A Research Study to Compare Two Types of Insulin: Insulin 287 and Insulin Glargine in People With Type 2 Diabetes Who Have Not Used Insulin Before

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 Insulin-naïve Subjects With Type 2 Diabetes Mellitus

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03951805

Enrollment

205

Registered

2019-05-15

Start date

2019-05-09

Completion date

2020-01-17

Last updated

2021-04-05

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 changing the dose of insulin 287 are also compared. This is done to find the best way to change the dose of insulin 287. Participants will either get insulin 287 that they will have to inject once a week or insulin glargine that participants will have to inject once a day. Which treatment participants get is decided by chance. The study will last for about 5 months (23 weeks). 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 study doctor will ask participants to: * measure blood sugar every day with a blood sugar meter using a finger prick. * write down different information in a diary daily and return this to the study doctor. * wear a medical device (sensor) that measure blood sugar all the time for 18 weeks (about 4 months) during the study. Women cannot take part if pregnant, breastfeeding or plan to become pregnant during the study period.

Interventions

DRUGInsulin icodec

Administered subcutaneously SC once weekly. Starting dose will be 70U.

DRUGInsulin Glargine

Administered subcutaneously SC once daily.The starting dose will be 10U.

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 * HbA1c of 7.0-10.0% (53.0-85.8 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): 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 plus/minus DPP4i with or without SGLT2i is allowed: i) DPP4i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose) ii) SGLT2i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose ) * 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) below or equal to 40.0 kg/m\^2

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Time in Target Range (TIR) 3.9-10.0 Millimoles Per Liter (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 considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). The endpoint is based on data recorded by CGM system. It was required that at least 70% of the planned CGM measurements during weeks 15-16 were available for endpoint data to be included in the analysis.

Secondary

Measure	Time frame	Description
Change in Fasting Plasma Glucose (FPG)	From baseline week 0 (visit 2) to week 16 (visit 18)	Estimated mean change in FPG from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) 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 considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Change in Body Weight	From baseline week 0 (visit 2) to week 16 (visit 18)	Estimated mean change in body weight from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) 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 considered exposed to 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 considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
Change in HbA1c (Glycated Haemoglobin)	From baseline week 0 (visit 2) to week 16 (visit 18)	Estimated mean change in HbA1c from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) 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 considered exposed to 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 (visit 2) to week 16 (visit 18)	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 baseline (week 0, visit 2) to end of treatment (week 16, visit 18) are presented.
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose (BG) Meter) or Severe Hypoglycaemic Episodes (Level 3)	From baseline week 0 (visit 2) to week 16 (visit 18)	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 occured from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) 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 Blood Glucose (BG) Meter)	From baseline week 0 (visit 2) to week 16 (visit 18)	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 \< 3.9 mmol/L (\>= 54 and \< 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occured from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) are presented.
Number of Treatment Emergent Adverse Events (TEAEs)	From baseline week 0 (visit 2) to week 21 (visit 20)	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 (week 0, visit 2) until the follow-up visit (week 21, visit 20) or the last date on trial product + 5 weeks for once daily insulin and +6 weeks for once weekly insulin.

Countries

Croatia, Germany, Hungary, Poland, Slovakia, Spain, United States

Participant flow

Recruitment details

The trial was conducted at 38 sites in 7 countries as follows: Croatia (4), Germany (9), Hungary (3), Poland (4), Slovakia (5), Spain (4), United States (9). In addition, 1 site in Slovakia and 3 sites in the United States screened, but didn't randomise any subjects.

Pre-assignment details

Participants were randomised to receive once weekly insulin 287 using one of 3 different titration algorithms (A, B, C), or once daily insulin glargine (titration algorithm D); as add-on to background therapy with metformin with or without dipeptidyl peptidase-4 inhibitors (DPP4i) and with or without sodium-glucose cotransporter 2 inhibitors (SGLT2i).

