The purpose of this 13 month study (12 month treatment period and 1 month follow-up period)
is to determine whether inhaled insulin is safe and effective in the treatment of type 2
diabetes.
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Inclusion Criteria:
- Men or women ≥ 18 and ≤ 80 years old
- Clinical diagnosis of type 2 diabetes mellitus
- HbA1c > 7. 0% and ≤ 11. 0%
- BMI ≤ 40 kg/m2
- Negative smoking status and urine cotinine test
- Written informed consent
- Receiving sc insulin 2-3 times daily administered as any of the following 3 regimens:
self-mix regimen, pre-mix regimen, or long-acting analogue and regular or
rapid-acting insulin analogue not to exceed 3 daily injections. Subjects may also
have received oral antidiabetic agents including metformin or thiazolidinediones.
- No dose adjustments for insulin and oral antidiabetic agents within the preceding 6
weeks.
- FEV1 ≥ 70% of NHANES III predicted; TLC) ≥ 80% of predicted (Intermountain Thoracic
Society); DLCO uncorrected ≥ 70% of predicted
Exclusion Criteria:
- Total daily dose of insulin ≥1. 4 IU/kg body weight
- Treatment with any sulfonylureas and/or meglitinides and/or alpha-glucosidase
inhibitors within the preceding 8 weeks
- Treatment with pramlintide acetate (Symlin®), and/or any incretins (e. g., exenatide
[Byetta®]) within the preceding 8 weeks
- Unstable diabetes mellitus control, defined as 2 or more episodes of severe
hypoglycemia (requiring third party intervention) and/or any hospitalization or
emergency room visit due to poor diabetic control or hyperglycemia requiring
hospitalization within the preceding 6 months
- Exposure to an inhaled insulin at any time, treatment with an investigational drug
within the preceding 3 months, and/or current participation in another clinical trial
- Allergy to insulin or to any drugs to be used as part of the clinical trial, or
history of hypersensitivity to the investigational drug or to drugs of similar
chemical structures
- 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) ≥ 3 x Upper Limit of Normal (ULN)(Includes active hepatitis A,
positive hepatitis B and/or hepatitis C serology)
- Serum creatinine > 1. 8 mg/dL in women and > 2. 0 mg/dL in men History of chronic
obstructive pulmonary disease (COPD), asthma (any history of bronchospasm or asthma
after the age of 14), and/or any other clinically important pulmonary disease
confirmed by documented history, pulmonary function testing, or radiologic findings
- Congestive heart disease graded as class III or class IV according to New York Heart
Association criteria and subjects currently being treated pharmacologically for
ventricular dysrhythmias using amiodarone
- History of myocardial infarction, cardiac surgery, coronary angioplasty, and/or
stroke within the preceding 3 months
- Symptomatic coronary artery disease, including crescendo angina, unstable angina,
and/or unstable or symptomatic cardiac arrhythmias
- Poorly controlled arterial hypertension despite pharmacologic treatment, defined as
systolic blood pressure (BP) > 180 mm Hg and/or diastolic BP > 110 mm Hg at screening
- History of malignancy within the preceding 5 years (other than excised basal cell
carcinoma of the skin), any history of lung neoplasm, and/or subjects with current or
previous chemotherapy or radiation therapy that may result in pulmonary toxicity
- History of acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), or
positive human immunodeficiency virus (HIV) serology
- Prior diagnosis of systemic autoimmune or collagen vascular disease requiring
previous or current treatment with systemic corticosteroids, cytotoxic drugs, or
penicillamine
- Visit 1/Screening (Week -3), but prior to Visit 1 PFTs and before Visit 3/Baseline
(Week 0), subject will be scheduled for PFTs after 30 days from resolution of
respiratory infection. An additional hemoglobin and urine β-HCG (for women of
childbearing potential age only) will be required
- Women who are pregnant, lactating or planning to become pregnant
- Women of childbearing potential (defined as pre-menopausal and not surgically
sterilized or postmenopausal 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 with a spermicide, or intrauterine
devices
- Current drug and/or alcohol abuse
- Subjects who in the opinion of the Investigator will be unable to comply with the
requirements of the protocol
- Severe complications of diabetes mellitus, in the opinion of the Investigator,
including: symptomatic autonomic neuropathy, disabling peripheral neuropathy, active
proliferative retinopathy; nephropathy with renal failure, renal transplant and/or
dialysis; history of foot ulcers; nontraumatic amputations due to gangrene;and/or
vascular claudication
- Any other concurrent medical or major psychiatric condition which, in the opinion of
the Investigator, makes the subject unsuitable for the clinical trial, or could limit
the validity of the ICF and/or impair the subject's ability to participate in the
trial
- Inability to perform PFT maneuvers meeting recommended American Thoracic Society
(ATS) acceptability and repeatability criteria.
