A research study to see how well the new weekly medicine IcoSema, which is a combination of insulin icodec and semaglutide, controls blood sugar level in people with type 2 diabetes compared to weekly insulin icodec (COMBINE1)

JRCT ID: jRCT2031220146

Registered date:18/06/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: type 2 diabetes
• Date of first enrollment: 28/06/2022
• Target sample size: 120
• Countries of recruitment: Australia,Japan,Belgium,Japan,Bulgaria,Japan,China,Japan,Croatia,Japan,Finland,Japan,India,Japan,Italy,Japan,South Korea,Japan,Mexico,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,Romania,Japan,Russia,Japan,Serbia,Japan,South Africa,Japan,Taiwan,Japan,Turkey,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Participants will be randomised (1:1) to receive once weekly IcoSema or once weekly insulin icodec.

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

IcoSema should be taken once weekly at the same day of the week. The starting dose at randomisation (V2) will be 40 dose steps, which is equivalent to 40 units of insulin icodec and 0.114 mg of semaglutide. Then, the dose adjustment will be based on pre-breakfast SMPG values prior to the dose adjustment once weekly.

Insulin icodec should be taken once weekly at the same day of the week. All participants should receive a loading dose at randomisation (V2), which consist of total daily basal insulin dose before randomisation x 7 + 50% of their total daily basal insulin dose. The following weekly dose (V3) should be the total daily dose x 7. Then, the dose adjustment will be based on pre-breakfast SMPG values prior to the dose adjustment once weekly.

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)

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.

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: Takizaki Hiroshi