Type 1 Diabetes Mellitus
Conditions
Brief summary
Open-label, randomized, forced-titration clinical trial evaluating the efficacy and safety of TI Inhalation Power in combination with a basal insulin versus insulin aspart in combination with a basal insulin
Detailed description
Phase 3 clinical trial designed to examine the efficacy and safety of inhaled prandial TI Inhalation Power in combination with basal insulin versus insulin aspart in combination with basal insulin in subjects with type 1 diabetes who are suboptimally controlled with their current insulin regimens. This trial will employ a variety of methods to intensively manage these subjects.
Interventions
DRUGTechnosphere® Insulin with MedTone C Inhaler
Inhalation Powder and injectable insulin
DRUGTechnosphere ®Insulin with Gen2 Inhaler
Inhalation Powder and injectable insulin
DRUGInsulin Aspart in combination with a basal insulin
Injectable insulin
Sponsors
Mannkind Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women = 18 years of age * Clinical diagnosis of type 1 diabetes mellitus for at least 12 months * Body mass index (BMI) = 38 kg/m2 * Stable dose of basal/bolus insulin therapy for at least 3 months with an FPG consistently \< 220 mg/dL: * HbA1c = 7.5% and = 10.0% * Fasting C-peptide = 0.30 pmol/mL * Subject willingness to not use CGM during the entire course of the trial * Nonsmoking (includes cigarettes, cigars, pipes, and chewing tobacco) for the preceding 6 months * Negative urine cotinine test, defined as = 100 ng/mL * Lung function tests: • Forced expiratory volume in 1 second (FEV1) = 70% Third National Health and Nutrition Examination Survey (NHANES III) predicted * Written informed consent
Exclusion criteria
* Total daily insulin dose = 2 IU/kg/day. History of insulin pump use within 3 months of Screening or use of continuous glucose monitoring within 6 weeks of Screening * History of inhaled insulin use in the previous 6 months * Two or more unexplained severe hypoglycemic episodes within 3 months of Screening or an episode of severe hypoglycemia between Visit 1 and Visit 2. Unexplained refers to episodes of severe hypoglycemia that are not related to a dosing error, lack of or a change in meal size, or related to additional/unanticipated exercise * Any hospitalization or emergency room visit due to poor diabetic control within 6 months of Screening, or hospitalization or emergency room visit due to poor diabetic control between Visit 1 and Visit 2 * Allergy or known hypersensitivity to insulin or to any of the drugs to be used in the study, or a history of hypersensitivity to TI Inhalation Powder or to drugs with a similar chemical structure * History of recent blood transfusions (within previous 3 months), hemoglobinopathies, or any other conditions that affect HbA1c measurements. * History of COPD, asthma, or any other clinically important pulmonary disease (eg, pulmonary fibrosis), or use of any medications for these conditions * Any clinically significant radiological findings on screening chest x-ray * Active respiratory infection within 30 days before Screening (subject may return after 30 days from resolution for rescreening) * Major organ system diseases, including: ? Seizure disorder; systemic autoimmune or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine; cancer (other than excised cutaneous basal cell carcinoma) or any history of lung neoplasms * Current or previous chemotherapy or radiation therapy that may result in pulmonary toxicity; use of medications for weight loss (eg, sibutramine, orlistat) within 12 weeks of Screening; treatment with amiodarone within 12 weeks of Screening * Clinically significant abnormalities on screening laboratory evaluation or chest x-ray * Severe complications of diabetes, in the opinion of the PI, including symptomatic autonomic neuropathy; disabling peripheral neuropathy; active proliferative retinopathy; nephropathy with renal failure, renal transplant, or dialysis; nontraumatic amputations due to gangrene; or vascular claudication * Women who are pregnant, lactating, or planning to become pregnant during the clinical study period; women of childbearing potential (defined as premenopausal and not surgically sterilized or postmenopausal for fewer than 2 years) not practicing adequate birth control. Adequate birth