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) (ONWARDS 3)

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.

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin icodec; Drug: Placebo insulin degludec; Drug: Placebo insulin icodec; Drug: Insulin degludec

• Study Type: Interventional
• Enrollment (Actual): 588
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1023AAB
    • Novo Nordisk Investigational Site
  • Caba, Argentina, C1060ABA
    • Novo Nordisk Investigational Site
  • Caba, Argentina, C1440AAD
    • Novo Nordisk Investigational Site
  • Mendoza, Argentina, 5500
    • Novo Nordisk Investigational Site
• Austria
  • Graz, Austria, 8036
    • Novo Nordisk Investigational Site
  • Linz, Austria, 4021
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1120
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1140
    • Novo Nordisk Investigational Site
• Brazil
  • Parana
    • Curitiba, Parana, Brazil, 80045-170
      • Novo Nordisk Investigational Site
    • Curitiba, Parana, Brazil, 80810-040
      • Novo Nordisk Investigational Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90430-001
      • Novo Nordisk Investigational Site
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01228-000
      • Novo Nordisk Investigational Site
• Canada
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
      • Novo Nordisk Investigational Site
    • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
      • Novo Nordisk Investigational Site
  • Ontario
    • Barrie, Ontario, Canada, L4N 7L3
      • Novo Nordisk Investigational Site
    • Brampton, Ontario, Canada, L6S 0C6
      • Novo Nordisk Investigational Site
    • Concord, Ontario, Canada, L4K 4M2
      • Novo Nordisk Investigational Site
    • Etobicoke, Ontario, Canada, M9R 4E1
      • Novo Nordisk Investigational Site
    • London, Ontario, Canada, N6G 2M1
      • Novo Nordisk Investigational Site
    • Nepean, Ontario, Canada, K2J 0V2
      • Novo Nordisk Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M4G 3E8
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M9V 4B4
      • Novo Nordisk Investigational Site
  • Quebec
    • Brossard, Quebec, Canada, J4Z 2K9
      • Novo Nordisk Investigational Site
    • Montreal, Quebec, Canada, H1Y 3L1
      • Novo Nordisk Investigational Site
    • Saint-Laurent, Quebec, Canada, H4T 1Z9
      • Novo Nordisk Investigational Site
    • Victoriaville, Quebec, Canada, G6P 6P6
      • Novo Nordisk Investigational Site
• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 101200
      • Novo Nordisk Investigational Site
  • Chongqing
    • ChongQing, Chongqing, China, 404000
      • Novo Nordisk Investigational Site
  • Hebei
    • Cangzhou, Hebei, China, 061000
      • Novo Nordisk Investigational Site
    • Hengshui, Hebei, China, 053000
      • Novo Nordisk Investigational Site
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Novo Nordisk Investigational Site
    • Nanjing, Jiangsu, China, 210011
      • Novo Nordisk Investigational Site
    • Nanjing, Jiangsu, China, 211199
      • Novo Nordisk Investigational Site
    • Zhenjiang, Jiangsu, China, 212001
      • Novo Nordisk Investigational Site
  • Shandong
    • Jin'an, Shandong, China, 250013
      • Novo Nordisk Investigational Site
  • Shanghai
    • Shanghai, Shanghai, China, 200240
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200072
      • Novo Nordisk Investigational Site
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Novo Nordisk Investigational Site
• Czechia
  • Broumov, Czechia, 550 01
    • Novo Nordisk Investigational Site
  • Pardubice, Czechia, 530 02
    • Novo Nordisk Investigational Site
  • Plzeň 3, Czechia, 301 00
    • Novo Nordisk Investigational Site
  • Praha 1, Czechia, 110 00
    • Novo Nordisk Investigational Site
  • Praha 5, Czechia, 150 00
    • Novo Nordisk Investigational Site
  • Praha 6, Czechia, 160 00
    • Novo Nordisk Investigational Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Novo Nordisk Investigational Site
  • Esbjerg, Denmark, 6700
    • Novo Nordisk Investigational Site
  • Hellerup, Denmark, 2900
    • Novo Nordisk Investigational Site
  • Hvidovre, Denmark, 2650
    • Novo Nordisk Investigational Site
• France
  • Le Coudray, France, 28630
    • Novo Nordisk Investigational Site
  • Narbonne, France, 11100
    • Novo Nordisk Investigational Site
  • Paris, France, 75877
    • Novo Nordisk Investigational Site
  • Pessac, France, 33600
    • Novo Nordisk Investigational Site
  • Pierre Benite, France, 69310
    • Novo Nordisk Investigational Site
  • Saint Herblain, France, 44800
    • Novo Nordisk Investigational Site
