A Research Study in People With Type 2 Diabetes to Compare Two Types of Insulin: Insulin 287 and Insulin Glargine

A Trial Comparing NNC0148-0287 C (Insulin 287) Versus Insulin Glargine U100, Both in Combination With Metformin, With or Without DPP4 Inhibitors and With or Without SGLT2 Inhibitors, in Basal Insulin Treated Subjects With Type 2 Diabetes Mellitus

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03922750

Enrollment

154

Registered

2019-04-22

Start date

2019-05-09

Completion date

2020-01-27

Last updated

2022-01-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

Brief summary

This study compares insulin 287 (a possible new medicine) to insulin glargine (a medicine doctors can already prescribe) in people with type 2 diabetes. Different ways of switching from the insulin which the participants are already on to insulin 287 are also compared. This is done to find the best way to switch to insulin 287. The participants will either get insulin 287 that they will have to inject once a week or insulin glargine that they will have to inject once a day. Which treatment any participant gets is decided by chance. The study will last for about 5 months (23 weeks). The participants will have 14 clinic visits and 6 phone calls with the study doctor. At 3 of the clinic visits participants will be asked not to eat or drink anything (except for water) in the last 8 hours before the visit. During the study, the doctor will ask the participants to: 1) measure their blood sugar every day with a blood sugar meter using a finger prick; 2) write down different information in a diary daily and return this to their study doctor. 3) wear a medical device (sensor) that measures the participants blood sugar all the time for 18 weeks (about 4 months) during the study.

Interventions

DRUGInsulin icodec

Participants will receive subcutaneous (s.c.) injections of Insulin 287 OW for 16 weeks.

DRUGInsulin glargine U100

Participants will receive s.c. injections of insulin glargine OD for 16 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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. * Glycosylated haemoglobin (HbA1c) of 7.0-10.0% (53.0-85.8 mmol/mol) (both inclusive) as assessed by central laboratory. * Treated with once daily or twice daily basal insulin analogue (insulin degludec, insulin detemir, insulin glargine U100 or U300, total daily dose of 10-50 U, both inclusive) greater than or equal to 90 days prior to the day of screening. * 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): 1. Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical records). 2. Free or fixed combination therapy: Metformin as outlined above with or without dipeptidyl peptidase 4 inhibitors (DPP4i) with or without sodium-glucose cotransporter 2 inhibitors (SGLT2i) is allowed: 1) DPP4i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose); 2) SGLT2i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose. * Body mass index (BMI) less than or equal to 40.0 kg/m\^2.

Exclusion criteria

* Known or suspected hypersensitivity to trial product(s) or related products. * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method. * Participation in any clinical trial of an approved or non-approved investigational medicinal product within 90 days before screening. * Any disorder, except for conditions associated with type 2 diabetes mellitus, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol. * Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation. * Known hypoglycaemic unawareness as indicated by the Investigator according to Clarke's questionnaire question 8. * Recurrent severe hypoglycaemic episodes within the last year as judged by the Investigator. * 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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Time in Target Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter (mg/dL)) Measured Using CGM (Continuous Glucose Monitoring)	During the last 2 weeks of treatment (week 15 and 16)	The percentage of time spent in glycaemic target range was calculated as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive divided by the total number of recorded measurements. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

Secondary

Measure	Time frame	Description
Change in Fasting Plasma Glucose (FPG)	From baseline week 0 (V2) to week 16 (V18)	Estimated mean change from baseline (week 0) in FPG at week 16 is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Change in Body Weight	From baseline week 0 (V2) to week 16 (V18)	Estimated mean change from baseline (week 0) in body weight at week 16 is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Weekly Insulin Dose	During the last 2 weeks of treatment (week 15 and 16)	Estimated mean average weekly insulin dose during the last 2 weeks of treatment is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Change in Glycosylated Haemoglobin (HbA1c)	From baseline week 0 (V2) to week 16 (V18)	Estimated mean change from baseline (week 0) in HbA1c at week 16 is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Number of Severe Hypoglycaemic Episodes (Level 3)	From baseline week 0 (V2) to week 16 (V18)	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 during weeks 0-16 are presented.
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)	From baseline week 0 (V2) to week 16 (V18)	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 \<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 occured during weeks 0-16 are presented.
Number of Hypoglycaemic Alert Episodes(Level 1) (Greater Than or Equal to 3.0 and Below 3.9 mmol/L (Greater Than or Equal to 54 and Below 70 mg/dL), Confirmed by BG Meter)	From baseline week 0 (V2) to week 16 (V18)	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. Number of hypoglycaemic alert episodes (level 1) (equal to or above 3.0 and below 3.9 mmol/L (equal to or above 54 and below 70 mg/dL), confirmed by BG meter) that occured during weeks 0-16 are presented.
Number of Treatment-emergent Adverse Events (TEAEs)	From baseline week 0 (V2) to week 21 (V20)	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 on-treatment observation period was the time period from 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. Safety analysis set (SAS) included all subjects exposed to at least one dose of trial product.

