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

NCT01445951 | Completed Phase 3 Results DMC

• 1 other identifier: MKC-TI-171
• Study Type: interventional
• Target: 518
• Locations: 4 countries
• Sites: 90

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

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• FEV1 Change From Baseline to Week 24

  Baseline to Week 24

• FPG Change From Baseline to Week 24

  Baseline to Week 24

• Mean 7-point Glucose Baseline Values

  Baseline

• Mean 7-point Glucose Week 24 Values

  Week 24

• Change in Body Weight From Baseline to Week 24

  Baseline to Week 24

Other Outcomes (4)

• Incidence of Total Hypoglycemia

  Baseline to Week 24

• Incidence of Severe Hypoglycemia

  Baseline to Week 24

• Total Hypoglycemia Event Rate

  Baseline to Week 24

Study Arms (3)

Technosphere® Insulin with MedTone C Inhaler

EXPERIMENTAL

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

Aspart Group

ACTIVE COMPARATOR

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

Technosphere ® Insulin-Gen2 Group

EXPERIMENTAL

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

Interventions

Technosphere® Insulin with MedTone C Inhaler DRUG

Inhalation Powder and injectable insulin

Technosphere® Insulin with MedTone C Inhaler

Technosphere ®Insulin with Gen2 Inhaler DRUG

Inhalation Powder and injectable insulin

Technosphere ® Insulin-Gen2 Group

Insulin Aspart in combination with a basal insulin DRUG

Injectable insulin

Aspart Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (90)

Unknown Facility

Burlingame, California, 94010, United States

Location

Unknown Facility

Escondido, California, 92026, United States

Location

Unknown Facility

Huntington Beach, California, 92648, United States

Location

Unknown Facility

La Jolla, California, 92037, United States

Location

Unknown Facility

La Mesa, California, 91942, United States

Location

Unknown Facility

Long Beach, California, 90806, United States

Location

Unknown Facility

Los Angeles, California, 90017, United States

Location

Unknown Facility

Los Angeles, California, 90036, United States

Location

Unknown Facility

Los Gatos, California, 95032, United States

Location

Unknown Facility

San Mateo, California, 94401, United States

Location

Unknown Facility

Santa Barbara, California, 93105, United States

Location

Unknown Facility

Tustin, California, 92780, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Hialeah, Florida, 33012, United States

Location

Unknown Facility

Hollywood, Florida, 33021, United States

Location

Unknown Facility

Miami, Florida, 33156, United States

Location

Unknown Facility

Miami, Florida, 33173, United States

Location

Unknown Facility

New Port Richey, Florida, 34652, United States

Location

Unknown Facility

Palm Harbor, Florida, 34652, United States

Location

Unknown Facility

West Palm Beach, Florida, 33401, United States

Location

Unknown Facility

Atlanta, Georgia, 30308, United States

Location

Unknown Facility

Atlanta, Georgia, 30318, United States

Location

Unknown Facility

Dunwoody, Georgia, 30338, United States

Location

Unknown Facility

Lawrenceville, Georgia, 30045, United States

Location

Unknown Facility

Roswell, Georgia, 30076, United States

Location

Unknown Facility

Chicago, Illinois, 60602, United States

Location

Unknown Facility

Vincennes, Indiana, 47591, United States

Location

Unknown Facility

Des Moines, Iowa, 50314, United States

Location

Unknown Facility

Baton Rouge, Louisiana, 70808, United States

Location

Unknown Facility

Metairie, Louisiana, 70006, United States

Location

Unknown Facility

New Orleans, Louisiana, 70112, United States

Location

Unknown Facility

Edina, Minnesota, 55435, United States

Location

Unknown Facility

City of Saint Peters, Missouri, 63376, United States

Location

Unknown Facility

Jefferson City, Missouri, 65109, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Billings, Montana, 59101, United States

Location

Unknown Facility

Omaha, Nebraska, 68114, United States

Location

Unknown Facility

Omaha, Nebraska, 68131, United States

Location

Unknown Facility

Paramus, New Jersey, 07652, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87131, United States

