Safety and Efficacy of Technosphere® Insulin Inhalation Powder and Lantus® Compared to Humalog® and Lantus® Over 16-Weeks
Overview[ - collapse ][ - ]
| Purpose | 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. |
|---|---|
| Condition | Diabetes Type 1 |
| Intervention | Drug: Technosphere Insulin Drug: Lantus Drug: Humalog |
| Phase | Phase 3 |
| Sponsor | Mannkind Corporation |
| Responsible Party | Mannkind Corporation |
| ClinicalTrials.gov Identifier | NCT00700622 |
| First Received | June 16, 2008 |
| Last Updated | August 3, 2010 |
| Last verified | August 2010 |
Tracking Information[ + expand ][ + ]
| First Received Date | June 16, 2008 |
|---|---|
| Last Updated Date | August 3, 2010 |
| Start Date | May 2008 |
| Estimated Primary Completion Date | March 2010 |
| Current Primary Outcome Measures | efficacy endpoint is the change from Visit 5 to Visit 14 in A1c [Time Frame: 16 weeks] [Designated as safety issue: No] |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Safety and Efficacy of Technosphere® Insulin Inhalation Powder and Lantus® Compared to Humalog® and Lantus® Over 16-Weeks |
|---|---|
| Official Title | A Phase3, Multi-Center, Open-Label, Randomized, Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Insulin Inhalation Powder in Combination With Lantus® Versus Humalog® in Combination With Lantus® in Subjects With Type 1 Diabetes Mellitus Over a 16-Week Treatment Period |
| 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. |
| Detailed Description | Not Provided |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Diabetes Type 1 |
| Intervention | Drug: Technosphere Insulin Technosphere Insulin Inhalation Powder 15U or 30U Drug: Lantus Lantus-injectible supplied as 3mL (300 units) pens Drug: Humalog Humalog autopen cartridges pre-filled with 3mL (300 units) |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 137 |
| Estimated Completion Date | March 2010 |
| Estimated Primary Completion Date | November 2009 |
| Eligibility Criteria | Inclusion Criteria: 1. Males and females = 18 and = 80 years of age; 4. Stable anti-diabetic regimen of sc insulin therapy at a total daily dose (TDD) = 1.5 IU/kg/day; 5. A1c > 7.0% and = 9.0%; 6. C-peptide level of = 0.30 pmol/mL; 7. Non-smokers (includes cigarettes, cigars, pipes, and chewing tobacco) for the preceding = 6 months; 8. Negative Urine Cotinine Test, defined as = 100 ng/mL 9. PFTs--• FEV1 = 70% NHANES III Predicted 9. PFTs--•• FEV1 as a percentage of FEV1/FVC = 70% Third National Health and Nutrition Examination Survey (NHANES III) Predicted; 9. PFTs--•• Total lung capacity (TLC) = 80% Predicted (Intermountain Thoracic Society [ITS]); 9. PFTs--•• DLco (unc) = 70% of Predicted (Miller); 10.For the subset of subjects having Doppler echocardiograms: right ventricular systolic pressure (RVSP) = 40 mm Hg at Visit 1 Doppler echocardiogram 11. Written Informed Consent. 2 Clinical diagnosis of type 1 diabetes mellitus greater than 12 months; 3. Body mass index (BMI) of = 30 kg/m2; Exclusion Criteria: - Earlier diagnosis of systemic autoimmune, or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine, 13. Current or previous chemotherapy or radiation therapy that may result in pulmonary toxicity; 14. Use of medications prescribed for weight loss (eg, sibutramine, orlastat) within 12 weeks of Visit 1. 15. Any history of or current use of Amiodarone; 16. Clinically significant abnormalities on screening laboratory evaluation (unless discussed with and approved by the Medical Monitor); 17. Female subjects who are pregnant, lactating, or planning to become pregnant during the clinical trial period; 19. Current drug or alcohol abuse, or a history of drug or alcohol abuse, that, in the opinion of the PI, would not make the subject a suitable candidate for participation in the clinical trial; 20. Exposure to any investigational medications or devices within the previous 30 days prior to trial entry, or participation in another clinical trial while participating in this trial; 21. Unable and/or unlikely to comprehend and/or follow the trial protocol (including SBGM, diabetes education); 22. Unable and/or unlikely to comprehend how to use the MedTone? Inhaler or inability to use the device; 23. Unable and/or unlikely to follow a meal plan that includes at least 2 meals/day (with or without a third meal and/or additional snacks); 18. Female subjects of childbearing potential (defined as pre-menopausal and not surgically sterilized or post-menopausal for less than 2 years) not practicing adequate birth control. Adequate birth control is defined as using oral, percutaneous, and/or transdermal contraceptives; condoms and diaphragms (double barrier) with a spermicide; or intrauterine devices. Post-menopausal for the purposes of this clinical trial include: amenorrhea for 2 or more years or surgically sterile 5. Previous exposure to an inhaled insulin product within 3 months of Visit 1; 6. History of insulin pump use within 6 weeks of Visit 1 7. 