A Trial Comparing the Safety and Efficacy of Semaglutide Once Weekly in Monotherapy or in Combination With One OAD in Japanese Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— SUSTAIN™  

Official title:

Safety and Efficacy of Semaglutide Once Weekly in Monotherapy or in Combination With One OAD in Japanese Subjects With Type 2 Diabetes Who Are Insufficiently Controlled on Diet/Exercise Therapy or OAD Monotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02207374
• Other study ID #: NN9535-4091
• Secondary ID: U1111-1140-3081J
• Status: Completed
• Phase: Phase 3
• Start date: August 4, 2014
• Est. completion date: February 27, 2016

Study information

• Verified date: June 2018
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Asia. The aim of the trial is to investigate safety and efficacy of semaglutide once weekly in monotherapy or in combination with one OAD (oral anti-diabetic drug) in Japanese subjects with type 2 diabetes who are insufficiently controlled on diet/exercise therapy or OAD monotherapy.

All subjects will continue their pre-trial treatment (diet and exercise therapy or OAD monotherapy in addition to diet and exercise therapy) during the trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 601
• Est. completion date: February 27, 2016
• Est. primary completion date: February 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Male or female, age at least 20 years at the time of signing informed consent

• HbA1c (glycosylated haemoglobin A1c) between 7.0% and 10.5% (53-91 mmol/mol) (both inclusive)

• Japanese subjects with type 2 diabetes mellitus (diagnosed clinically) and on stable treatment (defined as unchanged medication and unchanged dose) who are: a) on diet and exercise therapy for at least 30 days before Visit 1 (week -2). or b) on OAD monotherapy (either of SU (sulfonylurea), glinide, a-GI (a-glucosidase inhibitor) or TZD (thiazolidinediones)) within approved Japanese labelling in addition to diet and exercise therapy for at least 60 days before Visit 1 (week -2)

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 (e.g., abstinence [not having sex], diaphragm, condom [by the partner], intrauterine device, sponge, spermicide or oral contraceptives) throughout the trial including the 5 week follow-up period

• Treatment with glucose lowering agent(s) other than stated in the inclusion criteria within 60 days before Visit 1 (week -2) and treatment with once weekly glucagon-like peptide-1 (GLP-1) receptor agonists within 90 days before Visit 1 (week -2). An exception is short-term treatment (below or equal to 7 days in total) with insulin in connection with inter-current illness

• Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol

• 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 (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2)

• Impaired renal function defined as estimated glomerular filtration rate (eGFR) 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 (Visit 2 [week 0])

• Heart failure, New York Heart Association (NYHA) class IV

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• semaglutide
Subject will receive either a dose of 0.5 or 1.0 mg of semaglutide once weekly (subcutaneous (s.c.) injection).Treatment duration 56 weeks.
• DPP-4 inhibitor
Subjects will receive one DPP-4 inhibitor in addition to pre-trial OAD monotherapy, if any, for 56 weeks.

Locations

Country	Name	City	State
Japan	Novo Nordisk Investigational Site	Akita-shi, Akita
Japan	Novo Nordisk Investigational Site	Annaka-shi, Gunma
Japan	Novo Nordisk Investigational Site	Asahikawa-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Asahikawa-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Bunkyo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Chuo-ku Tokyo
Japan	Novo Nordisk Investigational Site	Chuo-ku Tokyo
Japan	Novo Nordisk Investigational Site	Chuo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Chuo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Chuo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Fukuoka
Japan	Novo Nordisk Investigational Site	Higashiosaka-shi, Osaka
Japan	Novo Nordisk Investigational Site	Izumisano-shi
Japan	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka
Japan	Novo Nordisk Investigational Site	Katsushika-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Kitakyushu-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Koriyama-shi, Fukushima
Japan	Novo Nordisk Investigational Site	Kumamoto-shi,Kumamoto
Japan	Novo Nordisk Investigational Site	Kyoto-shi, Kyoto
Japan	Novo Nordisk Investigational Site	Mito-shi, Ibaraki
Japan	Novo Nordisk Investigational Site	Miyazaki-shi
Japan	Novo Nordisk Investigational Site	Naka-shi, Ibaraki
Japan	Novo Nordisk Investigational Site	Nishinomiya-shi, Hygo
Japan	Novo Nordisk Investigational Site	Nishinomiya-shi, Hyogo
Japan	Novo Nordisk Investigational Site	Okawa-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Okayama-shi, Okayama
Japan	Novo Nordisk Investigational Site	Osaka-shi, Osaka
Japan	Novo Nordisk Investigational Site	Ota-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Ota-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Oyama-shi, Tochigi
Japan	Novo Nordisk Investigational Site	Saga-shi,Saga
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Sendai-shi
Japan	Novo Nordisk Investigational Site	Shimotsuke-shi, Tochigi
Japan	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Shizuoka-shi
Japan	Novo Nordisk Investigational Site	Suita-shi, Osaka
Japan	Novo Nordisk Investigational Site	Takatsuki-shi, Osaka
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Ube-shi, Yamaguchi
Japan	Novo Nordisk Investigational Site	Yokohama-shi

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Japan, 

References & Publications (3)

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. — View Citation

Kaku K, Yamada Y, Watada H, Abiko A, Nishida T, Zacho J, Kiyosue A. Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic drugs in Japanese people with inadequately controlled type 2 diabetes: A randomized trial. Diabetes Obes Met — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Treatment Emergent Adverse Events (TEAEs)	An adverse event (AEs) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).	Weeks 0-56
Secondary	Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia: was an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The episodes mentioned here are treatment emergent hypoglycaemic episodes and defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).	Weeks 0-56
Secondary	Change in Glycosylated Haemoglobin A1c (HbA1c)	The observed mean change in HbA1c values from baseline after 56 weeks of treatment. Changes in HbA1c were analysed using a mixed model for repeated measurements (MMRM) with treatment and pre-trial treatment at screening as fixed factors and baseline value as covariate. The data were analysed for the "on-treatment without rescue medication" observation period which includes observations noted at or after the date of first dose of randomised treatment and not after the last dose of the trial product (+ a 7-day visit window) or initiation of rescue medication.	Week 0, week 56

External Links

•   Clinical Trials at Novo Nordisk