Diabetes Mellitus, Type 2
Conditions
Brief summary
To compare glycemic control and treatment satisfaction using a novel bolus insulin patch (Finesse) versus a pen for initiating and managing bolus insulin dosing in patients with T2DM not achieving glycemic targets on basal insulin with/without anti-hyperglycemic agents.
Detailed description
Patients sub-optimally controlled on basal insulin (with/without other antihyperglycemic agents (AHAs)) will be randomized 1:1 to either Finesse or pen to initiate bolus insulin dosing and followed for a 44-week intervention period. Patients will have both basal and bolus doses of insulin adjusted throughout the trial, as is clinically indicated, based on an easy to follow insulin dosing algorithm. After the final endpoint evaluation at week 44, patients will crossover to the alternate bolus insulin delivery device for 4 weeks and complete a patient preference survey at week 48.
Interventions
DEVICEBolus Insulin Patch (Calibra Finesse)
DEVICEInsulin Pen (Novo-Nordisk FlexPen®)
Sponsors
Medpace, Inc.
Calibra Medical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of T2DM * Treated with basal insulin for ≥ 6 months, with current dose stable for ≥ 6 weeks of ≥ 0.3 U/kg/day, with or without anti-hyperglycemic agents and in whom the Investigator feels advancement from basal to basal and bolus therapy is needed for the patient * A1C 7.5-11.0% by central lab value at screening visit * Already perform self-monitoring of blood glucose (SMBG) and willing to test blood glucose (BG) over the course of the study * Body Mass Index of ≤ 40 kg/m2
Exclusion criteria
* Currently on or has been treated in the past year with insulin regimens that include bolus insulins except the need for insulins in the settings of acute illness or hospitalization * History of type 1 diabetes mellitus (T1DM), or diabetic ketoacidosis (DKA), or secondary forms of diabetes such as cystic fibrosis * Known hypersensitivity or allergy to insulin-glargine or its excipients or any other insulins * Two or more severe hypoglycemic episodes within the prior year * Hypoglycemia unawareness defined by history * History of proliferative diabetic retinopathy * Is currently unstable and/or has moderate-to-severe medical illness in the Investigator's judgment * Uncontrolled hypertension (either treated or untreated) defined as a systolic blood pressure ≥ 160 mmHg or a diastolic blood pressure ≥ 100 mmHg at screening * History of recent major surgery within 6 months, or minor surgery within 3 months (such as appendectomy) prior to screening visit, or a planned surgery during the study period * History of bariatric surgery * Active chronic infections * Women of child-bearing age who are pregnant, planning pregnancy, breast-feeding, or, if capable of pregnancy, are not practicing contraception if heterosexually active * Known hypersensitivity to plastics/polymers/adhesives * Known difficulties with adherence of adhesives, bandages, or dressings * Participated in any research study within the past 30 days * Currently participating in another investigational trial * Use of short term or chronic systemic steroids within three months of entry into the study or likelihood that same might be required during the conduct of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in A1C From Baseline to the Completion of 24 Weeks of Basal and Bolus Insulin Therapy | 24 weeks | Change in A1C, with bolus insulin dosing with patch versus pen, from baseline to the completion of 24 weeks of basal and bolus insulin therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in A1C From Week 24 to Week 44 | 44 weeks | Change in A1C from week 24 to week 44 after basal and bolus insulin therapy |
| Number of Patients With A1C ≤7.0% at Week 24 | 24 weeks | Number of patients with A1C ≤7.0% at week 24 |
| Change in Percent of Glucose Values of Continuous Glucose Monitoring (CGM) Measurements Within Targeted Range of 71 and 180 mg/dl (4.0 and 10.0 mmol/l) From Baseline to Week 24 | 24 weeks | Change in percent of glucose values of Continuous Glucose Monitoring (CGM) measurements within targeted range of 71 and 180 mg/dl (4.0 and 10.0 mmol/l) from baseline to week 24 (in a subset of patients) |
