A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Glargine, in People With Type 2 Diabetes Who Have Not Used Insulin Before

Diabetes Mellitus, Type 2 Clinical Trial

— ONWARDS 1  

Official title:

A 78-week Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Glargine 100 Units/mL, Both in Combination With Non-insulin Anti-diabetic Treatment, in Insulin naïve Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04460885
• Other study ID #: NN1436-4477
• Secondary ID: U1111-1247-38782
• Status: Completed
• Phase: Phase 3
• Start date: November 25, 2020
• Est. completion date: December 1, 2022

Study information

• Verified date: July 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 glargine (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 glargine 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 glargine 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 1 ½ years. Participants will have 37 clinic visits and 26 phone calls with the study doctor. At 11 clinic visits participant will have blood samples taken. At 8 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 the blood sugar all the time in 5 periods of about one month during the study (about 5 months in total). Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 984
• Est. completion date: December 1, 2022
• Est. primary completion date: May 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female aged above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus (T2D) 180 days or more prior to the day of screening.
• HbA1c from 7.0-11.0% (53.0-96.7 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
• Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
• Stable daily dose(s) 90 days or more prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s): a. Any metformin formulations at least or greater than 1500 mg or maximum tolerated or effective dose. b. Any metformin combination formulations equal to or above 1500 mg or maximum tolerated or effective dose. c. Any of the following oral anti-diabetic drug classes including combinations ((equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose): Sulfonylureas, Meglitinides (glinides), dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose co-transporter-2 (SGLT2) inhibitors, Thiazolidinediones, Alpha-glucosidase inhibitors, Oral combination products (for the allowed individual oral anti-diabetic drugs), Oral or injectable glucagon-like peptide 1 (GLP-1) receptor agonists
• Body mass index (BMI) equal to or below 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 icodec
Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 78 weeks.
• Insulin glargine
Participants will receive subcutaneous (s.c.) injections of insulin glargine once daily for 78 weeks