Location

Unknown Facility

Flushing, New York, 11365, United States

Location

Unknown Facility

New Hyde Park, New York, 11042, United States

Location

Unknown Facility

New York, New York, 10016, United States

Location

Unknown Facility

Asheville, North Carolina, 28803, United States

Location

Unknown Facility

Greenville, North Carolina, 27834, United States

Location

Unknown Facility

Morehead City, North Carolina, 28557, United States

Location

Unknown Facility

Portland, Oregon, 97239, United States

Location

Unknown Facility

Greer, South Carolina, 29651, United States

Location

Unknown Facility

Bartlett, Tennessee, 38133, United States

Location

Unknown Facility

Arlington, Texas, 76014, United States

Location

Unknown Facility

Dallas, Texas, 75230, United States

Location

Unknown Facility

Dallas, Texas, 75246, United States

Location

Unknown Facility

Houston, Texas, 77095, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

Murray, Utah, 84123, United States

Location

Unknown Facility

Federal Way, Washington, 98003, United States

Location

Unknown Facility

Renton, Washington, 98057, United States

Location

Unknown Facility

Wenatchee, Washington, 98801, United States

Location

Unknown Facility

Porto Alegre, Rio Grande do Sul, 90035-170, Brazil

Location

Unknown Facility

São Paulo, São Paulo, 01244-030, Brazil

Location

Unknown Facility

Saint Petersburg, Russia, 191186, Russia

Location

Unknown Facility

Saint Petersburg, Russia, 193312, Russia

Location

Unknown Facility

Kemerovo, RUS, 650066, Russia

Location

Unknown Facility

Moscow, RUS, 105120, Russia

Location

Unknown Facility

Moscow, RUS, 109240, Russia

Location

Unknown Facility

Moscow, RUS, 117036, Russia

Location

Unknown Facility

Moscow, RUS, 117593, Russia

Location

Unknown Facility

Moscow, RUS, 119048, Russia

Location

Unknown Facility

Moscow, RUS, 119435, Russia

Location

Unknown Facility

Moscow, RUS, 125299, Russia

Location

Unknown Facility

Moscow, RUS, 125315, Russia

Location

Unknown Facility

Petrozavodsk, RUS, 185019, Russia

Location

Unknown Facility

Saint Petersburg, RUS, 192148, Russia

Location

Unknown Facility

Saint Petersburg, RUS, 194044, Russia

Location

Unknown Facility

Saint Petersburg, RUS, 194291, Russia

Location

Unknown Facility

Saint Petersburg, RUS, 194354, Russia

Location

Unknown Facility

Saint Petersburg, RUS, 195257, Russia

Location

Unknown Facility

Saint Petersburg, RUS, 198013, Russia

Location

Unknown Facility

Smolensk, RUS, 214018, Russia

Location

Unknown Facility

Yaroslavl, RUS, 150003, Russia

Location

Unknown Facility

Yaroslavl, RUS, 150062, Russia

Location

Unknown Facility

Dnipropetrovsk, UKR, 49023, Ukraine

Location

Unknown Facility

Donetsk, UKR, 83114, Ukraine

Location

Unknown Facility

Kharkiv, UKR, 61070, Ukraine

Location

Unknown Facility

Kiev, UKR, 04053, Ukraine

Location

Unknown Facility

Kiev, UKR, 04114, Ukraine

Location

Unknown Facility

Kyiv, UKR, 02175, Ukraine

Location

Unknown Facility

Odesa, UKR, 65039, Ukraine

Location

Unknown Facility

Odesa, UKR, 65114, Ukraine

Location

Unknown Facility

Vinnytsia, UKR, 21010, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 31811662 DERIVED

• 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.

  PMID: 26180109 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Aspart

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: MannKind Corporation

aboss@mannkindcorp.com

201-983-5000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 4, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: June 1, 2013
• Last Updated: October 22, 2014
• Results First Posted: October 22, 2014

Record last verified: 2014-10

Locations

US (58); BR (2); UA (9); RU (21)