Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period

Tracking Information
First Submitted Date ICMJE	September 30, 2011
First Posted Date ICMJE	October 4, 2011
Results First Submitted Date	July 22, 2014
Results First Posted Date	October 22, 2014
Last Update Posted Date	October 22, 2014
Study Start Date ICMJE	September 2011
Actual Primary Completion Date	May 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 20, 2014)	Change From Baseline to Week 24 in HbA1c [ Time Frame: 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
Original Primary Outcome Measures ICMJE; (submitted: October 3, 2011)	Effect of treatment as measured by change in glycated hemoglobin (HbA1c): Comparison of baseline HbA1c to end of treatment HbA1c after 24 weeks [ Time Frame: 24 Weeks ]; Change in HbA1c baseline
Change History	Complete list of historical versions of study NCT01445951 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 20, 2014)	FEV1 Change From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]Forced Expiratory Volume in 1 second - change from baseline to week 24; FPG Change From Baseline to Week 24 [ Time Frame: 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 [ Time Frame: Baseline ]Mean 7-point glucose at baseline; Mean 7-point Glucose Week 24 Values [ Time Frame: Week 24 ]; Change in Body Weight From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]Change in body weight from Baseline to Week 24; Proportion of Responders Achieving HbA1c <= 7.0% [ Time Frame: Week 24 ]Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%
Original Secondary Outcome Measures ICMJE; (submitted: October 3, 2011)	FEV1 changes from Baseline to the final treatment visit compared between TI-Gen2C and TI-MedTone C treatment groups [ Time Frame: 24 Weeks ]Change in FEV1 baseline; Comparison of mean change from randomization visit to Week 24 visit in fasting plasma glucose (FPG) levels (central laboratory results) [ Time Frame: 24 Weeks ]Change in FPG baseline; Comparison of mean 7-point glucose from the week before the randomization visit to those measured the week before the Week 24 visit [ Time Frame: 24 Weeks ]Change in FEV1 baseline; Change in body weight from Randomization to the end of the treatment period [ Time Frame: 24 Weeks ]Change in body weight baseline
Current Other Outcome Measures ICMJE; (submitted: October 20, 2014)	Incidence of Total Hypoglycemia [ Time Frame: 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 [ Time Frame: Baseline to Week 24 ]Severe Hypoglycemia defined as: Requiring 3rd party assistance.; Total Hypoglycemia Event Rate [ Time Frame: Baseline to Week 24 ]Number of Hypoglycemic Events/Total Subject Exposure Time (in months); Severe Hypoglycemia Event Rate [ Time Frame: Baseline to Week 24 ]Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period
Official Title ICMJE	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Type 1 Diabetes Mellitus
Intervention ICMJE	Drug: Technosphere® Insulin with MedTone C Inhaler Inhalation Powder and injectable insulin; Drug: Technosphere ®Insulin with Gen2 Inhaler Inhalation Powder and injectable insulin; Drug: Insulin Aspart in combination with a basal insulin Injectable insulin
Study Arms	Experimental: Technosphere® Insulin with MedTone C Inhaler Subjects will receive TI with the MedToneC inhaler and remain on the basal insulin they were taking prior to study entry Intervention: Drug: Technosphere® Insulin with MedTone C Inhaler; Active Comparator: Aspart Group Subjects will receive insulin aspart and remain on the basal insulin they were taking prior to study entry Intervention: Drug: Insulin Aspart in combination with a basal insulin; Experimental: Technosphere ® Insulin-Gen2 Group Subject will receive Technosphere Insulin with Gen2 Inhaler and remain on the basal insulin they were taking prior to study entry Intervention: Drug: Technosphere ®Insulin with Gen2 Inhaler
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: August 19, 2013)	518
Original Estimated Enrollment ICMJE; (submitted: October 3, 2011)	471
Actual Study Completion Date	June 2013
Actual Primary Completion Date	May 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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'
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Brazil, Russian Federation, Ukraine, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01445951
Other Study ID Numbers ICMJE	MKC-TI-171
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Mannkind Corporation
Study Sponsor ICMJE	Mannkind Corporation
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Mannkind Corporation
Verification Date	October 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP