We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03819153
Recruitment Status : Active, not recruiting
First Posted : January 28, 2019
Last Update Posted : May 17, 2023
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Semaglutide Drug: Placebo (semaglutide) Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3508 participants
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
Official Title: Effect of Semaglutide Versus Placebo on the Progression of Renal Impairment in Subjects With Type 2 Diabetes and Chronic Kidney Disease
Actual Study Start Date : June 17, 2019
Estimated Primary Completion Date : August 19, 2024
Estimated Study Completion Date : August 19, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
Drug Information available for: Semaglutide

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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.
 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.
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.
 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. Time to occurrence of all-cause death [ Time Frame: Week 0 to month 61 ]
    Measured in month(s).

  4. 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).

  5. 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).

  6. 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.

  7. Change in eGFR (CKD-EPI) [ Time Frame: Week 0, Week 12 ]
    Measured in mL/min/1.73 m^2.

  8. Change in eGFR (cystatin C CKD-EPI) [ Time Frame: Week 0, Year 3 ]
    Measured in mL/min/1.73 m^2.

  9. Relative change in urinary albumin-to-creatinine ratio (UACR) [ Time Frame: Week 0, Year 3 ]
    Measured in percentage.

  10. Change in body weight [ Time Frame: Week 0, Year 3 ]
    Measured in kilogram.

  11. Change in glycosylated haemoglobin (HbA1c) [ Time Frame: Week 0, Year 3 ]
    Measured in percentage point.

  12. Change in systolic blood pressure [ Time Frame: Week 0, Year 3 ]
    Measured in mmHg.

  13. Change in diastolic blood pressure [ Time Frame: Week 0, Year 3 ]
    Measured in mmHg.

  14. Number of severe hypoglycaemic episodes [ Time Frame: Week 0 to month 61 ]
    Number of events.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03819153


Locations
Show Show 394 study locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Layout table for investigator information
Study Director: Clinical Transparency (dept. 1452) Novo Nordisk A/S
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03819153    
Other Study ID Numbers: 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) )
First Posted: January 28, 2019    Key Record Dates
Last Update Posted: May 17, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: https://www.novonordisk-trials.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Renal Insufficiency, Chronic
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
 Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Renal Insufficiency
Chronic Disease
Disease Attributes
Pathologic Processes