Emerald Clinical Inc.: lead
• University Medical Center Groningen: collaborator
• Ground Zero Pharmaceuticals: collaborator

Study Sites (2)

CU Anschutz Medical Campus - Clinical Translational Research Center (CTRC)

Aurora, Colorado, 80045, United States

Location

David Cherney, CM, PhD

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Hiddo JL Heerspink

  Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 9, 2020
• Study Start: April 20, 2021
• Primary Completion: May 30, 2023
• Study Completion: November 30, 2023
• Last Updated: April 24, 2025

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (1)