control is defined as using oral, percutaneous, or transdermal contraceptives; condoms and diaphragms (double barrier) with a spermicide; or intrauterine devices. Postmenopausal for this study includes amenorrhea f * Current drug or alcohol abuse or a history of drug or alcohol abuse that, in the opinion of the PI, would make the subject an unsuitable candidate for participation in the study * Exposure to any investigational medications or devices within the previous 30 days before study entry * Unable to read or write, or unlikely to comprehend and follow the study protocol procedures; lack of compliance with medication or procedures that, in the PI's opinion, may affect the study data or subject safety and that precludes the subject from participation in the study; or any other concurrent medical or major psychiatric condition that, in the opinion of the PI, makes the subject unsuitable for the clinical study or could limit the validity of the informed consent or impair the subject'
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in HbA1c | Baseline to Week 24 | Effect of treatment as measured by change from baseline in glycated hemoglobin (HbA1c). Primary treatment difference is TI-Gen2 vs. Insulin Aspart at Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FPG Change From Baseline to Week 24 | Baseline to Week 24 | Comparison of mean change from Baseline to Week 24 visit in fasting plasma glucose (FPG) levels (central laboratory results) |
| Mean 7-point Glucose Baseline Values | Baseline | Mean 7-point glucose at baseline |
| Mean 7-point Glucose Week 24 Values | Week 24 | — |
| Change in Body Weight From Baseline to Week 24 | Baseline to Week 24 | Change in body weight from Baseline to Week 24 |
| Proportion of Responders Achieving HbA1c <= 7.0% | Week 24 | Efficacy as measured in proportion of subjects achieving HbA1c \< or = to 7.0% |
| FEV1 Change From Baseline to Week 24 | Baseline to Week 24 | Forced Expiratory Volume in 1 second - change from baseline to week 24 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Total Hypoglycemia | Baseline to Week 24 | Hypoglycemia, defined as blood glucose \<= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates. |
| Incidence of Severe Hypoglycemia | Baseline to Week 24 | Severe Hypoglycemia defined as: Requiring 3rd party assistance. |
| Total Hypoglycemia Event Rate | Baseline to Week 24 | Number of Hypoglycemic Events/Total Subject Exposure Time (in months) |
| Severe Hypoglycemia Event Rate | Baseline to Week 24 | Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months) |
Countries
Brazil, Russia, Ukraine, United States
Participant flow
Recruitment details
First Patient enrolled Sept 2011. Multi-national trial conducted in US, Russia, Ukraine and Brazil.
Pre-assignment details
3 week Screening Period prior to run-in (basal insulin optimization period). 1401 Screened / 621 Eligible of which 614 entered the run-in period. 538 met randomization criteria at end of run-in of which 518 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient | 174 |
| Technosphere Insulin-MedTone + Basal Insulin Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient | 174 |
| Insulin Aspart + Basal Insulin Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient | 170 |
| Total | 518 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 9 | 0 |
| Overall Study | Cough | 0 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 | 4 |
| Overall Study | Non-compliance with protocol | 0 | 1 | 0 |
| Overall Study | Non-compliance with study drug | 1 | 2 | 0 |
| Overall Study | Physician Decision | 3 | 1 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 4 |
| Overall Study | Protocol Violation | 2 | 2 | 2 |
| Overall Study | Sponsor decision - subject travel | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 21 | 16 | 8 |
Baseline characteristics
| Characteristic | Technosphere Insulin-MedTone + Basal Insulin | Total | Technosphere Insulin-Gen2 + Basal Insulin | Insulin Aspart + Basal Insulin |
|---|---|---|---|---|
| Age, Customized 18-30 years | 48 participants | 150 participants | 56 participants | 46 participants |
| Age, Customized 31-49 years | 84 participants | 265 participants | 93 participants | 88 participants |
| Age, Customized 50-64 years | 33 participants | 79 participants | 18 participants | 28 participants |
