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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Mannkind Corporation

ClinicalTrials.gov Identifier:

NCT01445951

First received: September 30, 2011

Last updated: October 20, 2014

Last verified: October 2014

History of Changes

Tracking Information
First Received Date ^ICMJE	September 30, 2011
Last Updated Date	October 20, 2014
Start Date ^ICMJE	September 2011
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 ] [ Designated as safety issue: No ] 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 ] [ Designated as safety issue: No ] 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 ] [ Designated as safety issue: Yes ] 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 ] [ Designated as safety issue: No ] 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 ] [ Designated as safety issue: No ] Mean 7-point glucose at baseline Mean 7-point Glucose Week 24 Values [ Time Frame: Week 24 ] [ Designated as safety issue: No ] Change in Body Weight From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ] Change in body weight from Baseline to Week 24 Proportion of Responders Achieving HbA1c <= 7.0% [ Time Frame: Week 24 ] [ Designated as safety issue: No ] 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 ] [ Designated as safety issue: Yes ] 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 ] [ Designated as safety issue: No ] 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 ] [ Designated as safety issue: No ] Change in FEV1 baseline Change in body weight from Randomization to the end of the treatment period [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ] Change in body weight baseline
Current Other Outcome Measures ^ICMJE (submitted: October 20, 2014)	Incidence of Total Hypoglycemia [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ] 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 ] [ Designated as safety issue: Yes ] Severe Hypoglycemia defined as: Requiring 3rd party assistance. Total Hypoglycemia Event Rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ] Number of Hypoglycemic Events/Total Subject Exposure Time (in months) Severe Hypoglycemia Event Rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ] 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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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 Arm (s)	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 *	Not Provided
* 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
Enrollment ^ICMJE	518
Completion Date	June 2013
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'
Gender	Both
Ages	18 Years and older
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ^ICMJE	United States, Brazil, Russian Federation, Ukraine
Removed Location Countries

Administrative Information
NCT Number ^ICMJE	NCT01445951
Other Study ID Numbers ^ICMJE	MKC-TI-171
Has Data Monitoring Committee	Yes
Responsible Party	Mannkind Corporation
Study Sponsor ^ICMJE	Mannkind Corporation
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	Mannkind Corporation
Verification Date	October 2014
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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