Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in the United States of America (USA). The aim of the trial is to confirm the efficacy of IDeg (insulin degludec) versus IGlar (insulin glargine) in controlling glycaemia. Subjects are to continue their pre-trial metformin treatment.
Interventions
DRUGinsulin degludec
Cross-over trial, part 1: Individually adjusted IDeg administered subcutaneously (s.c., under the skin) once daily for 16 weeks in each treatment period.
DRUGinsulin glargine
Cross-over trial, part 2: Individually adjusted IGlar administered subcutaneously (s.c., under the skin) once daily for the 16 week run-in period followed by 16 weeks in each treatment period.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * Current treatment with once daily insulin glargine in vials with a daily dose equal to or above 65 U and equal to or below 100 U * Current treatment with a stable dose of metformin plus/minus one additional oral antidiabetic drug (OAD) for at least 12 weeks * Glycosylated haemoglobin (HbA1c) equal to or above 7.5%
Exclusion criteria
* Current treatment with insulin other than insulin glargine in vials * Treatment with thiazolidinediones or glucagon-like peptide-1 (GLP-1) receptor agonists within 12 weeks * Stroke; heart failure; myocardial infarction; unstable angina pectoris; coronary arterial bypass graft or angioplasty * Suffer from cancer (except basal cell skin cancer and squamous-cell cancer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Visit 18) in Glycosylated Haemoglobin (HbA1c) at the End of Each 16 Week Treatment Period | Week 0, week 16 of each treatment period. | Values for change in HbA1c after each 16 weeks of treatment periods A and B. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period | Week 0, week 16 of each treatment period. | Changes in subjects quality of life and insulin device satisfaction were evaluated using the following PROs: the Short-Form 36 Health Survey version 2 (SF-36) and the Treatment Related Impact Measure-Diabetes Device (TRIM-DD). PRO total scores were measured from baseline to the end of each 16-week treatment period. Responses were measured on a scale of 0 to 100, where higher scores indicated a better quality of life and higher insulin device satisfaction on the SF-36 and TRIM-DD questionnaires, respectively. |
| Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | Week 16, week 20 | SF-36 and TRIM-DD total scores were measured at the end of treatment A (week 16) and 4 weeks into treatment B (week 20). Responses were measured on a scale of 0 to 100, where higher scores indicated a better quality of life and higher insulin device satisfaction on the SF-36 and TRIM-DD questionnaires, respectively. |
| Change From Baseline in Central Laboratory Measured Fasting Plasma Glucose (FPG) at the End of Each 16 Week Treatment Period | Week 0, week 16, week 32 | Values of FPG in mmol/L from baseline to each 16 weeks of treatment periods. |
| Change in FPG From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | Week 16, week 20 | Values of FPG in mmol/L from the end of treatment period A until after 4 weeks of treatment in treatment period B. |
| Number of Adverse Events (AEs) | From baseline to the end of each 16 week treatment period. | Number of treatment emergent adverse events (TEAEs) from week 0 to week 16 of the randomised treatment periods. A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. TEAEs were attributed to the treatment given in the period in which the event occurred. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
The trial was conducted at 37 sites in the United States of America (USA).
Pre-assignment details
All subjects were on insulin glargine (IGlar, ≥ 65 U and ≤ 100 U/mL in 10 mL vials) treatment once daily (OD) administered subcutaneously at any time of day preferred by the subject for 16 week run-in period along with the daily pre-trial metformin dose.
Participants by arm
| Arm | Count |
|---|---|
| IDeg/IGlar The subjects in this arm for treatment period A received IDeg OD (200 U/mL in pre-filled pen device) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IGlar OD (100 U/mL in SoloStar® pen) for 16 weeks (treatment period B). Subjects were crossed over to IGlar without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit. | 73 |
| IGlar/IDeg The subjects in this arm for treatment period A received IGlar OD (100 U/mL in SoloStar® pen) subcutaneously (under the skin) for 16 weeks (treatment period A) followed by IDeg OD (200 U/mL in pre-filled pen device) for 16 weeks (treatment period B). Subjects were crossed over to IDeg without a wash-out period between the two treatment sequences. Subjects continued on metformin (pre-trial dose) throughout the trial. There was a follow-up visit 7 days following the last treatment visit. | 72 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period A (16 Weeks) | Protocol Violation | 1 | 1 |
| Period A (16 Weeks) | Unclassified | 2 | 3 |
| Period A (16 Weeks) | Withdrawal criteria | 0 | 1 |
| Period B (16 Weeks) | Adverse Event | 1 | 0 |
| Period B (16 Weeks) | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | IDeg/IGlar | IGlar/IDeg | Total |
|---|---|---|---|
| Age, Continuous | 54.7 years STANDARD_DEVIATION 10.2 | 55.8 years STANDARD_DEVIATION 9 | 55.3 years STANDARD_DEVIATION 9.6 |
| Fasting plasma glucose (FPG) | 7.5 mmol/L STANDARD_DEVIATION 3.3 | 8.5 mmol/L STANDARD_DEVIATION 4.1 | 8.0 mmol/L STANDARD_DEVIATION 3.7 |
| Glycosylated haemoglobin (HbA1c) | 8.0 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.4 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.3 |
| Sex: Female, Male Female | 31 Participants | 24 Participants | 55 Participants |
| Sex: Female, Male Male | 42 Participants | 48 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 140 | 9 / 142 |
| serious Total, serious adverse events | 4 / 140 | 4 / 142 |
Outcome results
Primary
Change From Baseline (Visit 18) in Glycosylated Haemoglobin (HbA1c) at the End of Each 16 Week Treatment Period
Values for change in HbA1c after each 16 weeks of treatment periods A and B.
