Clinical trial NCT03086330: Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus
Official title: Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus. A 30-week Randomised, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-03-22
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Asia, Europe and North America. The aim of the trial is to compare the effect of semaglutide s.c. 1.0 mg once-weekly versus placebo as add-on to sodium glucose co-transporter-2 inhibitor (SGLT-2i) monotherapy or in combination with either metformin or sulfonylurea on glycaemic control after 30 weeks of treatment in subjects with type 2 diabetes. Subjects will remain on their pre-trial medication.


Eligibility criteria: Inclusion Criteria:

* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
* Male or female, above or equal to 18 years at the time of signing informed consent. For Japan only: Male or female, age equal to or above 20 years at the time of signing informed consent
* Diagnosed with type 2 diabetes mellitus
* HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive)
* Stable dose of an SGLT-2 inhibitor as monotherapy or in combination (including fixed-dose drug combination) with a stable dose of metformin (equal to or above 1500 mg or maximum tolerated dose) or a SU for at least 90 days prior to the day of screening. All medications in compliance with current local label

Exclusion Criteria:

* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice)
* Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
* Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed
* Subjects with alanine aminotransferase above 2.5 x upper normal limit
* Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative
* History or presence of pancreatitis (acute or chronic)
* History of diabetic ketoacidosis
* Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening
* Subjects presently classified as being in New York Heart Association Class IV
* Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
* Renal impairment measured as estimated Glomerular Filtration Rate value of eGFR below 60 ml/min/1.73 m\^2 as defined by KDIGO 2012 classification using isotope dilution mass spectrometry for serum creatinine measured at screening
* Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within the past 90 days prior to randomisation
* Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed

Primary outcomes:
measure: Change in HbA1c
timeFrame: Week 0, week 30
Secondary outcomes:
measure: Change in Body Weight (kg)
timeFrame: Week 0, week 30
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, week 30
measure: Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean 7-point Profile
timeFrame: Week 0, week 30
measure: Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean Post Prandial Increment (Over All Meals)
timeFrame: Week 0, week 30
measure: Change in Fasting Blood Lipid, Total Cholesterol
timeFrame: Week 0, week 30
measure: Change in Fasting Blood Lipid, Low-density Lipoprotein (LDL) Cholesterol
timeFrame: Week 0, week 30
measure: Change in Fasting Blood Lipid, High-density Lipoprotein (HDL) Cholesterol
timeFrame: Week 0, week 30
measure: Change in Fasting Blood Lipid, Triglycerides
timeFrame: Week 0, week 30
measure: Change in Body Weight (%)
timeFrame: Week 0, week 30
measure: Change in Body Mass Index
timeFrame: Week 0, week 30
measure: Change in Waist Circumference
timeFrame: Week 0, week 30
measure: Change in Systolic Blood Pressure
timeFrame: Week 0, week 30
measure: Change in Diastolic Blood Pressure
timeFrame: Week 0, week 30
measure: Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains
timeFrame: Week 0, week 30
measure: Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately
timeFrame: Week 0, week 30
measure: HbA1c Below 7.0% (53 mmol/Mol)
timeFrame: After 30 weeks
measure: HbA1c Equal to or Below 6.5% (48 mmol/Mol)
timeFrame: After 30 weeks
measure: Weight Loss Equal to or Above 3%
timeFrame: After 30 weeks
measure: Weight Loss Equal to or Above 5%
timeFrame: After 30 weeks
measure: Weight Loss Equal to or Above 10%
timeFrame: After 30 weeks
measure: HbA1c Below 7.0% (53 mmol/Mol) Without Severe or BG Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain
timeFrame: After 30 weeks
measure: HbA1c Reduction Equal to or Above 1%-Point
timeFrame: After 30 weeks
measure: HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 3%
timeFrame: After 30 weeks
measure: HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 5%
timeFrame: After 30 weeks
measure: HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 10%
timeFrame: After 30 weeks
measure: Number of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Week 0 - week 30
measure: Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Week 0 - week 30
measure: Change in Haematology: Haemoglobin
timeFrame: Week 0, week 30
measure: Change in Haematology: Haematocrit
timeFrame: Week 0, week 30
measure: Change in Haematology: Thrombocytes
timeFrame: Week 0, week 30
measure: Change in Haematology: Erythrocytes
timeFrame: Week 0, week 30
measure: Change in Haematology: Leucocytes
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Amylase
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Lipase
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Alkaline Phosphatase
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Alanine Aminotransferase
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Aspartate Aminotransferase
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Total Bilirubin
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Albumin
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Calcium (Total)
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Potassium
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Sodium
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Bicarbonate
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Week 0, week 30
measure: Change in Biochemistry: Creatinine
timeFrame: Week 0, week 30
measure: Change in Calcitonin
timeFrame: Week 0, week 30
measure: Change in Pulse
timeFrame: Week 0, week 30
measure: Change in Electrocardiogram
timeFrame: Week 0, week 30
measure: Change in Physical Examination: General Appearance
timeFrame: Week -2, week 30
measure: Change in Physical Examination: Central and Peripheral Nervous System
timeFrame: Week -2, week 30
measure: Change in Physical Examination: Cardiovascular System
timeFrame: Week -2, week 30
measure: Change in Physical Examination: Gastrointestinal System Including Mouth
timeFrame: Week -2, week 30
measure: Change in Physical Examination: Skin
timeFrame: Week -2, week 30
measure: Change in Physical Examination: Respiratory System
timeFrame: Week -2, week 30
measure: Change in Physical Examination: Lymph Node Palpation
timeFrame: Week -2, week 30
measure: Change in Physical Examination: Thyroid Gland
timeFrame: Week -2, week 30
measure: Change in Fundoscopy
timeFrame: Week 0, week 30
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Anniston
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Glendale
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Tempe
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Novo Nordisk Investigational Site
state: Arkansas
city: La Jolla
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Lincoln
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Northridge
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Edgewater
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Maitland
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Lawrenceville
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Woodstock
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Hutchinson
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Troy
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Jefferson City
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Albany
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Smithtown
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: West Seneca
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Gastonia
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Kinston
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Morehead City
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Norman
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Beaver
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: McMurray
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Arlington
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Irving
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Shavano Park
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Victoria
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Murray
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Chesapeake
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Olympia
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Saint Stefan
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Edmonton
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Winnipeg
country: Canada
facility: Novo Nordisk Investigational Site
state: Manitoba
city: Brampton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Brampton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Etobicoke
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Smiths Falls
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Waterloo
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Nagakute-shi, Aichi
country: Japan
facility: Novo Nordisk Investigational Site
city: Suita-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Hamar
country: Norway
facility: Novo Nordisk Investigational Site
city: Hoenefoss
country: Norway
facility: Novo Nordisk Investigational Site
city: Namsos
country: Norway
facility: Novo Nordisk Investigational Site
city: Olso
country: Norway
facility: Novo Nordisk Investigational Site
city: Oslo
country: Norway
facility: Novo Nordisk Investigational Site
city: Skedsmokorset
country: Norway
facility: Novo Nordisk Investigational Site
city: Stavanger
country: Norway
facility: Novo Nordisk Investigational Site
city: Ponce
country: Puerto Rico
facility: Novo Nordisk Investigational Site
city: Barnaul
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Zinman B, Bhosekar V, Busch R, Holst I, Ludvik B, Thielke D, Thrasher J, Woo V, Philis-Tsimikas A. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019 May;7(5):356-367. doi: 10.1016/S2213-8587(19)30066-X. Epub 2019 Mar 1.