| Age, Customized >= 65 years | 9 participants | 24 participants | 7 participants | 8 participants |
| BMI | 26.2 kg/m^2 | 25.9 kg/m^2 | 26.0 kg/m^2 | 25.4 kg/m^2 |
| Duration of Diabetes | 17.7 years | 16.8 years | 16.0 years | 16.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 57 Participants | 17 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 152 Participants | 461 Participants | 157 Participants | 152 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting Plasma Glucose | 144.3 mg/dL | 150.2 mg/dL | 155.0 mg/dL | 151.2 mg/dL |
| HbA1c | 8.00 Percent of hemoglobin | 7.95 Percent of hemoglobin | 7.98 Percent of hemoglobin | 7.88 Percent of hemoglobin |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 16 Participants | 8 Participants | 3 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 | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 167 Participants | 497 Participants | 164 Participants | 166 Participants |
| Region of Enrollment Brazil | 15 participants | 42 participants | 14 participants | 13 participants |
| Region of Enrollment Russian Federation | 52 participants | 149 participants | 45 participants | 52 participants |
| Region of Enrollment Ukraine | 38 participants | 120 participants | 44 participants | 38 participants |
| Region of Enrollment United States | 69 participants | 207 participants | 71 participants | 67 participants |
| Sex: Female, Male Female | 94 Participants | 287 Participants | 97 Participants | 96 Participants |
| Sex: Female, Male Male | 80 Participants | 231 Participants | 77 Participants | 74 Participants |
| Weight | 76.8 kg | 75.1 kg | 75.7 kg | 72.6 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 81 / 174 | 74 / 173 | 50 / 171 |
| serious Total, serious adverse events | 5 / 174 | 9 / 173 | 7 / 171 |
Outcome results
Primary
Change From Baseline to Week 24 in HbA1c
Effect of treatment as measured by change from baseline in glycated hemoglobin (HbA1c). Primary treatment difference is TI-Gen2 vs. Insulin Aspart at Week 24
Time frame: Baseline to Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Change From Baseline to Week 24 in HbA1c | -0.21 Percent of hemoglobin | Standard Error 0.062 |
| Technosphere Insulin-MedTone + Basal Insulin | Change From Baseline to Week 24 in HbA1c | -0.29 Percent of hemoglobin | Standard Error 0.061 |
| Insulin Aspart + Basal Insulin | Change From Baseline to Week 24 in HbA1c | -0.40 Percent of hemoglobin | Standard Error 0.06 |
Comparison: MMRM (mixed model repeated measures) model with auto-regression (1): HbA1c = Baseline HbA1c + region + basal insulin stratum + visit + treatment + (visit\*treatment)95% CI: [0.02, 0.36]
Secondary
Change in Body Weight From Baseline to Week 24
Change in body weight from Baseline to Week 24
Time frame: Baseline to Week 24
Population: Full analysis set (subjects with data available at Baseline and at Week 24)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Change in Body Weight From Baseline to Week 24 | -0.39 kg | Standard Error 0.438 |
| Technosphere Insulin-MedTone + Basal Insulin | Change in Body Weight From Baseline to Week 24 | -0.19 kg | Standard Error 0.428 |
| Insulin Aspart + Basal Insulin | Change in Body Weight From Baseline to Week 24 | 0.93 kg | Standard Error 0.441 |
p-value: 0.010295% CI: [-2.33, -0.31]ANCOVA
Comparison: Within treatment analysis of change from Baseline comparing if change was different from zerop-value: 0.4955t-test, 2 sided
Comparison: Within treatment analysis of change from Baseline comparing if change was different from zerop-value: 0.6807t-test, 2 sided
Comparison: Within treatment analysis of change from Baseline comparing if change was different from zerop-value: 0.0079t-test, 2 sided
Secondary
FEV1 Change From Baseline to Week 24
Forced Expiratory Volume in 1 second - change from baseline to week 24
Time frame: Baseline to Week 24
Population: Safety population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | FEV1 Change From Baseline to Week 24 | -0.07 Liters | Standard Error 0.012 |
| Technosphere Insulin-MedTone + Basal Insulin | FEV1 Change From Baseline to Week 24 | -0.08 Liters | Standard Error 0.012 |
| Insulin Aspart + Basal Insulin | FEV1 Change From Baseline to Week 24 | -0.04 Liters | Standard Error 0.011 |
95% CI: [-0.02, 0.04]