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; 8. Significant improvement in pre- to post-bronchodilator spirometry (defined as an increase of 12% AND 200 mL in either FEV1 or FVC) at Visit 1; 9. History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, and/or any other clinically important pulmonary disease (eg, obstructive sleep apnea), confirmed by pulmonary function testing, and/or radiologic findings; 10. Inability to perform PFT maneuvers meeting recommended American Thoracic Society (ATS) standards of acceptability and repeatability criteria; 11. Active respiratory infection (subject may return after 30 days from resolution for re-screening); if respiratory infection manifests after Visit 1 but prior to Visit 1 PFTs, subject will be scheduled for PFTs after 30 days from resolution of respiratory infection. An additional hemoglobin will be required; 12 Major organ system diseases including: Seizure disorder, - Significant cardiovascular dysfunction and/or history within 3 months of Visit 1, eg, congestive heart failure (New York Heart Association [NYHA] Class III or IV) (Appendix C), or serious arrhythmia, myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks, or cerebrovascular accident, - Uncontrolled hypertension with a systolic blood pressure of > 180 mm Hg, and/or diastolic blood pressure > 110 mm Hg at Visit 1, despite pharmacologic treatment, - Nephrotic syndrome, or renal dysfunction or disease, serum creatinine > 2.0 mg/dL (0.11 mmol/L) in males and > 1.8 mg/dL ( 0.1 mmol/L) in females, and/or blood urea nitrogen (BUN) > 50 mg/dL (2.8 mmol/L), - Cancer (other than excised cutaneous basal cell carcinoma) within the past 5 years or any history of lung neoplasms, 1. Treatment with any type of anti-diabetic drugs, other than sc insulin, within the preceding 12 weeks; 2. Two or more severe hypoglycemic episodes within 6 months of screening or episode of severe hypoglycemia between Visit 1 and Visit 5; 3. 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; 4. Severe complications of diabetes, in the opinion of the PI, including symptomatic autonomic neuropathy; disabling peripheral neuropathy; active proliferative retinopathy (Appendix A); nephropathy with renal failure, renal transplant, and/or dialysis; history of foot ulcers; non-traumatic amputations due to gangrene; and/or vascular claudication; - History of active viral, and/or cirrhotic hepatic disease, and/or abnormal liver enzymes, as evidenced by serum aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT) ? 3x upper limit of normal (ULN), - Active infection (ie, human immunodeficiency virus [HIV], hepatitis), or history of severe infection within 30 days of Visit 1, - Anemia (hemoglobin value = 10.5 g/dL for females or = 11.5 g/dL for males), - Earlier diagnosis of systemic autoimmune, or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine, 24. A lack of compliance with medication or procedures that, in the PI's opinion, may affect the clinical trial data or the subject's safety, and which precludes the subject from further participation in the clinical trial; 25. Any other concurrent medical or major psychiatric condition which, in the opinion of the PI makes the subject unsuitable for the clinical trial, or could limit the validity of the informed consent, and/or impair the subject's ability to participate in the trial. 26. For the subset of subjects having Doppler echocardiograms: - Subjects with left ventricular ejection fraction (LVEF) = 35% at Visit 1 echocardiogram; - Subjects with known history of sickle cell disease; - Previous use of Redux® (dexfenfluramine) or Pondimin® (fenfluramine); - History of valvular heart disease, including mild or greater aortic insufficiency, or moderate or greater mitral insufficiency; - Significant cardiovascular dysfunction and/or history within 12 months of Visit 1, eg, congestive heart failure (NYHA Class III or IV) (Appendix C), or serious arrhythmia, treatment with medications to control/treat arrhythmias, myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks, or cerebrovascular accident; - History of pulmonary embolism or deep venous thrombosis in the 12 months prior to Screening. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Brazil |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00700622 |
|---|---|
| Other Study ID Numbers | MKC-TI-117 |
| Has Data Monitoring Committee | No |
| Information Provided By | Mannkind Corporation |
| Study Sponsor | Mannkind Corporation |
| Collaborators | Not Provided |
| Investigators | Not Provided |
| Verification Date | August 2010 |
Locations[ + expand ][ + ]
| Diabetes/Lipid Management and Research Center | Huntington Beach, California, United States, 92648 |
|---|---|
| The Whittier Institute for Diabetes Clinical Trials | La Jolla, California, United States, 92037 |
| Dorothy L & James E Frank Diabetes Research Institute | San Mateo, California, United States, 94401 |
| Barbara Davis Center for Diabetes Young Adult Clinic | Aurora, Colorado, United States, 80045 |
| University of Miami School of Medicine | Miami, Florida, United States, 33136 |
| University of Miami Diabetes Research Institute | Miami, Florida, United States, 33136 |
| Atlanta Diabetes Associates | Atlanta, Georgia, United States, 30309 |
| Tulane University Health Sciences Center | New Orleans, Louisiana, United States, 70112-2699 |
| Washington University School of Medicine | St. Louis, Missouri, United States, 63110 |
| Deaconess Billings Clinic Research Center | Billings, Montana, United States, 59101 |
| Mountain Diabetes & Endocrine Center | Asheville, North Carolina, United States, 28803 |
| Endocrine Research Physicians East PA | Greenville, North Carolina, United States, 27834 |
| Your Diabetes Endocrine Nutrition Group, Inc. | Mentor, Ohio, United States, 44060 |
| OHSU Diabetes Center Research Oregon Health & Science University | Portland, Oregon, United States, 97239 |
| AM Diabetes and Endocrinology Center | Barrtlett, Tennessee, United States, 38133 |
| University of Texas Southwestern Medical Center | Dallas, Texas, United States, 75390 |
| Baylor Endocrine Center | Dallas, Texas, United States, 75246 |
| Dallas Diabetes & Endocrine Center | Dallas, Texas, United States, 75230 |
| Diabetes Research Center -Fletcher Allen Health Care | South Burlington, Vermont, United States, 05403 |
| Diabetes Care Center | Seattle, Washington, United States, 98105 |
| Centro de Pesquisas em Diabetes Ltda | Porto Alegre, RS, Brazil, -90035-170 |
| CPClin-Centro de Pesquisas Clinicas | Sao Paulo, Brazil, 01244-030 |