  • Toulouse, France, 31054
    • Novo Nordisk Investigational Site
  • Venissieux, France, 69200
    • Novo Nordisk Investigational Site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Novo Nordisk Investigational Site
  • Sonora
    • Hermosillo, Sonora, Mexico, 83280
      • Novo Nordisk Investigational Site
• Puerto Rico
  • Bayamon, Puerto Rico, 00961
    • Novo Nordisk Investigational Site
• Taiwan
  • Changhua City, Taiwan, 500
    • Novo Nordisk Investigational Site
  • Taichung, Taiwan, 407
    • Novo Nordisk Investigational Site
  • Taichung City, Taiwan, 402
    • Novo Nordisk Investigational Site
  • Tainan City, Taiwan, 710
    • Novo Nordisk Investigational Site
  • Taipei, Taiwan, 112
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Guntersville, Alabama, United States, 35976
      • Novo Nordisk Investigational Site
  • California
    • Buena Park, California, United States, 90620
      • Novo Nordisk Investigational Site
    • Escondido, California, United States, 92025
      • Novo Nordisk Investigational Site
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • Lancaster, California, United States, 93534
      • Novo Nordisk Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Novo Nordisk Investigational Site
    • Palm Harbor, Florida, United States, 34684-3609
      • Novo Nordisk Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Novo Nordisk Investigational Site
  • Kansas
    • Topeka, Kansas, United States, 66606-2806
      • Novo Nordisk Investigational Site
  • Michigan
    • Troy, Michigan, United States, 48098
      • Novo Nordisk Investigational Site
  • New York
    • West Seneca, New York, United States, 14224
      • Novo Nordisk Investigational Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Novo Nordisk Investigational Site
    • Wilmington, North Carolina, United States, 28401
      • Novo Nordisk Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Novo Nordisk Investigational Site
    • Dayton, Ohio, United States, 45439
      • Novo Nordisk Investigational Site
    • Franklin, Ohio, United States, 45005
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Novo Nordisk Investigational Site
  • South Carolina
    • Simpsonville, South Carolina, United States, 29681-1538
      • Novo Nordisk Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75390-9302
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77024
      • Novo Nordisk Investigational Site
    • Round Rock, Texas, United States, 78681
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78229
      • Novo Nordisk Investigational Site
  • Utah
    • Saint George, Utah, United States, 84790
      • Novo Nordisk Investigational Site
  • Washington
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Once weekly insulin icodec + once daily placebo; Participants will get once daily and once weekly injections	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; Drug: 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
Experimental: Once weekly placebo and once daily insulin degludec; Participants will get once daily and once weekly injections	Drug: 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; Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c (glycated haemoglobin)	%-point	From baseline week 0 (V2) to week 26 (V28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasting plasma glucose (FPG)	mmol/L	From baseline week 0 (V2) to week 26 (V28)
Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 31 (V30)
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)
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)
Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 26 (V28)
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)
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)
Change in body weight	Kg	From baseline week 0 (V2) to week 26 (V28)
Mean weekly insulin dose	U	From week 24 (P26) to week 26 (V28)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• 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. Diabetes Obes Metab. 2023 Feb;25(2):331-341. doi: 10.1111/dom.14871. Epub 2022 Oct 14.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Actual): June 23, 2022
• Study Completion (Actual): June 23, 2022

Study Registration Dates

• First Submitted: March 10, 2021
• First Submitted That Met QC Criteria: March 10, 2021
• First Posted (Actual): March 12, 2021

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin, Long-Acting
• Other Study ID Numbers: NN1436-4479; U1111-1247-5218 (Other Identifier: World Health Organization (WHO)); 2020-000472-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No