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

Type 1 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01445951
• Other study ID #: MKC-TI-171
• Status: Completed
• Phase: Phase 3
• First received: September 30, 2011
• Last updated: October 20, 2014
• Start date: September 2011
• Est. completion date: June 2013

Study information

• Verified date: October 2014
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 518
• Est. completion date: June 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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'

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Technosphere® Insulin with MedTone C Inhaler
Inhalation Powder and injectable insulin
• Technosphere ®Insulin with Gen2 Inhaler
Inhalation Powder and injectable insulin
• Insulin Aspart in combination with a basal insulin
Injectable insulin

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Mannkind Corporation

Countries where clinical trial is conducted

United States,  Brazil,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of Total Hypoglycemia	Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.	Baseline to Week 24	Yes
Other	Incidence of Severe Hypoglycemia	Severe Hypoglycemia defined as: Requiring 3rd party assistance.	Baseline to Week 24	Yes
Other	Total Hypoglycemia Event Rate	Number of Hypoglycemic Events/Total Subject Exposure Time (in months)	Baseline to Week 24	Yes
Other	Severe Hypoglycemia Event Rate	Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)	Baseline to Week 24	Yes
Primary	Change From Baseline to Week 24 in HbA1c	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	Baseline to Week 24	No
Secondary	FEV1 Change From Baseline to Week 24	Forced Expiratory Volume in 1 second - change from baseline to week 24	Baseline to Week 24	Yes
Secondary	FPG Change From Baseline to Week 24	Comparison of mean change from Baseline to Week 24 visit in fasting plasma glucose (FPG) levels (central laboratory results)	Baseline to Week 24	No
Secondary	Mean 7-point Glucose Baseline Values	Mean 7-point glucose at baseline	Baseline	No
Secondary	Mean 7-point Glucose Week 24 Values		Week 24	No
Secondary	Change in Body Weight From Baseline to Week 24	Change in body weight from Baseline to Week 24	Baseline to Week 24	No
Secondary	Proportion of Responders Achieving HbA1c <= 7.0%	Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%	Week 24	No