Participants by arm

Arm	Count
Insulin 287 (Titration Algorithm A) 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 70 units (U). The dose was adjusted weekly during the treatment period using titration algorithm A with American Diabetes Association (ADA) glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: \< 4.4 mmol/L: insulin dose reduced by 21 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: insulin dose increased by 21 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.	51
Insulin 287 (Titration Algorithm B) 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 70 U. The dose was adjusted weekly during the treatment period using titration algorithm B with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: \< 4.4 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication	51
Insulin 287 (Titration Algorithm C) 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 70 U. The dose was adjusted weekly during the treatment period using titration algorithm C with glycaemic target of 3.9-6.0 mmol/L (70-108 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: \< 3.9 mmol/L: insulin dose reduced by 28 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 3.9-6.0 mmol/L: no adjustment; \> 6.0 mmol/L: insulin dose increased by 28 U. All participants used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.	52
Insulin Glargine (Titration Algorithm D) Subjects were to receive once daily s.c. injection of Insulin glargine for 16 weeks, using SoloSTAR pre-filled pen-injector at a starting dose of 10 U. The dose was adjusted weekly during the treatment period using titration algorithm D with ADA glycaemic target of 4.4-7.2 mmol/L (80-130 mg/dL), based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the contact. If at least one pre-breakfast SMPG value was: \< 4.4 mmol/L: insulin dose reduced by 4 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was between 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: insulin dose increased by 4 U. All subjects used metformin with or without DPP4i and with or without SGLT2i at the stable, pre-trial dose and at the same frequency during the entire treatment period unless due to safety concerns related to the background medication.	51
Total	205

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	1	0	0	0

Baseline characteristics

Characteristic	Insulin 287 (Titration Algorithm A)	Total	Insulin Glargine (Titration Algorithm D)	Insulin 287 (Titration Algorithm C)	Insulin 287 (Titration Algorithm B)
Age, Continuous	59.8 years STANDARD_DEVIATION 9.1	60.7 years STANDARD_DEVIATION 8.3	60.2 years STANDARD_DEVIATION 8.1	61.4 years STANDARD_DEVIATION 8	61.2 years STANDARD_DEVIATION 8
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	12 Participants	3 Participants	2 Participants	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants	193 Participants	48 Participants	50 Participants	46 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants	1 participants	1 participants	0 participants	0 participants
Race/Ethnicity, Customized Asian	0 participants	2 participants	0 participants	0 participants	2 participants
Race/Ethnicity, Customized Black or African American	0 participants	2 participants	1 participants	1 participants	0 participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants	1 participants	1 participants	0 participants	0 participants
Race/Ethnicity, Customized other	0 participants	1 participants	1 participants	0 participants	0 participants
Race/Ethnicity, Customized White	51 participants	198 participants	47 participants	51 participants	49 participants
Sex: Female, Male Female	24 Participants	95 Participants	24 Participants	24 Participants	23 Participants
Sex: Female, Male Male	27 Participants	110 Participants	27 Participants	28 Participants	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 51	0 / 51	0 / 52	0 / 51
other Total, other adverse events	9 / 51	10 / 51	7 / 52	9 / 51
serious Total, serious adverse events	3 / 51	1 / 51	0 / 52	2 / 51

Outcome results

Primary

Percentage of Time in Target Range (TIR) 3.9-10.0 Millimoles Per Liter (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 considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). The endpoint is based on data recorded by CGM system. It was required that at least 70% of the planned CGM measurements during weeks 15-16 were available for endpoint data to be included in the analysis.

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 = Number of participants who contributed to the analysis.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Insulin 287 (Titration Algorithm A)	Percentage of Time in Target Range (TIR) 3.9-10.0 Millimoles Per Liter (mmol/L) (70-180 Milligrams Per Deciliter (mg/dL) Measured Using CGM (Continuous Glucose Monitoring)	76.65 Percentage of time	Standard Error 1.81
Insulin 287 (Titration Algorithm B)	Percentage of Time in Target Range (TIR) 3.9-10.0 Millimoles Per Liter (mmol/L) (70-180 Milligrams Per Deciliter (mg/dL) Measured Using CGM (Continuous Glucose Monitoring)	82.97 Percentage of time	Standard Error 1.8
Insulin 287 (Titration Algorithm C)	Percentage of Time in Target Range (TIR) 3.9-10.0 Millimoles Per Liter (mmol/L) (70-180 Milligrams Per Deciliter (mg/dL) Measured Using CGM (Continuous Glucose Monitoring)	80.89 Percentage of time	Standard Error 1.81
Insulin Glargine (Titration Algorithm D)	Percentage of Time in Target Range (TIR) 3.9-10.0 Millimoles Per Liter (mmol/L) (70-180 Milligrams Per Deciliter (mg/dL) Measured Using CGM (Continuous Glucose Monitoring)	75.89 Percentage of time	Standard Error 1.82

Comparison: The response and change from baseline in response during the last two weeks of treatment (week 15 and 16) are analysed using an analysis of covariance (ANCOVA) model with treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values are imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset is analysed separately and estimates are combined using Rubin's rules.p-value: 0.767595% CI: [-4.28, 5.8]ANCOVA

Secondary

Change in Body Weight

Estimated mean change in body weight from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) 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 considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).