Clinical trial NCT00642616: Evaluate Safety of Technosphere® Insulin (TI) in Diabetic Subjects With Moderate Obstructive Pulmonary Disease
Official title: A Phase 3, Open-label, Randomized Clinical Trial to Evaluate the Safety of Technosphere® Insulin Inhalation Powder in Type 1 or Type 2 Diabetic Subjects With Obstructive Pulmonary Disease (Asthma or Chronic Obstructive Pulmonary Disease) Over a 12 Months Treatment Period With a 2 Month Follow-up
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Moderate Chronic Obstructive Pulmonary Disease
Asthma
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2008-03-25
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in Post-bronchodilator FEV1 From Baseline to Week 52
timeFrame: 52 Weeks
Secondary outcomes:
measure: Number of Participants With Asthma Exacerbation by Treatment Arm
timeFrame: Baseline to Week 52
measure: Number of Participants With COPD Exacerbation by Treatment Arm
timeFrame: Baseline to Week 52
measure: Change in HbA1C From Baseline to Week 52
timeFrame: Baseline, week 52
Other outcomes:
Locations:
city: Mission Hills
country: United States
state: California
city: San Diego
country: United States
state: California
city: Palm Harbor
country: United States
state: Florida
city: Flint
country: United States
state: Michigan
city: Morehead City
country: United States
state: North Carolina
city: Medford
country: United States
state: Oregon
city: Greenville
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Federal Way
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Yaroslavl
country: Russian Federation
state: RUS
city: Kemerovo
country: Russian Federation
state: RU
city: Moscow
country: Russian Federation
state: RU
city: St Petersburg
country: Russian Federation
state: RU
city: St. Petersburg
country: Russian Federation
state: RU
city: St. Petersburg
country: Russian Federation
state: RU
city: St. Petersburg
country: Russian Federation
state: RU
city: Kiev
country: Ukraine
state: UA
city: Kyiv
country: Ukraine
state: UA
Study officials:
affiliation: Mannkind Corporation
name: Chief Medical Officer
role: STUDY_CHAIR
References: