Type 2 Diabetes Mellitus
Conditions
Brief summary
Safety Follow-Up Trial to PDC-INS-0008 and MKC-TI-005
Detailed description
This is an uncontrolled study without comparator. Subjects were followed up to 4 years on Technosphere Insulin. Of 229 subjects 199 were exposed for ≥12 mo, 175 for ≥ 24 mo, 60 for ≥ 36 mo, 31 for ≥ 42 mo, & 2 for 48 mo.
Interventions
DRUGTechnosphere® Insulin Inhalation Powder and MedTone™ Inhaler
Inhalation starting at 15, 30, or 60U doses and can be titrated up or down by 15U to a minimum of 15U or a maximum of 90U
Sponsors
Mannkind Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Previous completion of PDC-INS-0008 or MKC-TI-005 * Subjects must be able to attend all scheduled visits and, in the opinion of the Investigator, be able to complete this safety trial * Subjects must be able to understand English or have access to validated primary language trial documents * Written informed consent
Exclusion criteria
* Drug or alcohol dependency * Smokers (subjects are expected to remain non-smokers throughout their participation in this trial) * Known hypersensitivity to the trial drug or to drugs of similar chemical structures * Anemia (hemoglobin level \< 11 g/dL for females or \< 12 g/dL for males) * Evidence of moderate or greater ketones in urine * Women of childbearing potential practicing inadequate birth control. (Adequate birth control is defined as using oral contraceptives, condoms or diaphragms with spermicide, intrauterine devices, Depo-Provera, contraceptive patches or surgical sterilization) * Women who are pregnant * Clinically significant adverse events that remain unresolved from the previous trial and/or clinically significant abnormal laboratory values which are determined by the Investigator or the MKC Medical Monitor to be unsafe or confounding to continued participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annual Rate of Change in FEV1 From Baseline to End of Study | Baseline to 48 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Change in DLCo From Baseline to End of Study | Baseline to 48 months | — |
| Change in HbA1c From Baseline to Last Measurement on Study Drug (Maximum of 48 Months) | Baseline to last measurement on study drug (maximum of 48 months | Change in HbA1c from Baseline to last measurement on study drug (maximum of 48 months) |
| Annual Rate of Change in FVC From Baseline to End of Study | Baseline to 48 months | — |
| Change in Weight in kg From Baseline to End of Study | Baseline to last measurement on study drug (maximum of 48 months) | Baseline to last measurement on study drug (maximum of 48 months) |
| High Resolution Computerized Tomography Scans of the Chest | End of study | — |
| Change in FPG From Baseline to Last Study Measurement on Treatment (Maximum of 48 Months) | Baseline to last study measurement on treatment (maximum of 48 months) | Change from Baseline to last study measurement on treatment (maximum of 48 months) |
Countries
Bulgaria, Czechia, Germany, United States
Participant flow
Recruitment details
First patient enrolled May 31, 2004 Multi-center international trial conducted in USA, Bulgaria, Czech Republic, and Germany. Conducted in medical offices, hospital clinics, and universities.
Pre-assignment details
This was a follow-on trial for subjects who completed one of the two parent trials (PDC-IND-0008 or MKC-TI-005). Inclusion/Exclusion was participation in these parent trials.