Secondary
FPG Change From Baseline to Week 24
Comparison of mean change from Baseline to Week 24 visit in fasting plasma glucose (FPG) levels (central laboratory results)
Time frame: Baseline to Week 24
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | FPG Change From Baseline to Week 24 | -25.27 mg/dL | Standard Error 7.62 |
| Technosphere Insulin-MedTone + Basal Insulin | FPG Change From Baseline to Week 24 | 7.15 mg/dL | Standard Error 7.53 |
| Insulin Aspart + Basal Insulin | FPG Change From Baseline to Week 24 | 10.15 mg/dL | Standard Error 7.4 |
95% CI: [-56.25, -14.59]
Secondary
Mean 7-point Glucose Baseline Values
Mean 7-point glucose at baseline
Time frame: Baseline
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Baseline Values | Before dinner | 169.9 mg/dL | Standard Deviation 47.12 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Baseline Values | Before lunch | 158.0 mg/dL | Standard Deviation 47.39 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Baseline Values | Bedtime | 178.3 mg/dL | Standard Deviation 51.38 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Baseline Values | After lunch | 169.5 mg/dL | Standard Deviation 52.25 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Baseline Values | After dinner | 176.2 mg/dL | Standard Deviation 51.55 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Baseline Values | After breakfast | 173.3 mg/dL | Standard Deviation 48.77 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Baseline Values | Before breakfast | 154.1 mg/dL | Standard Deviation 38.85 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Baseline Values | Bedtime | 175.1 mg/dL | Standard Deviation 43.99 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Baseline Values | Before breakfast | 151.8 mg/dL | Standard Deviation 40.32 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Baseline Values | After breakfast | 173.5 mg/dL | Standard Deviation 48.36 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Baseline Values | Before lunch | 156.6 mg/dL | Standard Deviation 42.91 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Baseline Values | After lunch | 169.7 mg/dL | Standard Deviation 49.23 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Baseline Values | Before dinner | 168.1 mg/dL | Standard Deviation 45.24 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Baseline Values | After dinner | 177.0 mg/dL | Standard Deviation 53.17 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Baseline Values | After breakfast | 162.6 mg/dL | Standard Deviation 49.5 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Baseline Values | After dinner | 158.5 mg/dL | Standard Deviation 47.64 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Baseline Values | Before dinner | 154.0 mg/dL | Standard Deviation 46.53 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Baseline Values | Before breakfast | 147.0 mg/dL | Standard Deviation 39.09 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Baseline Values | Before lunch | 142.3 mg/dL | Standard Deviation 37.86 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Baseline Values | Bedtime | 164.4 mg/dL | Standard Deviation 49.97 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Baseline Values | After lunch | 157.6 mg/dL | Standard Deviation 48.08 |
Secondary
Mean 7-point Glucose Week 24 Values
Time frame: Week 24
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Week 24 Values | After breakfast | 169.7 mg/dL | Standard Deviation 67.53 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before dinner | 177.8 mg/dL | Standard Deviation 59.96 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Week 24 Values | After lunch | 173.7 mg/dL | Standard Deviation 57.09 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before breakfast | 148.2 mg/dL | Standard Deviation 40.64 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Week 24 Values | Bedtime | 185.2 mg/dL | Standard Deviation 62.36 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Week 24 Values | After dinner | 180.8 mg/dL | Standard Deviation 63.5 |