Locations

Country	Name	City	State
Croatia	Novo Nordisk Investigational Site	Karlovac
Croatia	Novo Nordisk Investigational Site	Osijek	Osjecko - Baranjska Županija
Croatia	Novo Nordisk Investigational Site	Rijeka
Croatia	Novo Nordisk Investigational Site	Varazdin
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Hyderabad	Telengana
India	Novo Nordisk Investigational Site	Hyderbad	Telengana
India	Novo Nordisk Investigational Site	Indore	Madhya Pradesh
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Rohtak	Haryana
India	Novo Nordisk Investigational Site	Vellore	Tamil Nadu
Israel	Novo Nordisk Investigational Site	Holon
Israel	Novo Nordisk Investigational Site	Jerusalem
Israel	Novo Nordisk Investigational Site	Kfar Saba
Israel	Novo Nordisk Investigational Site	Petach Tikva
Israel	Novo Nordisk Investigational Site	Rehovot
Italy	Novo Nordisk Investigational Site	Bergamo
Italy	Novo Nordisk Investigational Site	Catanzaro
Italy	Novo Nordisk Investigational Site	Milano
Italy	Novo Nordisk Investigational Site	Palermo
Italy	Novo Nordisk Investigational Site	Roma	RM
Japan	Novo Nordisk Investigational Site	Bunkyo-ku, Tokyo
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	Kitakyusyu-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Minato-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Miyagi
Japan	Novo Nordisk Investigational Site	Miyazaki-shi	Miyazaki, Japan
Japan	Novo Nordisk Investigational Site	Osaka
Japan	Novo Nordisk Investigational Site	Saitama
Japan	Novo Nordisk Investigational Site	Shimotsuke-shi, Tochigi
Japan	Novo Nordisk Investigational Site	Tochigi
Japan	Novo Nordisk Investigational Site	Ushiku-shi, Ibaraki
Mexico	Novo Nordisk Investigational Site	Guadalajara	Jalisco
Mexico	Novo Nordisk Investigational Site	Hermosillo	Sonora
Mexico	Novo Nordisk Investigational Site	Mexico City	México, D.F.
Mexico	Novo Nordisk Investigational Site	Monterrey	Nuevo León
Poland	Novo Nordisk Investigational Site	Bialystok	Podlaskie
Poland	Novo Nordisk Investigational Site	Gorzow Wielkopolski
Poland	Novo Nordisk Investigational Site	Lublin	Lubelskie
Poland	Novo Nordisk Investigational Site	Lublin	Lubelski
Poland	Novo Nordisk Investigational Site	Radom
Poland	Novo Nordisk Investigational Site	Warsaw	Mazowieckie
Poland	Novo Nordisk Investigational Site	Wierzchoslawice
Poland	Novo Nordisk Investigational Site	Zabrze
Puerto Rico	Novo Nordisk Investigational Site	Bayamon
Puerto Rico	Novo Nordisk Investigational Site	Manati
Russian Federation	Novo Nordisk Investigational Site	Kemerovo
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Penza
Russian Federation	Novo Nordisk Investigational Site	Saint Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Tomsk
Russian Federation	Novo Nordisk Investigational Site	Voronezh
Russian Federation	Novo Nordisk Investigational Site	Yoshkar-Ola
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Malacky
Slovakia	Novo Nordisk Investigational Site	Moldava nad Bodvou
Slovakia	Novo Nordisk Investigational Site	Sahy	Slovak Republic
Slovakia	Novo Nordisk Investigational Site	Trebisov
Spain	Novo Nordisk Investigational Site	La Coruña
Spain	Novo Nordisk Investigational Site	La Roca del Vallés
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Pozuelo de Alarcon
United Kingdom	Novo Nordisk Investigational Site	Blackpool
United Kingdom	Novo Nordisk Investigational Site	Bollington
United Kingdom	Novo Nordisk Investigational Site	Bradford-on-Avon
United Kingdom	Novo Nordisk Investigational Site	Bristol
United Kingdom	Novo Nordisk Investigational Site	Cambridge
United Kingdom	Novo Nordisk Investigational Site	Dorset
United Kingdom	Novo Nordisk Investigational Site	Edinburgh
United Kingdom	Novo Nordisk Investigational Site	Hinckley
United Kingdom	Novo Nordisk Investigational Site	Soham
United Kingdom	Novo Nordisk Investigational Site	Swansea
United Kingdom	Novo Nordisk Investigational Site	Truro
United Kingdom	Novo Nordisk Investigational Site	Wellingborough
United States	Novo Nordisk Investigational Site	Albuquerque	New Mexico
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Brooklyn	New York
United States	Novo Nordisk Investigational Site	Buena Park	California
United States	Novo Nordisk Investigational Site	Canton	Ohio
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	Fargo	North Dakota
United States	Novo Nordisk Investigational Site	Franklin	Ohio
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Greenville	North Carolina
United States	Novo Nordisk Investigational Site	Guntersville	Alabama
United States	Novo Nordisk Investigational Site	Gurnee	Illinois
United States	Novo Nordisk Investigational Site	Honolulu	Hawaii
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Hyattsville	Maryland
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Kingsport	Tennessee
United States	Novo Nordisk Investigational Site	Lampasas	Texas
United States	Novo Nordisk Investigational Site	Lancaster	California
United States	Novo Nordisk Investigational Site	Live Oak	Texas
United States	Novo Nordisk Investigational Site	Murrells Inlet	South Carolina
United States	Novo Nordisk Investigational Site	New Port Richey	Florida
United States	Novo Nordisk Investigational Site	Newport News	Virginia
United States	Novo Nordisk Investigational Site	Norman	Oklahoma
United States	Novo Nordisk Investigational Site	Omaha	Nebraska
United States	Novo Nordisk Investigational Site	Orlando	Florida
United States	Novo Nordisk Investigational Site	Paducah	Kentucky
United States	Novo Nordisk Investigational Site	Palm Harbor	Florida
United States	Novo Nordisk Investigational Site	Palm Springs	California
United States	Novo Nordisk Investigational Site	Raleigh	North Carolina
United States	Novo Nordisk Investigational Site	Renton	Washington
United States	Novo Nordisk Investigational Site	Rockville	Maryland
United States	Novo Nordisk Investigational Site	Round Rock	Texas
United States	Novo Nordisk Investigational Site	Saint George	Utah
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	Simpsonville	South Carolina
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Topeka	Kansas
United States	Novo Nordisk Investigational Site	Troy	Michigan
United States	Novo Nordisk Investigational Site	Ventura	California
United States	Novo Nordisk Investigational Site	Waterbury	Connecticut
United States	Novo Nordisk Investigational Site	West Des Moines	Iowa
United States	Novo Nordisk Investigational Site	West Palm Beach	Florida
United States	Novo Nordisk Investigational Site	West Seneca	New York
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,  Croatia,  India,  Israel,  Italy,  Japan,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Slovakia,  Spain,  United Kingdom, 

References & Publications (1)

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	%-point	From baseline week 0 (V2) to week 52 (V46)
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 48 (V42) to week 52 (V46)
Secondary	Change in fasting plasma glucose (FPG)	mmol/L	From baseline week 0 (V2) to week 52 (V46)
Secondary	Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 52 (V46)
Secondary	Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter)	Number of episodes	From baseline week 0 (V2) to week 52 (V46)
Secondary	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)	Number of episodes	From baseline week 0 (V2) to week 52 (V46)
Secondary	Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 83 (V63)
Secondary	Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter)	Number of episodes	From baseline week 0 (V2) to week 83 (V63)
Secondary	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)	Number of episodes	From baseline week 0 (V2) to week 83 (V63)
Secondary	Mean weekly insulin dose	U	From week 50 (V44) to week 52 (V46)
Secondary	Change in body weight	kg	From baseline week 0 (V2) to week 52 (V46)
Secondary	Time spent < 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	% of readings	From week 48 (V42) to week 52 (V46)
Secondary	Time spent > 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	% of readings	From week 48 (V42) to week 52 (V46)