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A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03819153
Recruitment Status : Recruiting
First Posted : January 28, 2019
Last Update Posted : April 7, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Tracking Information
First Submitted Date  ICMJE January 18, 2019
First Posted Date  ICMJE January 28, 2019
Last Update Posted Date April 7, 2020
Actual Study Start Date  ICMJE June 17, 2019
Estimated Primary Completion Date August 19, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
Time to first occurrence of a composite primary outcome event defined as persistent eGFR decline of greater than or equal to 50 percentage from trial start, reaching ESRD, death from kidney disease or death from cardiovascular disease [ Time Frame: Week 0 to month 61 ]
Measured in month(s). End Stage Renal Disease (ESRD) is defined as the following individual components: Persistent estimated glomerular filtration rate (eGFR) less than 15 mL/min/1.73m^2 or, Chronic dialysis treatment or receiving a kidney transplantation.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
  • Annual rate of change in eGFR (chronic kidney disease - epidemiology collaboration (CKD-EPI)) (total eGFR slope) [ Time Frame: Week 0 to month 61 ]
    Measured in (mL/min/1.73 m^2)/year.
  • Time to first occurrence of a composite cardiovascular major adverse cardiovascular event (MACE) endpoint consisting of: Non-fatal myocardial infarction, non-fatal stroke, and cardiovascular (CV) death [ Time Frame: Week 0 to month 61 ]
    Measured in month(s).
  • Time to occurrence of all-cause death [ Time Frame: Week 0 to month 61 ]
    Measured in month(s).
  • Time to occurrence of each of the individual components of the primary composite endpoint and of the confirmatory secondary MACE endpoint [ Time Frame: Week 0 to month 61 ]
    Measured in month(s).
  • Time to first occurrence of major adverse limb events (MALE), a composite endpoint consisting of: Acute limb ischemia hospitalisation and chronic limb ischemia hospitalisation [ Time Frame: Week 0 to month 61 ]
    Measured in month(s).
  • Annual rate of change in eGFR (CKD-EPI) (chronic eGFR slope) [ Time Frame: Week 12 to month 61 ]
    Measured in (mL/min/1.73 m^2)/year.
  • Change in eGFR (CKD-EPI) [ Time Frame: Week 0, Week 12 ]
    Measured in mL/min/1.73 m^2.
  • Change in eGFR (cystatin C CKD-EPI) [ Time Frame: Week 0, Year 3 ]
    Measured in mL/min/1.73 m^2.
  • Relative change in urinary albumin-to-creatinine ratio (UACR) [ Time Frame: Week 0, Year 3 ]
    Measured in percentage.
  • Change in body weight [ Time Frame: Week 0, Year 3 ]
    Measured in kilogram.
  • Change in glycosylated haemoglobin (HbA1c) [ Time Frame: Week 0, Year 3 ]
    Measured in percentage point.
  • Change in systolic blood pressure [ Time Frame: Week 0, Year 3 ]
    Measured in mmHg.
  • Change in diastolic blood pressure [ Time Frame: Week 0, Year 3 ]
    Measured in mmHg.
  • Number of severe hypoglycaemic episodes [ Time Frame: Week 0 to month 61 ]
    Number of events.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease
Official Title  ICMJE Effect of Semaglutide Versus Placebo on the Progression of Renal Impairment in Subjects With Type 2 Diabetes and Chronic Kidney Disease
Brief Summary The researchers are doing this study to see if semaglutide can slow down the growth and worsening of chronic kidney disease in people with type 2 diabetes. Participants will get semaglutide (active medicine) or placebo ('dummy medicine'). This is known as participants' study medicine - which treatment participants get is decided by chance. Semaglutide is a medicine, doctors can prescribe in some countries for the treatment of type 2 diabetes. Participants will get the study medicine in a pen. Participants will use the pen to inject the medicine in a skin fold once a week. The study will close when there is enough information collected to show clear result of the study. The total time participants will be in this study is about 3 to 5 years, but it could be longer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Sponsor staff involved in the clinical trial is masked according to company standard procedures
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: Semaglutide
    Participants are to inject semaglutide with a needle in the stomach, thigh or upper arm. Participants will use a pen to inject semaglutide under their skin. Participants will inject semaglutide 1 time a week on the same day of the week. Participants' dose of semaglutide will be changed over time. Participants start by taking a smaller amount (0.25 mg). After 4 weeks the dose will be increased to 0.5 mg. It will be increased more (to 1 mg) at 8 weeks. Participants will then stay on the same dose for the rest of the study.
  • Drug: Placebo (semaglutide)
    Participants are to inject placebo (semaglutide) with a needle in the stomach, thigh or upper arm. Participants will use a pen to inject placebo (semaglutide) under their skin. Participants will inject placebo (semaglutide) 1 time a week on the same day of the week. Participants' dose of placebo (semaglutide) will be changed over time. Participants start by taking a smaller amount (0.25 mg). After 4 weeks the dose will be increased to 0.5 mg. It will be increased more (to 1 mg) at 8 weeks. Participants will then stay on the same dose for the rest of the study.
Study Arms  ICMJE
  • Experimental: Semaglutide
    Participants are to receive semglutide for up to 5 years or more (event driven). The trial is event driven with a pre-defined minimum number of renal endpoint events for the primary endpoint.
    Intervention: Drug: Semaglutide
  • Placebo Comparator: Placebo
    Participants are to receive placebo (semglutide) for up to 5 years or more (event driven). The trial is event driven with a pre-defined minimum number of renal endpoint events for the primary endpoint.
    Intervention: Drug: Placebo (semaglutide)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 7, 2019)
3160
Original Estimated Enrollment  ICMJE
 (submitted: January 25, 2019)
3120
Estimated Study Completion Date  ICMJE August 19, 2024
Estimated Primary Completion Date August 19, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female, age above or equal to 18 years at the time of signing informed consent. Japan: Male or female, age above or equal to 20 years at the time of signing informed consent
  • Diagnosed with type 2 diabetes mellitus
  • HbA1c less than or equal to 10% (less than or equal to 86 mmol/mol)
  • Renal impairment defined either by:

    1. serum creatinine-based eGFR greater than or equal to 50 and less than or equal to 75 mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 300 and less than 5000 mg/g or
    2. serum creatinine-based eGFR greater than or equal to 25 and less than 50 mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 100 and less than 5000 mg/g
  • Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks prior to the date of the laboratory assessments used for determination of the inclusion criteria for renal impairment and kept stable until screening

Exclusion Criteria:

  • Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations
  • Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to screening
  • Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening
  • Presently classified as being in New York Heart Association (NYHA) Class IV heart failure
  • Planned coronary, carotid or peripheral artery revascularisation
  • Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal dialysis
  • Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novo Nordisk (+1) 866-867-7178 clinicaltrials@novonordisk.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   China,   France,   Germany,   Greece,   Hungary,   India,   Israel,   Italy,   Japan,   Malaysia,   Mexico,   Netherlands,   Poland,   Russian Federation,   Slovakia,   South Africa,   Spain,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03819153
Other Study ID Numbers  ICMJE NN9535-4321
U1111-1217-6259 ( Other Identifier: World Health Organization (WHO) )
2018-002878-50 ( Registry Identifier: European Medicines Agency (EudraCT) )
JapicCTI-194843 ( Registry Identifier: JAPIC (Japan) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: https://www.novonordisk-trials.com
Responsible Party Novo Nordisk A/S
Study Sponsor  ICMJE Novo Nordisk A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Reporting Anchor and Disclosure (1452) Novo Nordisk A/S
PRS Account Novo Nordisk A/S
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP