A Research Study to Compare Insulin 287 Once a Week to Insulin Glargine (100 Units/mL) Once a Day in People With Type 2 Diabetes.

An Investigational Trial Comparing the Efficacy and Safety of Once Weekly NNC0148-0287 C (Insulin 287) Versus Once Daily Insulin Glargine, Both in Combination With Metformin, With or Without DPP-4 Inhibitors, in Insulin naïve Subjects With Type 2 Diabetes Mellitus

The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine) and insulin glargine (a medicine doctors can already prescribe). The study doctors will test insulin 287 to see how well it works compared to insulin glargine. The study will also test if insulin 287 is safe. The study participants will either get insulin 287 or insulin glargine (100 units/mL) - which treatment the participants get is decided by chance. The participants will need to inject their selves every day about the same time. Once a week the participant will need to take 1 extra injection on the same day of the week. The participants will have 16 clinic visits and 14 phone calls with the study doctor. During the study, the doctors will ask you to: 1) measure your blood sugar every day with a blood glucose meter using a finger prick, 2) write down different information in a paper diary daily and return this to your doctor, 3) wear a medical device to measure your blood sugar all the time for 2 weeks 5 times during the study.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin icodec; Drug: Metformin; Drug: Dipeptidyl peptidase-4 inhibitors; Drug: Placebo (insulin glargine); Drug: Placebo (insulin 287); Drug: Insulin glargine

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Novo Nordisk Investigational Site
  • Ontario
    • 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
    • Hamilton, Ontario, Canada, L8M 1K7
      • Novo Nordisk Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • Novo Nordisk Investigational Site
  • Quebec
    • St-Marc-des-Carrières, Quebec, Canada, G0A 4B0
      • Novo Nordisk Investigational Site
• Czechia
  • Brno, Czechia, 62500
    • Novo Nordisk Investigational Site
  • Pardubice, Czechia, 530 02
    • Novo Nordisk Investigational Site
  • Praha, Czechia, 128 08
    • Novo Nordisk Investigational Site
  • Praha 1, Czechia, 110 00
    • Novo Nordisk Investigational Site
  • Praha 4, Czechia, 149 00
    • Novo Nordisk Investigational Site
  • Praha 5, Czechia, 150 00
    • Novo Nordisk Investigational Site
  • Praha 8, Czechia, 181 00
    • Novo Nordisk Investigational Site
  • Rakovník, Czechia, 269 01
    • Novo Nordisk Investigational Site
  • Slaný, Czechia, 27401
    • Novo Nordisk Investigational Site
• Greece
  • Athens, Greece, GR-11527
    • Novo Nordisk Investigational Site
  • Athens, Greece, 115 25
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-54636
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-57010
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-54642
    • Novo Nordisk Investigational Site
• Poland
  • Bialystok, Poland, 15-404
    • Novo Nordisk Investigational Site
  • Gdansk, Poland, 80-546
    • Novo Nordisk Investigational Site
  • Lodz, Poland, 90-132
    • Novo Nordisk Investigational Site
  • Poznan, Poland, 61-251
    • Novo Nordisk Investigational Site
  • Warsaw, Poland, 00-465
    • Novo Nordisk Investigational Site
  • Wierzchoslawice, Poland, 33-122
    • Novo Nordisk Investigational Site
• Slovakia
  • Bratislava, Slovakia, 851 01
    • Novo Nordisk Investigational Site
  • Bratislava, Slovakia, 821 02
    • Novo Nordisk Investigational Site
  • Kosice, Slovakia, 040 01
    • Novo Nordisk Investigational Site
  • Moldava nad Bodvou, Slovakia, 045 01
    • Novo Nordisk Investigational Site
  • Sahy, Slovakia, 93601
    • Novo Nordisk Investigational Site
  • Trencin, Slovakia, 91101
    • Novo Nordisk Investigational Site
• Slovenia
  • Koper, Slovenia, SI-6000
    • Novo Nordisk Investigational Site
  • Ljubljana, Slovenia, SI-1000
    • Novo Nordisk Investigational Site
• United States
  • California
    • Lancaster, California, United States, 93534
      • Novo Nordisk Investigational Site
    • Ventura, California, United States, 93003
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Novo Nordisk Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Novo Nordisk Investigational Site
    • Whiteville, North Carolina, United States, 28472
      • Novo Nordisk Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Novo Nordisk Investigational Site
    • Chattanooga, Tennessee, United States, 37411
      • Novo Nordisk Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75390-9302
      • Novo Nordisk Investigational Site
  • Washington
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening
• HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory
• Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s): Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical record) OR Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject medical record) with Dipeptidyl peptidase-4 inhibitor (DPP4i) (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose (as documented in subject's medical records)
• 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
• Body mass index (BMI) less than or equal to 40.0 kg/m^2