| Technosphere Insulin-Gen2 + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before lunch | 168.2 mg/dL | Standard Deviation 56.93 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Week 24 Values | After lunch | 163.1 mg/dL | Standard Deviation 50.92 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before breakfast | 147.9 mg/dL | Standard Deviation 43.17 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Week 24 Values | After breakfast | 164.1 mg/dL | Standard Deviation 60.97 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before lunch | 165.9 mg/dL | Standard Deviation 59.95 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before dinner | 177.3 mg/dL | Standard Deviation 56.71 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Week 24 Values | After dinner | 168.2 mg/dL | Standard Deviation 60.77 |
| Technosphere Insulin-MedTone + Basal Insulin | Mean 7-point Glucose Week 24 Values | Bedtime | 185.6 mg/dL | Standard Deviation 54.96 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before dinner | 156.8 mg/dL | Standard Deviation 48.3 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Week 24 Values | After breakfast | 163.0 mg/dL | Standard Deviation 58 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Week 24 Values | Bedtime | 175.4 mg/dL | Standard Deviation 57.37 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Week 24 Values | After dinner | 157.8 mg/dL | Standard Deviation 52.62 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Week 24 Values | After lunch | 158.2 mg/dL | Standard Deviation 50.04 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before lunch | 149.1 mg/dL | Standard Deviation 50.58 |
| Insulin Aspart + Basal Insulin | Mean 7-point Glucose Week 24 Values | Before breakfast | 155.3 mg/dL | Standard Deviation 48.44 |
Secondary
Proportion of Responders Achieving HbA1c <= 7.0%
Efficacy as measured in proportion of subjects achieving HbA1c \< or = to 7.0%
Time frame: Week 24
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Proportion of Responders Achieving HbA1c <= 7.0% | 18.3 percentage of participants |
| Technosphere Insulin-MedTone + Basal Insulin | Proportion of Responders Achieving HbA1c <= 7.0% | 21.7 percentage of participants |
| Insulin Aspart + Basal Insulin | Proportion of Responders Achieving HbA1c <= 7.0% | 30.7 percentage of participants |
p-value: 0.015895% CI: [0.23, 0.86]Regression, Logistic
Other Pre-specified
Incidence of Severe Hypoglycemia
Severe Hypoglycemia defined as: Requiring 3rd party assistance.
Time frame: Baseline to Week 24
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Incidence of Severe Hypoglycemia | 18.4 percentage of participants |
| Technosphere Insulin-MedTone + Basal Insulin | Incidence of Severe Hypoglycemia | 21.4 percentage of participants |
| Insulin Aspart + Basal Insulin | Incidence of Severe Hypoglycemia | 29.2 percentage of participants |
p-value: 0.015695% CI: [0.3198, 0.8877]Regression, Logistic
Other Pre-specified
Incidence of Total Hypoglycemia
Hypoglycemia, defined as blood glucose \<= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.
Time frame: Baseline to Week 24
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Incidence of Total Hypoglycemia | 96.0 percentage of participants |
| Technosphere Insulin-MedTone + Basal Insulin | Incidence of Total Hypoglycemia | 96.0 percentage of participants |
| Insulin Aspart + Basal Insulin | Incidence of Total Hypoglycemia | 99.4 percentage of participants |
Other Pre-specified
Severe Hypoglycemia Event Rate
Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)
Time frame: Baseline to Week 24
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Severe Hypoglycemia Event Rate | 8.05 Events/Subject-Month |
| Technosphere Insulin-MedTone + Basal Insulin | Severe Hypoglycemia Event Rate | 9.99 Events/Subject-Month |
| Insulin Aspart + Basal Insulin | Severe Hypoglycemia Event Rate | 14.45 Events/Subject-Month |
p-value: 0.1022Negative Binomial Regression
Other Pre-specified
Total Hypoglycemia Event Rate
Number of Hypoglycemic Events/Total Subject Exposure Time (in months)
Time frame: Baseline to Week 24
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Technosphere Insulin-Gen2 + Basal Insulin | Total Hypoglycemia Event Rate | 9.80 Events/Subject-Month |
| Technosphere Insulin-MedTone + Basal Insulin | Total Hypoglycemia Event Rate | 10.30 Events/Subject-Month |
| Insulin Aspart + Basal Insulin | Total Hypoglycemia Event Rate | 13.97 Events/Subject-Month |
p-value: <0.0001Negative Binomial Regression