Time frame: Week 0, week 16 of each treatment period.
Population: The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF). For 7 subjects in IDeg treatment A and 7 subjects in IGlar treatment B, HbA1c values were missing at the period of baseline and did not contribute to the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Change From Baseline (Visit 18) in Glycosylated Haemoglobin (HbA1c) at the End of Each 16 Week Treatment Period | -0.1 percentage of glycosylated haemoglobin | Standard Deviation 1.1 |
| IGlar | Change From Baseline (Visit 18) in Glycosylated Haemoglobin (HbA1c) at the End of Each 16 Week Treatment Period | -0.1 percentage of glycosylated haemoglobin | Standard Deviation 1.1 |
Secondary
Change From Baseline in Central Laboratory Measured Fasting Plasma Glucose (FPG) at the End of Each 16 Week Treatment Period
Values of FPG in mmol/L from baseline to each 16 weeks of treatment periods.
Time frame: Week 0, week 16, week 32
Population: The FAS included all randomised subjects and missing data was imputed using LOCF. For 17 subjects in IDeg treatment A and 16 subjects in IGlar treatment B, FPG values were missing at the period of baseline and did not contribute to the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Change From Baseline in Central Laboratory Measured Fasting Plasma Glucose (FPG) at the End of Each 16 Week Treatment Period | -0.8 mmol/L | Standard Deviation 4.2 |
| IGlar | Change From Baseline in Central Laboratory Measured Fasting Plasma Glucose (FPG) at the End of Each 16 Week Treatment Period | -0.0 mmol/L | Standard Deviation 4.4 |
Secondary
Change in FPG From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B
Values of FPG in mmol/L from the end of treatment period A until after 4 weeks of treatment in treatment period B.
Time frame: Week 16, week 20
Population: The FAS included all randomised subjects and missing data was imputed using LOCF. For 19 subjects the FPG values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Change in FPG From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | -0.78 mmol/L | Standard Deviation 3.41 |
| IGlar | Change in FPG From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | 0.19 mmol/L | Standard Deviation 4.4 |
Secondary
Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period
Changes in subjects quality of life and insulin device satisfaction were evaluated using the following PROs: the Short-Form 36 Health Survey version 2 (SF-36) and the Treatment Related Impact Measure-Diabetes Device (TRIM-DD). PRO total scores were measured from baseline to the end of each 16-week treatment period. Responses were measured on a scale of 0 to 100, where higher scores indicated a better quality of life and higher insulin device satisfaction on the SF-36 and TRIM-DD questionnaires, respectively.
Time frame: Week 0, week 16 of each treatment period.
Population: The FAS included all randomised subjects and missing data was imputed using LOCF. For 8 subjects in each treatment group the values were missing at the period of baseline and did not contribute to the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IDeg | Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period | Physical score | -0.8 scores on a scale | Standard Deviation 7.7 |
| IDeg | Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period | Mental score | 0.7 scores on a scale | Standard Deviation 9.3 |
| IDeg | Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period | Total D-device | 11.0 scores on a scale | Standard Deviation 19.1 |
| IGlar | Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period | Physical score | -0.6 scores on a scale | Standard Deviation 7.8 |
| IGlar | Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period | Mental score | 0.4 scores on a scale | Standard Deviation 10.4 |
| IGlar | Change in Patient Reported Outcome (PRO) Scores From Baseline to the End of Each 16 Week Treatment Period | Total D-device | 3.5 scores on a scale | Standard Deviation 19.1 |
Secondary
Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B
SF-36 and TRIM-DD total scores were measured at the end of treatment A (week 16) and 4 weeks into treatment B (week 20). Responses were measured on a scale of 0 to 100, where higher scores indicated a better quality of life and higher insulin device satisfaction on the SF-36 and TRIM-DD questionnaires, respectively.
Time frame: Week 16, week 20
Population: The FAS included all randomised subjects. For 10 subjects, the PRO scores were missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IDeg | Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | Physical score | 0.02 scores on a scale | Standard Deviation 7.07 |
| IDeg | Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | Mental score | 0.61 scores on a scale | Standard Deviation 8.88 |
| IDeg | Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | Total D-device | 10.24 scores on a scale | Standard Deviation 19.89 |
| IGlar | Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | Physical score | 0.60 scores on a scale | Standard Deviation 6.09 |
| IGlar | Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | Mental score | 0.21 scores on a scale | Standard Deviation 8.59 |
| IGlar | Change in PRO Scores From the End of Treatment Period A Until After 4 Weeks of Treatment in Treatment Period B | Total D-device | -6.25 scores on a scale | Standard Deviation 11.1 |
Secondary
Number of Adverse Events (AEs)
Number of treatment emergent adverse events (TEAEs) from week 0 to week 16 of the randomised treatment periods. A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. TEAEs were attributed to the treatment given in the period in which the event occurred.
Time frame: From baseline to the end of each 16 week treatment period.
Population: The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg | Number of Adverse Events (AEs) | 105 events |
| IGlar | Number of Adverse Events (AEs) | 111 events |