Exclusion Criteria:

• Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation
• Presently classified as being in New York Heart Association (NYHA) Class IV
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. 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
• 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 pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation

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: Insulin 287; Participants will receive once weekly insulin 287 and once daily placebo in combination with metformin with or without dipeptidyl peptidase-4 inhibitors (DPP4i) during 26 weeks of treatment period.	Drug: Insulin icodec; Insulin 287 once weekly subcutaneous (s.c.) injections at the starting dose of 70 units. Dose adjustment was done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL); Other Names: Insulin 287; Drug: Metformin; Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.; Drug: Dipeptidyl peptidase-4 inhibitors; Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose.; Drug: Placebo (insulin glargine); Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine.
Active Comparator: Insulin glargine; Participants will receive once daily insulin glargine and once weekly placebo in combination with metformin with or without DPP4i during 26 weeks of treatment period.	Drug: Metformin; Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.; Drug: Dipeptidyl peptidase-4 inhibitors; Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose.; Drug: Placebo (insulin 287); Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287.; Drug: Insulin glargine; Insulin glargine (100 U/mL) once daily s.c. injections at the starting dose of 10 units. Dose adjustment will be done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]	Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	From baseline (Visit 2) to week 26 (Visit 28)
Change in HbA1c [Millimoles/Mole (mmol/Mol)]	Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	From baseline (Visit 2) to week 26 (Visit 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Plasma Glucose	Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	From baseline (Visit 2) to week 26 (Visit 28)
9-point Profile (Individual SMPG Values)	Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	Week 26 (Visit 28)
Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time	Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	From baseline (Visit 2) to week 26 (Visit 28)
Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).	Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	Week 26 (Visit 28)
Fasting C-peptide	Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	At week 26 (Visit 28)
Change in Body Weight	Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	From baseline (Visit 2) to week 26 (Visit 28)
Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine	Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.	week 25 (Visit 27) and 26 (Visit 28)
Number of Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.	From baseline (Visit 2) to week 31 (Visit 30)
Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter)	Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (>=) 3.0 and less than (<) 3.9 mmol/L (>= 54 and < 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.	From baseline (Visit 2) to week 26 (Visit 28)
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)	Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.	From baseline (Visit 2) to week 26 (Visit 28)
Number of Severe Hypoglycaemic Episodes (Level 3)	Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.	From baseline (Visit 2) to week 26 (Visit 28)
Change in Anti-insulin 287 Antibody Titres	Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.	From baseline (Visit 2) to week 31 (Visit 30)
Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)	Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.	From baseline (Visit 2) to week 31 (Visit 30)
Change in Anti-insulin 287 Antibody Level	Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.	From baseline (Visit 2) to week 31 (Visit 30)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Rosenstock J, Bajaj HS, Janez A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R; NN1436-4383 Investigators. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. N Engl J Med. 2020 Nov 26;383(22):2107-2116. doi: 10.1056/NEJMoa2022474. Epub 2020 Sep 22.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2018
• Primary Completion (Actual): December 16, 2019
• Study Completion (Actual): January 17, 2020

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 21, 2018
• First Posted (Actual): November 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 2, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: NN1436-4383; U1111-1208-4124 (Other Identifier: World Health Organization (WHO)); 2018-000322-63 (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