A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3)

Diabetes Mellitus, Type 2 Clinical Trial

— ONWARDS 3  

Official title:

A 26-week Double Blinded, Multiregional, Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Degludec 100 Units/mL, Both in Combination With Non-insulin Anti-diabetic Drugs, in Insulin naïve Subjects With Type 2 Diabetes.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04795531
• Other study ID #: NN1436-4479
• Secondary ID: U1111-1247-52182
• Status: Completed
• Phase: Phase 3
• Start date: March 24, 2021
• Est. completion date: June 23, 2022

Study information

• Verified date: November 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 get their study medicine in an injection pen. Participants will get a pen for weekly injection and one for daily injection. One will be icodec or degludec and the other will be dummy medicine. The treatment participants get is decided by chance. Participants and the study staff will not know which active medicine they get.

The insulin is injected with a needle in a skin fold in the thigh. The study could last for about 8 months. Participants will have 13 clinic visits and 17 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 588
• Est. completion date: June 23, 2022
• Est. primary completion date: June 23, 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 T2D (type 2 diabetes) greater than or equal to 180 days prior to the day of screening.

• HbA1c (glycated haemoglobin) 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) greater than or equal to 90 days prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s):

a.) Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. b.) Any metformin combination formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. c.) Any of the following oral anti-diabetic drug classes including combinations (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose).:Sulfonylureas - Meglitinides (glinides) - DPP-4 inhibitors - SGLT2 inhibitors - Thiazolidinediones - Alpha-glucosidase inhibitors - Oral combination products (for the allowed individual Oral Anti-diabetic Drugs (OADs)) - 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 (NYHA) 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
You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo. Subcutaneously (under the skin) injections
• Placebo insulin icodec
You will get a pen for weekly injection and one for daily injection. One will be insulin degludec 100 units/mL and the other will be placebo. Subcutaneously (under the skin) injections
• Insulin degludec
You will get a pen for weekly injection and one for daily injection. One will be degludec 100 units/mL and the other will be placebo. Subcutaneously (under the skin) injections
• Placebo insulin degludec
You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo. Subcutaneously (under the skin) injections

Locations

Country	Name	City	State
Argentina	Novo Nordisk Investigational Site	Buenos Aires
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Mendoza
Austria	Novo Nordisk Investigational Site	Graz
Austria	Novo Nordisk Investigational Site	Linz
Austria	Novo Nordisk Investigational Site	Wien
Austria	Novo Nordisk Investigational Site	Wien
Brazil	Novo Nordisk Investigational Site	Curitiba	Parana
Brazil	Novo Nordisk Investigational Site	Curitiba	Parana
Brazil	Novo Nordisk Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novo Nordisk Investigational Site	São Paulo	Sao Paulo
Canada	Novo Nordisk Investigational Site	Barrie	Ontario
Canada	Novo Nordisk Investigational Site	Brampton	Ontario
Canada	Novo Nordisk Investigational Site	Brossard	Quebec
Canada	Novo Nordisk Investigational Site	Concord	Ontario
Canada	Novo Nordisk Investigational Site	Etobicoke	Ontario
Canada	Novo Nordisk Investigational Site	London	Ontario
Canada	Novo Nordisk Investigational Site	Montreal	Quebec
Canada	Novo Nordisk Investigational Site	Mount Pearl	Newfoundland and Labrador
Canada	Novo Nordisk Investigational Site	Nepean	Ontario
Canada	Novo Nordisk Investigational Site	Saint-Laurent	Quebec
Canada	Novo Nordisk Investigational Site	Sarnia	Ontario
Canada	Novo Nordisk Investigational Site	St. Johns	Newfoundland and Labrador
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Victoriaville	Quebec
China	Novo Nordisk Investigational Site	Beijing	Beijing
China	Novo Nordisk Investigational Site	Beijing	Beijing
China	Novo Nordisk Investigational Site	Cangzhou	Hebei
China	Novo Nordisk Investigational Site	Changzhou	Jiangsu
China	Novo Nordisk Investigational Site	ChongQing	Chongqing
China	Novo Nordisk Investigational Site	Hengshui	Hebei
China	Novo Nordisk Investigational Site	Jin'an	Shandong
China	Novo Nordisk Investigational Site	Nanjing	Jiangsu
China	Novo Nordisk Investigational Site	Nanjing	Jiangsu
China	Novo Nordisk Investigational Site	Shanghai	Shanghai
China	Novo Nordisk Investigational Site	Shanghai	Shanghai
China	Novo Nordisk Investigational Site	Tianjin	Tianjin
China	Novo Nordisk Investigational Site	Zhenjiang	Jiangsu
Czechia	Novo Nordisk Investigational Site	Broumov
Czechia	Novo Nordisk Investigational Site	Pardubice
Czechia	Novo Nordisk Investigational Site	Plzen 3
Czechia	Novo Nordisk Investigational Site	Praha 1
Czechia	Novo Nordisk Investigational Site	Praha 5
Czechia	Novo Nordisk Investigational Site	Praha 6
Denmark	Novo Nordisk Investigational Site	Aarhus N
Denmark	Novo Nordisk Investigational Site	Esbjerg
Denmark	Novo Nordisk Investigational Site	Hellerup
Denmark	Novo Nordisk Investigational Site	Hvidovre
France	Novo Nordisk Investigational Site	Le Coudray
France	Novo Nordisk Investigational Site	Narbonne
France	Novo Nordisk Investigational Site	Paris
France	Novo Nordisk Investigational Site	Pessac
France	Novo Nordisk Investigational Site	Pierre Benite
France	Novo Nordisk Investigational Site	Saint Herblain
France	Novo Nordisk Investigational Site	Toulouse
France	Novo Nordisk Investigational Site	Venissieux
Mexico	Novo Nordisk Investigational Site	Guadalajara	Jalisco
Mexico	Novo Nordisk Investigational Site	Hermosillo	Sonora
Puerto Rico	Novo Nordisk Investigational Site	Bayamon
Taiwan	Novo Nordisk Investigational Site	Changhua City
Taiwan	Novo Nordisk Investigational Site	Taichung
Taiwan	Novo Nordisk Investigational Site	Taichung City
Taiwan	Novo Nordisk Investigational Site	Tainan City
Taiwan	Novo Nordisk Investigational Site	Taipei
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	Escondido	California
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	Houston	Texas
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Lancaster	California
United States	Novo Nordisk Investigational Site	Norman	Oklahoma
United States	Novo Nordisk Investigational Site	Palm Harbor	Florida
United States	Novo Nordisk Investigational Site	Renton	Washington
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	Topeka	Kansas
United States	Novo Nordisk Investigational Site	Troy	Michigan
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,  Argentina,  Austria,  Brazil,  Canada,  China,  Czechia,  Denmark,  France,  Mexico,  Puerto Rico,  Taiwan, 

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 (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	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	Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 26 (V28)
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 26 (V28)
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 26 (V28)
Secondary	Change in body weight	Kg	From baseline week 0 (V2) to week 26 (V28)
Secondary	Mean weekly insulin dose	U	From week 24 (P26) to week 26 (V28)