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.

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03751657
• Other study ID #: NN1436-4383
• Secondary ID: U1111-1208-41242
• Status: Completed
• Phase: Phase 2
• Start date: November 29, 2018
• Est. completion date: January 17, 2020

Study information

• Verified date: March 2021
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 247
• Est. completion date: January 17, 2020
• Est. primary completion date: December 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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)
• Placebo (insulin 287)
Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287.
• Metformin
Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.
• 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.
• 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).
• Placebo (insulin glargine)
Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine.

Locations

Country	Name	City	State
Canada	Novo Nordisk Investigational Site	Brampton	Ontario
Canada	Novo Nordisk Investigational Site	Concord	Ontario
Canada	Novo Nordisk Investigational Site	Etobicoke	Ontario
Canada	Novo Nordisk Investigational Site	Halifax	Nova Scotia
Canada	Novo Nordisk Investigational Site	Hamilton	Ontario
Canada	Novo Nordisk Investigational Site	Sarnia	Ontario
Canada	Novo Nordisk Investigational Site	St-Marc-des-Carrières	Quebec
Czechia	Novo Nordisk Investigational Site	Brno
Czechia	Novo Nordisk Investigational Site	Pardubice
Czechia	Novo Nordisk Investigational Site	Praha
Czechia	Novo Nordisk Investigational Site	Praha 1
Czechia	Novo Nordisk Investigational Site	Praha 4
Czechia	Novo Nordisk Investigational Site	Praha 5
Czechia	Novo Nordisk Investigational Site	Praha 8
Czechia	Novo Nordisk Investigational Site	Rakovník
Czechia	Novo Nordisk Investigational Site	Slaný
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Poland	Novo Nordisk Investigational Site	Bialystok
Poland	Novo Nordisk Investigational Site	Gdansk
Poland	Novo Nordisk Investigational Site	Lodz
Poland	Novo Nordisk Investigational Site	Poznan
Poland	Novo Nordisk Investigational Site	Warsaw
Poland	Novo Nordisk Investigational Site	Wierzchoslawice
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Kosice
Slovakia	Novo Nordisk Investigational Site	Moldava nad Bodvou
Slovakia	Novo Nordisk Investigational Site	Sahy
Slovakia	Novo Nordisk Investigational Site	Trencin
Slovenia	Novo Nordisk Investigational Site	Koper
Slovenia	Novo Nordisk Investigational Site	Ljubljana
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Charlotte	North Carolina
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Lancaster	California
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Renton	Washington
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	Ventura	California
United States	Novo Nordisk Investigational Site	Walnut Creek	California
United States	Novo Nordisk Investigational Site	Whiteville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Greece,  Poland,  Slovakia,  Slovenia, 

References & Publications (1)

Rosenstock J, Bajaj HS, Janež 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/NEJMoa20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
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)	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)