| Number of Patients With A1C ≤7.0% at Week 44 | 44 weeks | Number of patients with A1C ≤7.0% after 44 weeks of basal and bolus insulin therapy |
| Number of Participants With Severe Hypoglycemic Event | 44 weeks | An event requiring the assistance of another person to actively administer carbohydrate (including IV dextrose), glucagon, or other resuscitative actions. Neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. |
| Change in A1C From Baseline to Week 44 | 44 weeks | Change in A1C from baseline to the completion of 44 weeks of basal and bolus insulin therapy |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Treatment Satisfaction From Baseline to Week 24 | 24 weeks | Change in treatment satisfaction with insulin delivery system from baseline to week 24 was assessed by self-report on the validated Insulin Delivery System Rating Questionnaire. Scale is 0-100. Higher score is better. |
| Change in Quality of Life From Baseline to Week 24 | 24 weeks | Change in Diabetes-Specific Quality of Life (QOL), baseline to week 24. was assessed by self-report on the validated Diabetes Specific Quality of Life Survey. Scale is 0-100. Higher score is better. |
Countries
France, Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bolus Insulin Patch Experimental Treatment Arm | 139 |
| Insulin Pen Comparator Treatment Arm | 139 |
| Total | 278 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 6 | 5 |
| Overall Study | Other | 2 | 1 |
| Overall Study | Physician Decision | 6 | 4 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Sponsor Termination | 1 | 0 |
| Overall Study | Used Prohibited Medication | 2 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 16 |
Baseline characteristics
| Characteristic | Total | Insulin Pen | Bolus Insulin Patch |
|---|---|---|---|
| A1C | 8.7 A1C % STANDARD_DEVIATION 1 | 8.7 A1C % STANDARD_DEVIATION 1 | 8.6 A1C % STANDARD_DEVIATION 0.9 |
| Age, Continuous | 59.2 years STANDARD_DEVIATION 8.9 | 60.4 years STANDARD_DEVIATION 7.9 | 58.1 years STANDARD_DEVIATION 9.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 11 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 246 Participants | 126 Participants | 120 Participants |
| Sex: Female, Male Female | 110 Participants | 52 Participants | 58 Participants |
| Sex: Female, Male Male | 168 Participants | 87 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 139 | 2 / 139 |
| other Total, other adverse events | 100 / 139 | 99 / 139 |
| serious Total, serious adverse events | 10 / 139 | 13 / 139 |
Outcome results
Primary
Change in A1C From Baseline to the Completion of 24 Weeks of Basal and Bolus Insulin Therapy
Change in A1C, with bolus insulin dosing with patch versus pen, from baseline to the completion of 24 weeks of basal and bolus insulin therapy
Time frame: 24 weeks
Population: The primary outcome measure analysis used a modified intent-to-treat (mITT) population data set which included all the intent-to-treat (ITT) patients who had a baseline A1C and at least one post-baseline A1C measurement. For missing values, the last observation carried forward (LOCF) imputation method was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bolus Insulin Patch | Change in A1C From Baseline to the Completion of 24 Weeks of Basal and Bolus Insulin Therapy | -1.69 A1C % | Standard Error 0.08 |
| Insulin Pen | Change in A1C From Baseline to the Completion of 24 Weeks of Basal and Bolus Insulin Therapy | -1.60 A1C % | Standard Error 0.08 |
p-value: <0.000195% CI: [-0.32, 0.14]ANCOVA
Secondary
Change in A1C From Baseline to Week 44
Change in A1C from baseline to the completion of 44 weeks of basal and bolus insulin therapy
Time frame: 44 weeks
Population: Only patients with non-missing baseline and endpoint values were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bolus Insulin Patch | Change in A1C From Baseline to Week 44 | -1.63 A1C % | Standard Error 0.1 |
| Insulin Pen | Change in A1C From Baseline to Week 44 | -1.63 A1C % | Standard Error 0.1 |
p-value: 0.9995% CI: [-0.28, 0.28]ANCOVA
Secondary
Change in A1C From Week 24 to Week 44
Change in A1C from week 24 to week 44 after basal and bolus insulin therapy
Time frame: 44 weeks
Population: Only patients with non-missing week 24 and week 44 values were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bolus Insulin Patch | Change in A1C From Week 24 to Week 44 | 0.12 A1C % | Standard Error 0.06 |
