A 52-week study comparing the efficacy and safety of once weekly IcoSema and daily insulin glargine 100 units/mL combined with insulin aspart, both treatment arms with or without oral anti-diabetic drugs, in participants with type 2 diabetes inadequately controlled with daily basal insulin. (NN1535-4593:COMBINE 3)

JRCT ID: jRCT2051210127

Registered date:27/11/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: type 2 diabetes
• Date of first enrollment: 30/11/2021
• Target sample size: 80
• Countries of recruitment: Czech Republic,Japan,France,Japan,Germany,Japan,Hungary,,Japan,India,Japan,Italy,Japan,Malaysia,Japan,Poland,Japan,Slovenia,Japan,South Africa,Japan,Thailand,Japan,Turkey,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Participants will be randomised (1:1) to receive once weekly IcoSema or daily insulin glargine combined with 2-4 times daily injections of insulin aspart.

-an up to 2 weeks screening period
-a 52-week treatment period
- a 5-week follow-up period

Outcome(s)

• Primary Outcome: Change in HbA1c: From baseline week 0 (V2) to week 52 (V54)

Secondary Outcome

-Change in body weight: From baseline week 0 (V2) to week 52 (V54)
-Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3): From baseline week 0 (V2) to week 57 (V56)
-Weekly insulin dose (total): From week 50 (V52) to week 52 (V54)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Male or female and age above or equal to 18 years at the time of signing informed consent.
-Diagnosed with type 2 diabetes mellitus >= 180 days before screening.
-HbA1c of 7.0-10.0% (53.0-85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
-Treated with once daily or twice-daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20-80 units/day >= 90 days before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti-diabetic drugs with stable doses >=90 days before screening:
-Metformin
-Sulfonylureasa
-Meglitinides (glinides)
-DPP-4 inhibitors
-Sodium-glucose co-transporter 2 inhibitors
-Alpha-glucosidase-inhibitors
-Thiazolidinediones
-Marketed oral combination products only including the products listed above.
-Body mass index (BMI) <=40.0 kg/m2.

Exclude criteria

-Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
- Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or systemic corticosteroids).
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
- Any episodes of diabetic ketoacidosis within 90 days before screening.
- Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
- Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
- Chronic heart failure classified as being in New York Heart Association Class IV at screening.
- Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before 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.

Related Information

• Primary Sponsor: Miwa Hirotaka
• Secondary ID(s): NCT05013229,2020-005309-18