Asthma, Moderate Chronic Obstructive Pulmonary Disease, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Conditions
Brief summary
Examine the effects of TI in combination with an anti-diabetic regimen including inhaled insulin versus anti-diabetic treatment without inhaled insulin on lung function & pulmonary safety
Interventions
Technosphere® Insulin delivered with Gen 2 inhaler with doses individualized for each participant in combination with an antidiabetic regimen of insulin and/or oral antidiabetic agents
DRUGUsual Care
Type 1 diabetics: long-acting (basal) insulin plus rapid-acting insulin, or pre-mix insulin Type 2 diabetics: oral anti-diabetic medications with or without long-acting (basal) 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
Asthma * Physician diagnosis of asthma with history of any or all of the following: recurrent wheezing, recurrent chest tightness, recurrent difficulty breathing, or cough, particularly worse at nighttime * Never smoked or former smokers (= 6 months since cessation) * ≥18 years of age * Prebronchodilator Forced Expiratory Volume in 1sec (FEV1) ≥ 60% Third National Health and Nutrition Examination Survey (NHANES III) predicted, prebronchodilator total lung capacity (TLC) ≥ 80% predicted Intermountain Thoracic Society (ITS), and prebronchodilator single breath carbon monoxide diffusing capacity of the lung (DLco) (unc) ≥70% predicted (Miller) * \< 30% day-to-day variability in daily morning Peak expiratory Volume (PEF) during the 2-week run-in period * Significant improvement in pre- to postbronchodilator spirometry (defined as an increase from baseline of ≥ 12% and ≥ 200 mL in FEV1 or Forced Vital Capacity \[FVC\]) at Screening/Visit 1 or documented significant improvement in pre- to postbronchodilator spirometry (as defined above) within past 12 months in subject's medical records or a documented positive methacholine challenge test within the past 12 months COPD * Physician diagnosis of COPD (including emphysema and/or chronic bronchitis), history of dyspnea and/or intermittent or daily chronic cough with or without sputum production, not attributable to any other known cause * Former smoker (≥ 6 months since cessation) with smoking history of ≥ 10 pack years * ≥40 years of age * Postbronchodilator FEV1/FVC ratio \< 70% * Postbronchodilator FEV1 ≥ 50% NHANES III predicted, total lung capacity (TLC) ≥ 80% predicted ITS, and DLco (unc) ≥ 50% predicted (Miller) Both * Clinical diagnosis of Type1 or 2 diabetes mellitus for ≥ 12 months and no change in anti-diabetic regiment for at least 90-days prior to screening * BMI of, \< 39 kg/m2 * Urine cotinine level ≤ 100ng/dL * Clinical diagnosis of obstructive lung disease * HbA1C \> 6.5% ≤ 11.5%
Exclusion criteria
* History of pulmonary exacerbation within 8 weeks of screening/V1 or between V1 and V2 * Use of systemic corticosteroids or antibiotics for respiratory illness within 8 weeks of screening/V1 OR between V1 and V2 * Increase from baseline in the use of short-acting bronchodilator or short-acting anticholinergic agents, or the combination of the 2, by ≥6 puffs or ≥3 nebulizer treatments per day for ≥ 2 days * Treatment with supplemental oxygen therapy, room air oxygen saturation, 94% or history of intubation or ICU admission for respiratory illness in the past 5 yrs. * Greater than 2 hospitalizations or ER or urgent care visits or required \>3 courses of systemic steroid in the past 12 months for respiratory illness * Use of Symlin® (pramlintide acetate) within the preceding 90 days * Two or more severe hypoglycemic episodes within 6 months of screening or episode of severe hypoglycemia between Screening and Baseline * Previous exposure to any inhaled insulin product * Currently using an insulin delivery pump * Requires significant change (define as initiation of a new medication or change in the dose or frequency of the controller medications) in the asthma or COPD therapeutic regimen within 8 weeks of Screening/Visit 1 (Week -4) or between Visit 1 and Baseline/Visit 2 * Severe complications of diabetes mellitus, in the opinion of the PI or sub-investigator, including symptomatic autonomic neuropathy; disabling peripheral neuropathy; active proliferative retinopathy; nephropathy with renal failure, renal transplant and/or dialysis; history of foot ulcers; nontraumatic amputations due to gangrene; and/or vascular claudication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Post-bronchodilator FEV1 From Baseline to Week 52 | 52 Weeks | Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) is measured at the pulmonary function laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Asthma Exacerbation by Treatment Arm | Baseline to Week 52 | Number of participants who experienced worsening of asthma symptoms |
| Number of Participants With COPD Exacerbation by Treatment Arm | Baseline to Week 52 | Number of participants who experienced worsening of COPD symptoms |
| Change in HbA1C From Baseline to Week 52 | Baseline, week 52 | — |
Countries
Russia, Ukraine, United States
Participant flow
Recruitment details
A total of 517 participants were screened in 5 countries . First participant was screened in March 2009.