Countries

Canada, Czechia, Germany, Italy, United States

Participant flow

Recruitment details

The trial was conducted at 34 sites in 5 countries as follows: Canada (10), Italy (5), Czech Republic (4), Germany (5) and the United States (10). In addition, 3 sites in the United states and 1 site in Germany screened, but didn't randomise any subjects.

Pre-assignment details

Participants were randomised to receive once weekly insulin 287 using any of 2 different switch approaches or once daily insulin glargine; as an add-on to background therapy with basal insulin analogue with metformin, with or without dipeptidyl peptidase-4 inhibitors (DPP4i) and with or without sodium-glucose cotransporter 2 inhibitors (SGLT2i) at stable, pre-trial dose and at same frequency during the entire treatment period unless due to safety concerns related to the background medication.

Participants by arm

Arm	Count
Insulin 287 (Without Loading Dose) Participants were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: \< 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	50
Insulin 287 (With 100% Loading Dose) Participants were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective participants with additional loading dose ('unit to unit switch with an additional 100% loading dose' approach: current daily dose x 7 x 2). Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: \< 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: insulin dose increased by 28 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	54
Insulin Glargine U100 Participants were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. Participants were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: \< 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: insulin dose increased by 4 U. If the participant received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.	50
Total	154

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	0	1	0
Overall Study	Unclassified	0	0	1

Baseline characteristics

Characteristic	Insulin 287 (Without Loading Dose)	Insulin 287 (With 100% Loading Dose)	Insulin Glargine U100	Total
Age, Continuous	62.1 years STANDARD_DEVIATION 8.2	62.4 years STANDARD_DEVIATION 7.2	60.5 years STANDARD_DEVIATION 7.9	61.7 years STANDARD_DEVIATION 7.8
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	6 Participants	6 Participants	13 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants	48 Participants	44 Participants	141 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	9 Participants	4 Participants	3 Participants	16 Participants
Race (NIH/OMB) Black or African American	2 Participants	3 Participants	3 Participants	8 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	39 Participants	46 Participants	44 Participants	129 Participants
Sex: Female, Male Female	11 Participants	15 Participants	17 Participants	43 Participants
Sex: Female, Male Male	39 Participants	39 Participants	33 Participants	111 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 50	0 / 54	0 / 50
other Total, other adverse events	18 / 50	20 / 54	18 / 50
serious Total, serious adverse events	0 / 50	2 / 54	1 / 50

Outcome results

Primary

Percentage of Time in Target Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter (mg/dL)) Measured Using CGM (Continuous Glucose Monitoring)

The percentage of time spent in glycaemic target range was calculated as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive divided by the total number of recorded measurements. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

Time frame: During the last 2 weeks of treatment (week 15 and 16)

Population: Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Insulin 287 (Without Loading Dose)	Percentage of Time in Target Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter (mg/dL)) Measured Using CGM (Continuous Glucose Monitoring)	65.99 Percentage of time	Standard Error 2.34
Insulin 287 (With 100% Loading Dose)	Percentage of Time in Target Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter (mg/dL)) Measured Using CGM (Continuous Glucose Monitoring)	72.86 Percentage of time	Standard Error 2.13
Insulin Glargine U100	Percentage of Time in Target Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter (mg/dL)) Measured Using CGM (Continuous Glucose Monitoring)	64.98 Percentage of time	Standard Error 2.23

Comparison: The response and change from baseline in response during last two weeks of treatment (week 15 and 16) were analysed using an analysis of covariance (ANCOVA) model with treatment, pre-trial insulin treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values were imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset was analysed separately and estimates were combined using Rubin's rules.p-value: 0.754295% CI: [-5.33, 7.35]ANCOVA

Secondary

Change in Body Weight

Estimated mean change from baseline (week 0) in body weight at week 16 is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).