A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Use Daily Insulin

Diabetes Mellitus, Type 2 Clinical Trial

— ONWARDS 2  

Official title:

A 26-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Degludec, Both With or Without Non-insulin Anti-diabetic Drugs, in Subjects With Type 2 Diabetes Treated With Basal Insulin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04770532
• Other study ID #: NN1436-4478
• Secondary ID: U1111-1247-49452
• Status: Completed
• Phase: Phase 3
• Start date: March 5, 2021
• Est. completion date: March 1, 2022

Study information

• Verified date: May 2023
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study compares insulin icodec (a new insulin taken once a week) to insulin degludec (an insulin taken once daily which is already available on the market) in people with type 2 diabetes.

The study will look at how well insulin icodec taken weekly controls blood sugar compared to insulin degludec taken daily. Participants will either get insulin icodec that participants will have to inject once a week on the same day of the week or insulin degludec that participants will have to inject once a day at the same time every day. Which treatment participants get is decided by chance.

The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach.

The study will last for about 8 months. Participants will have 17 clinic visits and 13 phone calls with the study doctor. At 8 clinic visits participants will have blood samples taken. At 4 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit.

Participants will be asked to wear a sensor that measures their blood sugar all the time in 3 periods for a total of 13 weeks (about 3 months) during the study.

Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 526
• Est. completion date: March 1, 2022
• Est. primary completion date: January 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Male or female aged above or equal to 18 years at the time of signing informed consent.

• Diagnosed with T2D greater than or equal to 180 days prior to the day of screening.

• HbA1c from 7.0-10.0% (53.0 85.8 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.

• 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): greater than or equal to 90 days prior to the day of screening with or without any of the following anti-diabetic drugs/regimens with stable doses greater than or equal to 90 days prior to screening:

• Metformin

• Sulfonylureas

• Meglitinides (glinides)

• DPP-4 inhibitors

• SGLT2 inhibitors

• Thiazolidinediones

• Alpha-glucosidase inhibitors

• Oral combination products (for the allowed individual oral anti-diabetic drugs)

• Oral or injectable GLP-1-receptor agonists

• Body mass index (BMI) below or equal to 40.0 kg/m^2.

Exclusion Criteria:

• Any episodes (as declared by the subject or in the medical records) of diabetic ketoacidosis within 90 days prior to the day of screening.

• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.

• Chronic heart failure classified as being in New York Heart Association Class IV at screening.

• Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).

• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to 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 Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Insulin degludec
Participants will receive subcutaneous (s.c.) injections of insulin degludec once daily for 26 weeks
• Insulin Icodec
Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 26 weeks

Locations

Country	Name	City	State
Bulgaria	Novo Nordisk Investigational Site	Kyustendil
Bulgaria	Novo Nordisk Investigational Site	Plovdiv
Bulgaria	Novo Nordisk Investigational Site	Ruse
Bulgaria	Novo Nordisk Investigational Site	Sofia
Germany	Novo Nordisk Investigational Site	Essen
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Hohenmölsen
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Rehlingen-Siersburg
Germany	Novo Nordisk Investigational Site	Stuttgart
Germany	Novo Nordisk Investigational Site	Stuttgart
Japan	Novo Nordisk Investigational Site	Chiba
Japan	Novo Nordisk Investigational Site	Chigasaki-shi, Kanagawa	Kanagawa, Japan
Japan	Novo Nordisk Investigational Site	Fukuoka-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Ibaraki
Japan	Novo Nordisk Investigational Site	Miyazaki-shi	Miyazaki, Japan
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Tochigi
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Ushiku-shi, Ibaraki
Korea, Republic of	Novo Nordisk Investigational Site	Gyeonggi-do
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Poland	Novo Nordisk Investigational Site	Lodz
Poland	Novo Nordisk Investigational Site	Poznan
Poland	Novo Nordisk Investigational Site	Warszawa
Portugal	Novo Nordisk Investigational Site	Almada
Portugal	Novo Nordisk Investigational Site	Lisboa
Portugal	Novo Nordisk Investigational Site	Matosinhos
Portugal	Novo Nordisk Investigational Site	Porto
Portugal	Novo Nordisk Investigational Site	Porto
Portugal	Novo Nordisk Investigational Site	Vila Nova de Gaia
South Africa	Novo Nordisk Investigational Site	Bloemfontein	Free State
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape
Ukraine	Novo Nordisk Investigational Site	Dnipro
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Ternopil
United States	Novo Nordisk Investigational Site	Albany	New York
United States	Novo Nordisk Investigational Site	Amarillo	Texas
United States	Novo Nordisk Investigational Site	Buena Park	California
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Fort Worth	Texas
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Greensboro	North Carolina
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	La Jolla	California
United States	Novo Nordisk Investigational Site	Lincoln	California
United States	Novo Nordisk Investigational Site	New Orleans	Louisiana
United States	Novo Nordisk Investigational Site	Northridge	California
United States	Novo Nordisk Investigational Site	Ocala	Florida
United States	Novo Nordisk Investigational Site	Olympia	Washington
United States	Novo Nordisk Investigational Site	Palm Springs	California
United States	Novo Nordisk Investigational Site	Pembroke Pines	Florida
United States	Novo Nordisk Investigational Site	Rockville	Maryland
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	Slidell	Louisiana
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Valparaiso	Indiana
United States	Novo Nordisk Investigational Site	Waco	Texas
United States	Novo Nordisk Investigational Site	Walnut Creek	California
United States	Novo Nordisk Investigational Site	Waltham	Massachusetts
United States	Novo Nordisk Investigational Site	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Bulgaria,  Germany,  Japan,  Korea, Republic of,  Poland,  Portugal,  South Africa,  Ukraine, 

References & Publications (2)

Philis-Tsimikas A, Asong M, Franek E, Jia T, Rosenstock J, Stachlewska K, Watada H, Kellerer M. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, r — View Citation

Philis-Tsimikas A, Bajaj HS, Begtrup K, Cailleteau R, Gowda A, Lingvay I, Mathieu C, Russell-Jones D, Rosenstock J. Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes. Diabe — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c (glycated haemoglobin)	%-point	From baseline week 0 (V2) to week 26 (V28)
Secondary	Change in fasting plasma glucose (FPG)	mmol/L	From baseline week 0 (V2) to week 26 (V28)
Secondary	Time in target-range 3.9-10.0 mmol/L (70-180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	% of readings	From week 22 (V24) to week 26 (V28)
Secondary	Change in DTSQs (Diabetes Treatment Satisfaction Questionnaire) in total treatment satisfaction	Score 0-36 6 items scored on a scale of 0 to 6. The higher the score the greater the satisfaction with treatment	From baseline week 0 (V2) to week 26 (V28)
Secondary	Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 31 (V30)
Secondary	Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter)	Number of episodes	From baseline week 0 (V2) to week 31 (V30)
Secondary	Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 31 (V30)
Secondary	Time spent below 3.0 mmol/L (54 mg/dL) Using continuous glucose monitoring (CGM) system, Dexcom G6	% of readings	From week 22 (V24) to week 26 (V28)
Secondary	Time spent above 10 mmol/L (180 mg/dL) Using continuous glucose monitoring (CGM) system, Dexcom G6	% of readings	From week 22 (V24) to week 26 (V28)
Secondary	Mean weekly insulin dose	U	From week 24 (V26) to week 26 (V28)
Secondary	Change in body weight	kg	From baseline week 0 (V2) to week 26 (V28)