Clinical trial NCT02054897: Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-naïve Subjects With Type 2 Diabetes
Official title: Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-naïve Subjects With Type 2 Diabetes
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: 2014-02-04
Enrollment: 388
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 globally. The aim of this trial is to investigate efficacy and safety of semaglutide once-weekly versus placebo in drug-naïve subjects with type 2 diabetes. (SUSTAIN™ 1-Monotherapy).


Eligibility criteria: Inclusion Criteria: - For Japan only: Male or female, age above or equal to 20 years at the time of signing inform consent - Subjects diagnosed with type 2 diabetes and treated with diet and exercise for at least 30 days before screening - HbA1c 7.0 - 10.0 % (53 - 86 mmol/mol) (both inclusive) Exclusion Criteria: - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice) throughout the trial including the 5 week follow-up period. United Kingdom: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilisation (where partner is sole partner of subject), or true abstinence (when in line with preferred and usual lifestyle) - Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with any glucose lowering agent(s) in a period of 90 days prior to screening. An exception is short-term treatment (no longer than 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value above or equal to 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as eGFR (estimated glomerular filtration rate ) below 30 mL/min/1.73 m\^2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association class IV

Primary outcomes:
measure: Change in HbA1c (Glycosylated Haemoglobin)
timeFrame: Week 0, week 30
Secondary outcomes:
measure: Change in Body Weight
timeFrame: Week 0, week 30
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, week 30
measure: Change in Systolic and Diastolic Blood Pressure
timeFrame: Week 0, week 30
measure: Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target
timeFrame: At 30 weeks of treatment
measure: Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target
timeFrame: At 30 weeks of treatment
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Pell City
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Hawaiian Gardens
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Lomita
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Montclair
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Northridge
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Colorado Springs
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Boynton Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Savannah
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Brownsburg
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Franklin
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Wichita
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Olive Branch
country: United States
facility: Novo Nordisk Investigational Site
state: Mississippi
city: Billings
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Omaha
country: United States
facility: Novo Nordisk Investigational Site
state: Nebraska
city: Belvidere
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: Novo Nordisk Investigational Site
state: New Mexico
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Whiteville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Delaware
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Levittown
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Spartanburg
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sealy
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Vancouver
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Novo Nordisk Investigational Site
state: Manitoba
city: London
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Trois Rivières
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Catania
country: Italy
facility: Novo Nordisk Investigational Site
city: Pisa
country: Italy
facility: Novo Nordisk Investigational Site
city: Roma
country: Italy
facility: Novo Nordisk Investigational Site
city: Rome
country: Italy
facility: Novo Nordisk Investigational Site
city: Siena
country: Italy
facility: Novo Nordisk Investigational Site
city: Terni
country: Italy
facility: Novo Nordisk Investigational Site
city: Kyoto-shi, Kyoto
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: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Monterrey
country: Mexico
facility: Novo Nordisk Investigational Site
state: Nuevo León
city: Ciudad Madero
country: Mexico
facility: Novo Nordisk Investigational Site
state: Tamaulipas
city: Aguascalientes
country: Mexico
facility: Novo Nordisk Investigational Site
city: Oradea
country: Romania
facility: Novo Nordisk Investigational Site
state: Bihor
city: Bucharest
country: Romania
facility: Novo Nordisk Investigational Site
city: Bucharest
country: Romania
facility: Novo Nordisk Investigational Site
city: Buzau
country: Romania
facility: Novo Nordisk Investigational Site
city: Galati
country: Romania
facility: Novo Nordisk Investigational Site
city: Arkhangelsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Arkhangelsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kazan
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-Petesburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Stavropol
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Port Elizabeth
country: South Africa
facility: Novo Nordisk Investigational Site
state: Eastern Cape
city: Bloemfontein
country: South Africa
facility: Novo Nordisk Investigational Site
state: Free State
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Krugersdorp
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Sophiatown
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Umkomaas
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Cardiff
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Dundee
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: St Helens
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Swansea
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Overgaard RV, Lindberg SO, Thielke D. Impact on HbA1c and body weight of switching from other GLP-1 receptor agonists to semaglutide: A model-based approach. Diabetes Obes Metab. 2019 Jan;21(1):43-51. doi: 10.1111/dom.13479. Epub 2018 Aug 23.
citation: Fonseca VA, Capehorn MS, Garg SK, Jodar Gimeno E, Hansen OH, Holst AG, Nayak G, Seufert J. Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. J Clin Endocrinol Metab. 2019 Sep 1;104(9):4078-4086. doi: 10.1210/jc.2018-02685.
citation: Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA1C >/=1.0% AND WEIGHT >/=5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13.
citation: Sorli C, Harashima SI, Tsoukas GM, Unger J, Karsbol JD, Hansen T, Bain SC. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017 Apr;5(4):251-260. doi: 10.1016/S2213-8587(17)30013-X. Epub 2017 Jan 17.
citation: Warren M, Chaykin L, Trachtenbarg D, Nayak G, Wijayasinghe N, Cariou B. Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2291-2297. doi: 10.1111/dom.13331. Epub 2018 Jun 7.
citation: Petri KCC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes. Diabetes Obes Metab. 2018 Sep;20(9):2238-2245. doi: 10.1111/dom.13358. Epub 2018 Jun 15.
citation: Ahren B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S, Holst AG, Leiter LA. Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12.
citation: DeVries JH, Desouza C, Bellary S, Unger J, Hansen OKH, Zacho J, Woo V. Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. Diabetes Obes Metab. 2018 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9.
citation: Carlsson Petri KC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Semaglutide s.c. Once-Weekly in Type 2 Diabetes: A Population Pharmacokinetic Analysis. Diabetes Ther. 2018 Aug;9(4):1533-1547. doi: 10.1007/s13300-018-0458-5. Epub 2018 Jun 15.
citation: Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jodar E, Mehta R, Woo V, Lingvay I. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4.
citation: Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.
citation: Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.
citation: DeSouza C, Cariou B, Garg S, Lausvig N, Navarria A, Fonseca V. Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials. J Clin Endocrinol Metab. 2020 Feb 1;105(2):dgz072. doi: 10.1210/clinem/dgz072.