Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Europe. The aim of the trial is to compare insulin detemir once daily to NPH insulin once daily as measured by blood sugar control in ageing subjects with type 2 diabetes naive to previous insulin therapy.
Detailed description
Novo Nordisk has decided to discontinue the trial as it will not be possible to recruit the required number of patients. The discontinuation is based on an analysis of the significant delay in recruitment of patients which is likely to have a negative impact on the validity of the trial.
Interventions
DRUGinsulin detemir
Treat-to-target, s.c. (under the skin) injection, once daily
DRUGinsulin NPH
Treat-to-target, s.c. (under the skin) injection, once daily
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * Insulin naive * Treatment with oral anti-diabetic drugs (OADs) for at least 3 months and not achieving therapeutic targets * HbA1c between 8% - 10.5%
Exclusion criteria
* Secondary diabetes, MODY (Maturity Onset Diabetes of the Young) * Previous treatment with insulin (except for short-term treatment with insulin for intercurrent illness as judged by the Investigator) * Proliferative retinopathy, maculopathy requiring treatment, * Hypoglycaemia unawareness as judged by the Investigator, recurrent major hypoglycaemia * End stage liver disease (increased liver enzymes 4 fold), end stage renal disease assessed by MDRD (Modification of Diet in Renal Disease) less than 30 ml/min or dialysed patient, acute heart failure, any acute cardiovascular event or cerebrovascular event less than 6 months * Acute disease with poor prognosis * History of alcoholism, drug abuse, or psychiatric disease or personality disorders likely to invalidate voluntary consent or to prevent good compliance with the trial protocol * Mental incapacity, unwillingness or language barrier precluding adequate understanding or co-operation (patients having a score of less than 15 in a previous MMSE (Mini-Mental State Examination) in the last six months) and any conditions as judged by the investigator * Legal incapacity or limited legal capacity (patients under guardianship or curatorship) * Concomitant medication for Alzheimers treatment (Memantine, Anticholinesterasique treatment) * Participation in another clinical trial less than one month before inclusion in this trial * Illness requiring repeated hospitalisation * Known or suspected allergy to the insulin or any compositional component * Anticipated change or new use in concomitant medication known to interfere with glucose metabolism, such as systemic corticotherapy more than 5 mg/day (prednisone) * Any other condition that the Investigator feels would interfere with trial participation or evaluation of results * Terminal illness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) at Month 7 | week 0, month 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Fasting Plasma Glucose (FPG) at Month 7 | week 0, month 7 | — |
| Mean Number of Total Hypoglycaemic Episodes, Months 5-7 | weeks -2-0, months 5-7 | Mean number of total hypoglycaemic episodes per patient expressed as rate per week by visit. Rate per week is calculated by dividing the number of episodes for each patient by the number of weeks in the period. |
| Change in Mean Fasting Plasma Glucose (FPG) at Month 4 | week 0, month 4 | — |
| Change in Mean Pre-lunch Plasma Glucose at Month 7 | week 0, month 7 | — |
| Change in Mean Pre-lunch Plasma Glucose at Month 4 | week 0, month 4 | — |
| Change in Glycosylated Haemoglobin (HbA1c) at Month 4 | week 0, month 4 | — |
| Change in Mean Pre-dinner Plasma Glucose at Month 4 | week 0, month 4 | — |
| Change in Body Weight at Month 7 | week 0, month 7 | — |
| Change in Body Weight at Month 4 | week 0, month 4 | — |
| Mean Number of Total Hypoglycaemic Episodes, Month 1 | weeks -2-0, month 1 | Mean number of total hypoglycaemic episodes per patient expressed as rate per week by visit. Rate per week is calculated by dividing the number of episodes for each patient by the number of weeks in the period. |
| Mean Number of Total Hypoglycaemic Episodes, Months 2-4 | weeks -2-0, months 2-4 | Mean number of total hypoglycaemic episodes per patient expressed as rate per week by visit. Rate per week is calculated by dividing the number of episodes for each patient by the number of weeks in the period. |
| Change in Mean Pre-dinner Plasma Glucose at Month 7 | week 0, month 7 | — |
Countries
France, United Kingdom
Participant flow
Recruitment details
A total of 57 centres in 2 countries: France (35) and United Kingdom (22)
Pre-assignment details
Subjects in the trial were patients with type 2 diabetes being treated with oral anti-diabetic drug (OAD) therapy(ies) for at least 3 months prior to the trial and considered to benefit from insulin treatment. The randomisation target for this trial was 286.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Detemir Individually adjusted dose of insulin detemir once daily | 38 |
| Insulin NPH Individually adjusted dose of insulin NPH once daily | 48 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Not recorded | 4 | 6 |
| Overall Study | Protocol Violation | 2 | 4 |
| Overall Study | Trial terminated | 10 | 16 |
Baseline characteristics
| Characteristic | Insulin Detemir | Total | Insulin NPH |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 86 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 77.6 years STANDARD_DEVIATION 5.5 | 76.8 years STANDARD_DEVIATION 5.2 | 76.1 years STANDARD_DEVIATION 4.9 |
| Body Mass Index (BMI) | 29.1 kg/m^2 STANDARD_DEVIATION 4.6 | 29.5 kg/m^2 STANDARD_DEVIATION 5.1 | 29.8 kg/m^2 STANDARD_DEVIATION 5.5 |
| Duration of diabetes | 13.3 years STANDARD_DEVIATION 10.3 | 14.6 years STANDARD_DEVIATION 9.8 | 15.2 years STANDARD_DEVIATION 9.4 |
| Glycosylated Haemoglobin (HbA1c) | 9.26 percentage of total haemoglobin STANDARD_DEVIATION 0.87 | 9.19 percentage of total haemoglobin STANDARD_DEVIATION 0.82 | 9.12 percentage of total haemoglobin STANDARD_DEVIATION 0.78 |
