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

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

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

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Technosphere® Insulin with MedTone C Inhaler; Drug: Insulin Aspart in combination with a basal insulin; Drug: Technosphere ®Insulin with Gen2 Inhaler

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: Interventional
• Enrollment (Actual): 518
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-170
  • SP
    • Sao Paulo, SP, Brazil, 01244-030
• Russian Federation
  • RUS
    • Kemerovo, RUS, Russian Federation, 650066
    • Moscow, RUS, Russian Federation, 105120
    • Moscow, RUS, Russian Federation, 109240
    • Moscow, RUS, Russian Federation, 117036
    • Moscow, RUS, Russian Federation, 117593
    • Moscow, RUS, Russian Federation, 119048
    • Moscow, RUS, Russian Federation, 119435
    • Moscow, RUS, Russian Federation, 125299
    • Moscow, RUS, Russian Federation, 125315
    • Petrozavodsk, RUS, Russian Federation, 185019
    • Smolensk, RUS, Russian Federation, 214018
    • St Petersburg, RUS, Russian Federation, 194291
    • St Petersburg, RUS, Russian Federation, 195257
    • St Petersburg, RUS, Russian Federation, 198013
    • St. Petersburg, RUS, Russian Federation, 192148
    • St. Petersburg, RUS, Russian Federation, 194044
    • St. Petersburg, RUS, Russian Federation, 194354
    • Yaroslavl, RUS, Russian Federation, 150003
    • Yaroslavl, RUS, Russian Federation, 150062
  • Russia
    • St. Petersburg, Russia, Russian Federation, 191186
    • St. Petersburg, Russia, Russian Federation, 193312
• Ukraine
  • UKR
    • Dnipropetrovsk, UKR, Ukraine, 49023
    • Donetsk, UKR, Ukraine, 83114
    • Kharkiv, UKR, Ukraine, 61070
    • Kiev, UKR, Ukraine, 04053
    • Kiev, UKR, Ukraine, 04114
    • Kyiv, UKR, Ukraine, 02175
    • Odesa, UKR, Ukraine, 65039
    • Odesa, UKR, Ukraine, 65114
    • Vinnytsya, UKR, Ukraine, 21010
• United States
  • California
    • Burlingame, California, United States, 94010
    • Escondido, California, United States, 92026
    • Huntington Beach, California, United States, 92648
    • La Jolla, California, United States, 92037
    • La Mesa, California, United States, 91942
    • Long Beach, California, United States, 90806
    • Los Angeles, California, United States, 90036
    • Los Angeles, California, United States, 90017
    • Los Gatos, California, United States, 95032
    • San Mateo, California, United States, 94401
    • Santa Barbara, California, United States, 93105
    • Tustin, California, United States, 92780
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Florida
    • Hialeah, Florida, United States, 33012
    • Hollywood, Florida, United States, 33021
    • Miami, Florida, United States, 33173
    • Miami, Florida, United States, 33156
    • New Port Richey, Florida, United States, 34652
    • Palm Harbor, Florida, United States, 34652
    • West Palm Beach, Florida, United States, 33401
  • Georgia
    • Atlanta, Georgia, United States, 30308
    • Atlanta, Georgia, United States, 30318
    • Dunwoody, Georgia, United States, 30338
    • Lawrenceville, Georgia, United States, 30045
    • Roswell, Georgia, United States, 30076
  • Illinois
    • Chicago, Illinois, United States, 60602
  • Indiana
    • Vincennes, Indiana, United States, 47591
  • Iowa
    • Des Moines, Iowa, United States, 50314
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
    • Metairie, Louisiana, United States, 70006
    • New Orleans, Louisiana, United States, 70112
  • Minnesota
    • Edina, Minnesota, United States, 55435
  • Missouri
    • Jefferson City, Missouri, United States, 65109
    • St Peters, Missouri, United States, 63376
    • St. Louis, Missouri, United States, 63110
  • Montana
    • Billings, Montana, United States, 59101
  • Nebraska
    • Omaha, Nebraska, United States, 68114
    • Omaha, Nebraska, United States, 68131
  • New Jersey
    • Paramus, New Jersey, United States, 07652
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
  • New York
    • Flushing, New York, United States, 11365
    • New Hyde Park, New York, United States, 11042
    • New York, New York, United States, 10016
  • North Carolina
    • Asheville, North Carolina, United States, 28803
    • Greenville, North Carolina, United States, 27834
    • Morehead City, North Carolina, United States, 28557
  • Oregon
    • Portland, Oregon, United States, 97239
  • South Carolina
    • Greer, South Carolina, United States, 29651
  • Tennessee
    • Bartlett, Tennessee, United States, 38133
  • Texas
    • Arlington, Texas, United States, 76014
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75230
    • Houston, Texas, United States, 77095
    • San Antonio, Texas, United States, 78229
  • Utah
    • Murray, Utah, United States, 84123
  • Washington
    • Federal Way, Washington, United States, 98003
    • Renton, Washington, United States, 98057
    • Wenatchee, Washington, United States, 98801

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Technosphere® Insulin with MedTone C Inhaler; Inhalation Powder and injectable insulin
Active Comparator: Aspart Group; Subjects will receive insulin aspart and remain on the basal insulin they were taking prior to study entry	Drug: Insulin Aspart in combination with a basal insulin; Injectable 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	Drug: Technosphere ®Insulin with Gen2 Inhaler; Inhalation Powder and injectable insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 Change From Baseline to Week 24	Forced Expiratory Volume in 1 second - change from baseline to week 24	Baseline to Week 24
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
Mean 7-point Glucose Baseline Values	Mean 7-point glucose at baseline	Baseline
Mean 7-point Glucose Week 24 Values		Week 24
Change in Body Weight From Baseline to Week 24	Change in body weight from Baseline to Week 24	Baseline to Week 24
Proportion of Responders Achieving HbA1c <= 7.0%	Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%	Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Incidence of Severe Hypoglycemia	Severe Hypoglycemia defined as: Requiring 3rd party assistance.	Baseline to Week 24
Total Hypoglycemia Event Rate	Number of Hypoglycemic Events/Total Subject Exposure Time (in months)	Baseline to Week 24
Severe Hypoglycemia Event Rate	Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Mannkind Corporation

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: October 3, 2011
• First Posted (Estimate): October 4, 2011

Study Record Updates

• Last Update Posted (Estimate): October 22, 2014
• Last Update Submitted That Met QC Criteria: October 20, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart
• Other Study ID Numbers: MKC-TI-171