Pre-assignment details
2 week screening period followed by a 2 week run-in period. After the screening period, 51 participants were randomized and 34 participants met eligibility criteria after the 2 week run-in period and were treated . Study was terminated based on data safety monitoring board recommendations.
Participants by arm
| Arm | Count |
|---|---|
| Technosphere® Insulin (Asthma) Technosphere® Insulin Inhalation Powder in combination with an antidiabetic regimen in diabetic patients with Asthma | 9 |
| Usual Care (Asthma) Usual and anti diabetic care in diabetic participants with Asthma. | 8 |
| Technosphere® Insulin (COPD) Technosphere® Insulin Inhalation Powder in combination with an antidiabetic regimen in diabetic patients with COPD | 9 |
| Usual Care (COPD) Usual and anti diabetic care in diabetic participants with COPD. | 8 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 2 | 0 |
| Overall Study | Study Terminated by Sponsor | 7 | 6 | 4 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Technosphere® Insulin (Asthma) | Usual Care (Asthma) | Technosphere® Insulin (COPD) | Usual Care (COPD) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.00 years STANDARD_DEVIATION 7.26 | 49.75 years STANDARD_DEVIATION 15.73 | 67.44 years STANDARD_DEVIATION 8.38 | 68.88 years STANDARD_DEVIATION 8.2 | 64.03 years STANDARD_DEVIATION 12.71 |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 2 Participants | 1 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants | 7 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 9 | 7 / 8 | 4 / 9 | 6 / 8 |
| serious Total, serious adverse events | 2 / 9 | 0 / 8 | 0 / 9 | 0 / 8 |
Outcome results
Primary
Change in Post-bronchodilator FEV1 From Baseline to Week 52
Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) is measured at the pulmonary function laboratory.
Time frame: 52 Weeks
Population: Only two participants completed both time points (one in the Usual Care (Asthma) Arm and one in the Usual Care (COPD) Arm); data are not provided due to privacy concerns.
Secondary
Change in HbA1C From Baseline to Week 52
Time frame: Baseline, week 52
Population: Only two participants completed both time points (one in the Usual Care (Asthma) Arm and one in the Usual Care (COPD) Arm); data are not provided due to privacy concerns
Secondary
Number of Participants With Asthma Exacerbation by Treatment Arm
Number of participants who experienced worsening of asthma symptoms
Time frame: Baseline to Week 52
Population: Safety population: Participants who received at least one dose of study medication. The outcome applies only to participants with underlying Asthma
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Technosphere® Insulin (Asthma) | Number of Participants With Asthma Exacerbation by Treatment Arm | Exacerbation of Asthma | 1 participants |
| Technosphere® Insulin (Asthma) | Number of Participants With Asthma Exacerbation by Treatment Arm | No Exacerbation of Asthma | 8 participants |
| Usual Care (Asthma) | Number of Participants With Asthma Exacerbation by Treatment Arm | Exacerbation of Asthma | 1 participants |
| Usual Care (Asthma) | Number of Participants With Asthma Exacerbation by Treatment Arm | No Exacerbation of Asthma | 7 participants |
Secondary
Number of Participants With COPD Exacerbation by Treatment Arm
Number of participants who experienced worsening of COPD symptoms
Time frame: Baseline to Week 52
Population: Safety population: Participants who received at least one dose of study medication. The outcome applies only to participants with underlying COPD
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Technosphere® Insulin (COPD) | Number of Participants With COPD Exacerbation by Treatment Arm | COPD Exacerbation | 3 participants |
| Technosphere® Insulin (COPD) | Number of Participants With COPD Exacerbation by Treatment Arm | No Exacerbation | 6 participants |
| Usual Care (COPD) | Number of Participants With COPD Exacerbation by Treatment Arm | COPD Exacerbation | 1 participants |
| Usual Care (COPD) | Number of Participants With COPD Exacerbation by Treatment Arm | No Exacerbation | 7 participants |