Safety and Efficacy of Technosphere® Insulin Inhalation Powder and Lantus® Compared to Humalog® and Lantus® Over 16-Weeks

NCT00700622 | Terminated Phase 3 Results

• 1 other identifier: MKC-TI-117
• Study Type: interventional
• Target: 130
• Locations: 2 countries
• Sites: 22

Brief Summary

The objective of this study is to demonstrate that TI® Inhalation Powder combined with Lantus® is as effective as Humalog® combined with Lantus® on HbA1c.

Conditions

Diabetes, Type 1

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in HbA1c to Week 16

  Change from Baseline in glycosylated hemoglobin at Week 16

  Baseline to Week 16

Study Arms (2)

TI + Insulin glargine

EXPERIMENTAL

Technosphere Insulin Inhalation Powder in combination with Lantus (insulin glargine)

Drug: Technosphere Insulin

Insulin lispro + Insulin glargine

EXPERIMENTAL

Humalog (insulin lispro) in combination with Lantus (insulin glargine)

Drug: Insulin glargine; Drug: Insulin lispro

Interventions

Technosphere Insulin DRUG

Technosphere Insulin Inhalation Powder 15U or 30U

TI + Insulin glargine

Insulin glargine DRUG

Lantus-injectible supplied as 3mL (300 units) pens

Insulin lispro + Insulin glargine

Insulin lispro DRUG

Humalog autopen cartridges pre-filled with 3mL (300 units)

Insulin lispro + Insulin glargine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ≥ 18 and ≤ 80 years old
• Clinical diagnosis of type 1 diabetes mellitus for more than 12 months
• Body mass index (BMI) ≤ 30 kg/m2
• Stable antidiabetic regimen of sc insulin therapy at a total daily dose ≤ 1.5 IU/kg/day
• HbA1c \> 7.0% and ≤ 9.0%
• C-peptide level ≤ 0.30 pmol/mL
• Nonsmokers (includes cigarettes, cigars, pipes, and chewing tobacco) for at least the preceding 6 months
• Negative urine cotinine defined as ≤ 100 ng/mL
• Pulmonary function tests (PFTs):
• Forced expiratory volume in 1 second (FEV1) ≥ 70% Third National Health and Nutrition Examination Survey (NHANES III) predicted
• FEV1 as a percentage of FEV1/forced vital capacity (FVC) ≥ 70% (NHANES III) predicted
• Total lung capacity (TLC) ≥ 80% predicted (Intermountain Thoracic Society \[ITS\])
• Single breath carbon monoxide diffusing capacity of the lung, hemoglobin-corrected (DLco-Hb) (uncorrected) ≥ 70% predicted
• For the subset of subjects having Doppler echocardiograms: right ventricular systolic pressure (RVSP) ≤ 40 mm Hg at Visit 1
• Written informed consent

You may not qualify if:

• Treatment with any type of antidiabetic drugs, other than sc insulin, within the preceding 12 weeks
• Two or more severe hypoglycemic episodes within 6 months of screening or episode of severe hypoglycemia between Visit 1 and Visit 5
• Any hospitalization or emergency room visit due to poor diabetic control within 6 months of Visit 1, or hospitalization or emergency room visit due to poor diabetic control between Visit 1 and Visit 5
• 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; history of foot ulcers; nontraumatic amputations due to gangrene; or vascular claudication
• Previous exposure to an inhaled insulin product within 3 months of Visit 1
• History of insulin pump use within 6 weeks of Visit 1
• Allergy or known hypersensitivity to insulin or to any of the drugs to be used in the trial, or a history of hypersensitivity to TI Inhalation Powder or to drugs with a similar chemical structure
• Significant improvement in pre- to postbronchodilator spirometry at Visit 1 (defined as an increase of 12% and 200 mL in either FEV1 or FVC)
• History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, or any other clinically important pulmonary disease (eg, obstructive sleep apnea) confirmed by pulmonary function testing or radiologic findings
• Inability to perform spirometry maneuvers meeting recommended American Thoracic Society (ATS) standards of acceptability and repeatability criteria
• Active respiratory infection (subject could return after 30 days from resolution for rescreening); if respiratory infection manifested after Visit 1 but before Visit 1 PFTs, subject was to be scheduled for PFTs after 30 days from resolution of respiratory infection. An additional hemoglobin was to be required
• Major organ system diseases, including:
• Seizure disorder
• Significant cardiovascular dysfunction or history within 3 months of Visit 1, eg, congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), or serious arrhythmia, myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks, or cerebrovascular accident
• Uncontrolled hypertension with a systolic blood pressure \> 180 mm Hg or diastolic blood pressure \> 110 mm Hg at Visit 1 despite pharmacologic treatment

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (22)

Diabetes/Lipid Management and Research Center

Huntington Beach, California, 92648, United States

Location

The Whittier Institute for Diabetes Clinical Trials

La Jolla, California, 92037, United States

Location

Dorothy L & James E Frank Diabetes Research Institute

San Mateo, California, 94401, United States

Location

Barbara Davis Center for Diabetes Young Adult Clinic

Aurora, Colorado, 80045, United States

Location

University of Miami Diabetes Research Institute

Miami, Florida, 33136, United States

Location

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30309, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112-2699, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Deaconess Billings Clinic Research Center

Billings, Montana, 59101, United States

Location

Mountain Diabetes & Endocrine Center

Asheville, North Carolina, 28803, United States

Location

Endocrine Research Physicians East PA

Greenville, North Carolina, 27834, United States

Location

Your Diabetes Endocrine Nutrition Group, Inc.

Mentor, Ohio, 44060, United States

Location

OHSU Diabetes Center Research Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

AM Diabetes and Endocrinology Center

Barrtlett, Tennessee, 38133, United States

Location

Dallas Diabetes & Endocrine Center

Dallas, Texas, 75230, United States

Location

Baylor Endocrine Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Diabetes Research Center -Fletcher Allen Health Care

South Burlington, Vermont, 05403, United States

Location

Diabetes Care Center

Seattle, Washington, 98105, United States

Location

Centro de Pesquisas em Diabetes Ltda

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

Location

CPClin-Centro de Pesquisas Clinicas

São Paulo, São Paulo, 01244-030, Brazil

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Glargine; Insulin Lispro

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

Limitations and Caveats

\- Early termination of trial leading to small numbers of subjects analyzed.

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: June 16, 2008
• First Posted: June 18, 2008
• Study Start: May 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: March 1, 2010
• Last Updated: October 16, 2014
• Results First Posted: October 16, 2014

Record last verified: 2014-10

Locations

BR (2); US (20)