| Insulin Pen | Change in A1C From Week 24 to Week 44 | 0.07 A1C % | Standard Error 0.06 |
p-value: 0.5295% CI: [-0.12, 0.24]ANCOVA
Secondary
Change in Percent of Glucose Values of Continuous Glucose Monitoring (CGM) Measurements Within Targeted Range of 71 and 180 mg/dl (4.0 and 10.0 mmol/l) From Baseline to Week 24
Change in percent of glucose values of Continuous Glucose Monitoring (CGM) measurements within targeted range of 71 and 180 mg/dl (4.0 and 10.0 mmol/l) from baseline to week 24 (in a subset of patients)
Time frame: 24 weeks
Population: Modified intent-to-treat population data subset.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bolus Insulin Patch | Change in Percent of Glucose Values of Continuous Glucose Monitoring (CGM) Measurements Within Targeted Range of 71 and 180 mg/dl (4.0 and 10.0 mmol/l) From Baseline to Week 24 | 26.87 % of glucose values | Standard Error 2.33 |
| Insulin Pen | Change in Percent of Glucose Values of Continuous Glucose Monitoring (CGM) Measurements Within Targeted Range of 71 and 180 mg/dl (4.0 and 10.0 mmol/l) From Baseline to Week 24 | 29.84 % of glucose values | Standard Error 2.4 |
p-value: 0.3895% CI: [-9.63, 3.7]ANCOVA
Secondary
Number of Participants With Severe Hypoglycemic Event
An event requiring the assistance of another person to actively administer carbohydrate (including IV dextrose), glucagon, or other resuscitative actions. Neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time frame: 44 weeks
Population: Intent to Treat. All patients randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bolus Insulin Patch | Number of Participants With Severe Hypoglycemic Event | 3 Participants |
| Insulin Pen | Number of Participants With Severe Hypoglycemic Event | 3 Participants |
p-value: 1Chi-squared
Secondary
Number of Patients With A1C ≤7.0% at Week 24
Number of patients with A1C ≤7.0% at week 24
Time frame: 24 weeks
Population: Modified intent-to-treat (mITT) population data set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bolus Insulin Patch | Number of Patients With A1C ≤7.0% at Week 24 | 85 Participants |
| Insulin Pen | Number of Patients With A1C ≤7.0% at Week 24 | 77 Participants |
p-value: 0.2695% CI: [0.81, 2.14]Cochran-Mantel-Haenszel
Secondary
Number of Patients With A1C ≤7.0% at Week 44
Number of patients with A1C ≤7.0% after 44 weeks of basal and bolus insulin therapy
Time frame: 44 weeks
Population: Only patients with non-missing baseline and endpoint values were included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bolus Insulin Patch | Number of Patients With A1C ≤7.0% at Week 44 | 70 Participants |
| Insulin Pen | Number of Patients With A1C ≤7.0% at Week 44 | 68 Participants |
p-value: 0.7195% CI: [0.64, 1.93]Cochran-Mantel-Haenszel
Other Pre-specified
Change in Quality of Life From Baseline to Week 24
Change in Diabetes-Specific Quality of Life (QOL), baseline to week 24. was assessed by self-report on the validated Diabetes Specific Quality of Life Survey. Scale is 0-100. Higher score is better.
Time frame: 24 weeks
Population: Per Protocol. Only patients with non-missing baseline and endpoint values were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bolus Insulin Patch | Change in Quality of Life From Baseline to Week 24 | 2.37 units on a scale | Standard Error 1.43 |
| Insulin Pen | Change in Quality of Life From Baseline to Week 24 | -1.95 units on a scale | Standard Error 1.44 |
p-value: 0.0395% CI: [0.33, 8.32]ANCOVA
Other Pre-specified
Change in Treatment Satisfaction From Baseline to Week 24
Change in treatment satisfaction with insulin delivery system from baseline to week 24 was assessed by self-report on the validated Insulin Delivery System Rating Questionnaire. Scale is 0-100. Higher score is better.
Time frame: 24 weeks
Population: Per Protocol. Only patients with non-missing baseline and endpoint values were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bolus Insulin Patch | Change in Treatment Satisfaction From Baseline to Week 24 | 13.63 units on a scale | Standard Error 1.94 |
| Insulin Pen | Change in Treatment Satisfaction From Baseline to Week 24 | 4.47 units on a scale | Standard Error 2.01 |
p-value: 0.00195% CI: [3.65, 14.67]ANCOVA