| Sex: Female, Male Female | 21 Participants | 40 Participants | 19 Participants |
| Sex: Female, Male Male | 17 Participants | 46 Participants | 29 Participants |
| Weight | 77.4 kg STANDARD_DEVIATION 15.9 | 79.0 kg STANDARD_DEVIATION 16.2 | 80.4 kg STANDARD_DEVIATION 16.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 38 | 11 / 48 |
| serious Total, serious adverse events | 2 / 38 | 8 / 48 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c) at Month 7
Time frame: week 0, month 7
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Body Weight at Month 4
Time frame: week 0, month 4
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Body Weight at Month 7
Time frame: week 0, month 7
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Glycosylated Haemoglobin (HbA1c) at Month 4
Time frame: week 0, month 4
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Mean Fasting Plasma Glucose (FPG) at Month 4
Time frame: week 0, month 4
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Mean Fasting Plasma Glucose (FPG) at Month 7
Time frame: week 0, month 7
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Mean Pre-dinner Plasma Glucose at Month 4
Time frame: week 0, month 4
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Mean Pre-dinner Plasma Glucose at Month 7
Time frame: week 0, month 7
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Mean Pre-lunch Plasma Glucose at Month 4
Time frame: week 0, month 4
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Change in Mean Pre-lunch Plasma Glucose at Month 7
Time frame: week 0, month 7
Population: Due to the recruitment issue, the trial has been prematurely interrupted and the final number of patients does not allow any efficacy analysis.
Secondary
Mean Number of Total Hypoglycaemic Episodes, Month 1
Mean number of total hypoglycaemic episodes per patient expressed as rate per week by visit. Rate per week is calculated by dividing the number of episodes for each patient by the number of weeks in the period.
Time frame: weeks -2-0, month 1
Population: The safety analysis set is all patients who had been exposed to at least one dose of the trial product, and had hypoglycaemia data available at both endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Month 1 | Screening (week -2 to week 0) | 0.039 episodes per week by visit | Standard Deviation 0.179 |
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Month 1 | Month 1 (weeks 1-4) | 0.026 episodes per week by visit | Standard Deviation 0.097 |
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Month 1 | Difference (month 1-screening) | -0.013 episodes per week by visit | Standard Deviation 0.209 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Month 1 | Screening (week -2 to week 0) | 0.073 episodes per week by visit | Standard Deviation 0.372 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Month 1 | Month 1 (weeks 1-4) | 0.120 episodes per week by visit | Standard Deviation 0.282 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Month 1 | Difference (month 1-screening) | 0.047 episodes per week by visit | Standard Deviation 0.446 |
Secondary
Mean Number of Total Hypoglycaemic Episodes, Months 2-4
Mean number of total hypoglycaemic episodes per patient expressed as rate per week by visit. Rate per week is calculated by dividing the number of episodes for each patient by the number of weeks in the period.
Time frame: weeks -2-0, months 2-4
Population: The safety analysis set is all patients who had been exposed to at least one dose of the trial product, and had hypoglycaemia data available at both endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Months 2-4 | Screening (week -2 to week 0) | 0.039 episodes per week by visit | Standard Deviation 0.179 |
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Months 2-4 | Months 2-4 (weeks 5-16) | 0.015 episodes per week by visit | Standard Deviation 0.051 |
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Months 2-4 | Difference (months 2-4 - screening) | -0.024 episodes per week by visit | Standard Deviation 0.177 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Months 2-4 | Screening (week -2 to week 0) | 0.076 episodes per week by visit | Standard Deviation 0.38 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Months 2-4 | Months 2-4 (weeks 5-16) | 0.072 episodes per week by visit | Standard Deviation 0.167 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Months 2-4 | Difference (months 2-4 - screening) | -0.004 episodes per week by visit | Standard Deviation 0.394 |
Secondary
Mean Number of Total Hypoglycaemic Episodes, Months 5-7
Mean number of total hypoglycaemic episodes per patient expressed as rate per week by visit. Rate per week is calculated by dividing the number of episodes for each patient by the number of weeks in the period.
Time frame: weeks -2-0, months 5-7
Population: The safety analysis set is all patients who had been exposed to at least one dose of the trial product, and had hypoglycaemia data available at both endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Months 5-7 | Screening (week -2 to week 0) | 0.039 episodes per week by visit | Standard Deviation 0.179 |
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Months 5-7 | Months 5-7 (weeks 17-28) | 0.018 episodes per week by visit | Standard Deviation 0.078 |
| Insulin Detemir | Mean Number of Total Hypoglycaemic Episodes, Months 5-7 | Difference (months 5-7 - screening) | -0.022 episodes per week by visit | Standard Deviation 0.131 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Months 5-7 | Screening (week -2 to week 0) | 0.058 episodes per week by visit | Standard Deviation 0.381 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Months 5-7 | Months 5-7 (weeks 17-28) | 0.041 episodes per week by visit | Standard Deviation 0.099 |
| Insulin NPH | Mean Number of Total Hypoglycaemic Episodes, Months 5-7 | Difference (months 5-7 - screening) | -0.017 episodes per week by visit | Standard Deviation 0.4 |