Participants by arm
| Arm | Count |
|---|---|
| TI Inhalation Powder Technosphere® Insulin Inhalation Powder | 229 |
| Total | 229 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 16 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Physician Decision | 8 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Various | 12 |
| Overall Study | Withdrawal by Subject | 28 |
Baseline characteristics
| Characteristic | TI Inhalation Powder |
|---|---|
| Age, Continuous | 56.4 years |
| DLCo | 26.16 mL/min/mmHg STANDARD_DEVIATION 6.21 |
| FEV1 | 2.99 Liters STANDARD_DEVIATION 0.7 |
| FPG | 167.7 mg/dL STANDARD_DEVIATION 42.1 |
| FVC | 3.85 Liters STANDARD_DEVIATION 0.89 |
| HbA1c | 7.97 % STANDARD_DEVIATION 1.2 |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 136 Participants |
| Weight | 87.2 kg STANDARD_DEVIATION 15.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 156 / 229 |
| serious Total, serious adverse events | 30 / 229 |
Outcome results
Primary
Annual Rate of Change in FEV1 From Baseline to End of Study
Time frame: Baseline to 48 months
Population: Safety Population defined as all subjects who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TI Inhalation Powder | Annual Rate of Change in FEV1 From Baseline to End of Study | -0.048 Liters per year | Standard Error 0.006 |
Comparison: A random coefficient model with a random intercept and slope associated with each subject, was fitted (using the PROC MIXED procedure in SAS) to the observed FEV1 data to estimate the annual rate of decline. The model included terms for baseline FEV1 and time (in years) of FEV1 measurements. Missing pulmonary functions were not imputed.95% CI: [-0.059, -0.037]Random coefficient
Secondary
Annual Rate of Change in DLCo From Baseline to End of Study
Time frame: Baseline to 48 months
Population: Safety
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TI Inhalation Powder | Annual Rate of Change in DLCo From Baseline to End of Study | -0.311 mL/min/mmHg per year | Standard Error 0.073 |
Comparison: A random coefficient model with a random intercept and slope associated with each subject, was fitted (using the PROC MIXED procedure in SAS) to the observed DLco data to estimate the annual rate of decline. The model included terms for baseline DLco and time (in years) of DLco measurements. Missing pulmonary functions were not imputed.95% CI: [-0.454, -0.168]Random Coefficient
Secondary
Annual Rate of Change in FVC From Baseline to End of Study
Time frame: Baseline to 48 months
Population: Safety
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TI Inhalation Powder | Annual Rate of Change in FVC From Baseline to End of Study | -0.058 Liters per year | Standard Error 0.007 |
Comparison: A random coefficient model with a random intercept and slope associated with each subject, was fitted (using the PROC MIXED procedure in SAS) to the observed FVC data to estimate the annual rate of decline. The model included terms for baseline FVC and time (in years) of FVC measurements. Missing pulmonary functions were not imputed.95% CI: [-0.072, -0.043]Random Coefficient
Secondary
Change in FPG From Baseline to Last Study Measurement on Treatment (Maximum of 48 Months)
Change from Baseline to last study measurement on treatment (maximum of 48 months)
Time frame: Baseline to last study measurement on treatment (maximum of 48 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TI Inhalation Powder | Change in FPG From Baseline to Last Study Measurement on Treatment (Maximum of 48 Months) | -5.34 milligrams per deciliter | Standard Deviation 51.43 |
Secondary
Change in HbA1c From Baseline to Last Measurement on Study Drug (Maximum of 48 Months)
Change in HbA1c from Baseline to last measurement on study drug (maximum of 48 months)
Time frame: Baseline to last measurement on study drug (maximum of 48 months
Population: Safety
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TI Inhalation Powder | Change in HbA1c From Baseline to Last Measurement on Study Drug (Maximum of 48 Months) | 0.20 percentage | Standard Deviation 1.2 |
Secondary
Change in Weight in kg From Baseline to End of Study
Baseline to last measurement on study drug (maximum of 48 months)
Time frame: Baseline to last measurement on study drug (maximum of 48 months)
Population: Safety
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TI Inhalation Powder | Change in Weight in kg From Baseline to End of Study | 1.42 kilograms | Standard Deviation 4.41 |
Secondary
High Resolution Computerized Tomography Scans of the Chest
Time frame: End of study
Population: participants in Safety population with available post-baseline data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TI Inhalation Powder | High Resolution Computerized Tomography Scans of the Chest | Normal HRCT subjects | 47 participants |
| TI Inhalation Powder | High Resolution Computerized Tomography Scans of the Chest | Abnormal, clinically not significant subjects | 147 participants |
| TI Inhalation Powder | High Resolution Computerized Tomography Scans of the Chest | Abnormal, Clinically Significant HRCT subjects | 12 participants |