Clinical trial NCT01445951: Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period
Official title: A Phase 3, Multicenter, Open-label, Randomized, Forced-titration Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Insulin Inhalation Powder in Combination With a Basal Insulin Versus Insulin Aspart in Combination With a Basal Insulin in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2011-10-04
Enrollment: 518
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: 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.

Eligibility criteria: 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'

Primary outcomes:
measure: Change From Baseline to Week 24 in HbA1c
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: FEV1 Change From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: FPG Change From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Mean 7-point Glucose Baseline Values
timeFrame: Baseline
measure: Mean 7-point Glucose Week 24 Values
timeFrame: Week 24
measure: Change in Body Weight From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Proportion of Responders Achieving HbA1c <= 7.0%
timeFrame: Week 24
Other outcomes:
measure: Incidence of Total Hypoglycemia
timeFrame: Baseline to Week 24
measure: Incidence of Severe Hypoglycemia
timeFrame: Baseline to Week 24
measure: Total Hypoglycemia Event Rate
timeFrame: Baseline to Week 24
measure: Severe Hypoglycemia Event Rate
timeFrame: Baseline to Week 24
Locations:
city: Burlingame
country: United States
state: California
city: Escondido
country: United States
state: California
city: Huntington Beach
country: United States
state: California
city: La Jolla
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Gatos
country: United States
state: California
city: San Mateo
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Tustin
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Hialeah
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Dunwoody
country: United States
state: Georgia
city: Lawrenceville
country: United States
state: Georgia
city: Roswell
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Vincennes
country: United States
state: Indiana
city: Des Moines
country: United States
state: Iowa
city: Baton Rouge
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Edina
country: United States
state: Minnesota
city: Jefferson City
country: United States
state: Missouri
city: St Peters
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Omaha
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Paramus
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Flushing
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Morehead City
country: United States
state: North Carolina
city: Portland
country: United States
state: Oregon
city: Greer
country: United States
state: South Carolina
city: Bartlett
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Murray
country: United States
state: Utah
city: Federal Way
country: United States
state: Washington
city: Renton
country: United States
state: Washington
city: Wenatchee
country: United States
state: Washington
city: Porto Alegre
country: Brazil
state: RS
city: Sao Paulo
country: Brazil
state: SP
city: St. Petersburg
country: Russian Federation
state: Russia
city: St. Petersburg
country: Russian Federation
state: Russia
city: Kemerovo
country: Russian Federation
state: RUS
city: Moscow
country: Russian Federation
state: RUS
city: Moscow
country: Russian Federation
state: RUS
city: Moscow
country: Russian Federation
state: RUS
city: Moscow
country: Russian Federation
state: RUS
city: Moscow
country: Russian Federation
state: RUS
city: Moscow
country: Russian Federation
state: RUS
city: Moscow
country: Russian Federation
state: RUS
city: Moscow
country: Russian Federation
state: RUS
city: Petrozavodsk
country: Russian Federation
state: RUS
city: Smolensk
country: Russian Federation
state: RUS
city: St Petersburg
country: Russian Federation
state: RUS
city: St Petersburg
country: Russian Federation
state: RUS
city: St Petersburg
country: Russian Federation
state: RUS
city: St. Petersburg
country: Russian Federation
state: RUS
city: St. Petersburg
country: Russian Federation
state: RUS
city: St. Petersburg
country: Russian Federation
state: RUS
city: Yaroslavl
country: Russian Federation
state: RUS
city: Yaroslavl
country: Russian Federation
state: RUS
city: Dnipropetrovsk
country: Ukraine
state: UKR
city: Donetsk
country: Ukraine
state: UKR
city: Kharkiv
country: Ukraine
state: UKR
city: Kiev
country: Ukraine
state: UKR
city: Kiev
country: Ukraine
state: UKR
city: Kyiv
country: Ukraine
state: UKR
city: Odesa
country: Ukraine
state: UKR
city: Odesa
country: Ukraine
state: UKR
city: Vinnytsya
country: Ukraine
state: UKR
Study officials:
References:
citation: Seaquist ER, Blonde L, McGill JB, Heller SR, Kendall DM, Bumpass JB, Pompilio FM, Grant ML. Hypoglycaemia is reduced with use of inhaled Technosphere(R) Insulin relative to insulin aspart in type 1 diabetes mellitus. Diabet Med. 2020 May;37(5):752-759. doi: 10.1111/dme.14202. Epub 2019 Dec 19.
citation: Bode BW, McGill JB, Lorber DL, Gross JL, Chang PC, Bregman DB; Affinity 1 Study Group. Inhaled Technosphere Insulin Compared With Injected Prandial Insulin in Type 1 Diabetes: A Randomized 24-Week Trial. Diabetes Care. 2015 Dec;38(12):2266-73. doi: 10.2337/dc15-0075. Epub 2015 Jul 15.