Centro Endocrinologic Tiempo, Buenos Aires C1117ABH, Argentina
Centro Medico Dra De Salvo, Buenos Aires C1426ABP, Argentina
Cons Asoc de Endocrinologia, Buenos Aires C1425AGC, Argentina
FUNDAPRES/CIMel, Buenos Aires B1824KAJ, Argentina
Hospital Italiano de Buenos Aires, Buenos Aires C1181ACH, Argentina
Universidade Estabual de Maringa, Maringa Parana 87020-900, Brazil
Nucleo de Medicina Integrada, Mogi das Cruzes 08780-090, Brazil
Ccbr Brasil Centro de Analises e Pesquisas Clinicas Ltda, Rio de Janeiro 22271-100, Brazil
Instituto Estadual De Diabetes e Endocrinologia Luis Capriglione, Rio de Janeiro 20211-340, Brazil
Hospital Guilherme Alvaro, Santos 11045-904, Brazil
Blumenau Servicos Medicos S/C Ltda, Sao Paulo 05302-001, Brazil
Centro de Pesquisa Clinica e Medicina Avancada, Sao Paulo 05437-010, Brazil
CPClin-Centro de Pesquisas Clinicas, Sao Paulo 01244-030, Brazil
Hospital do Rim e Hipertensao, Sao Paulo 04025-011, Brazil
Instituto da Saude e Bem Estar da Mulher, Sao Paulo 04062-003, Brazil
Hospital Clinico Pontificia Universidad Catolica de Chile, Santiago, Chile
Hospital San Borja ArriaranUniversidad de Chile, Santiago, Chile
Hospital Santa Engracia-CIMA, Garza Garcia 66260, Mexico
Centro de Estudios en Diabetes, Mexico City 01120, Mexico
Cifbiotec, Mexico City CP14050, Mexico
NZOZ Diabetologiczna Poradnia Specjalistyczna, Warszawa 01-911, Poland
City Clinical Hospital # 61, Moscow 119 048, Russian Federation
NI Central Clinical Hospital of RAS, Moscow 117 593, Russian Federation
Centro Médico Teknon, Barcelona 08022, Spain
Hospital del Mar (Cano), Barcelona 08003, Spain
Hospital Ramon y Cajal, Madrid 28034, Spain
Hospital Universitario de la Princessa, Madrid 28006, Spain
Corporacion Sanitaria Parc Tauli Unidad de Endocrinologia, Sabadell 08208, Spain
Complejo Hospitalario Virgen del Rocio, Sevilla 41013, Spain
Hospital Virgen Macarena (policlinico) 2ª planta Servicio de Endocrinologia y Nutricion, Sevilla 41071, Spain
Guy's & St Thomas Hospital, London SE1 9RT, United Kingdom
Yaxley Group Practice, Peterborough PE7 3JL, United Kingdom
Coastal Clinical Research Inc, Mobile, Alabama 36608, United States
Complejo Hospitalario Nuestra Senora de Valme, Sevilla, Andalucia 41014, Spain
Quality of Life Medical & Research Center, Tucson, Arizona 85712, United States
Southern Arizona VA Healthcare System, Tucson, Arizona 85723, United States
Tucson Clinical Research, Tucson, Arizona 85741, United States
Hospital de Mataro, Mataro, Barcelona 08304, Spain
Hospital Interzonal de Agudos Pedro Fiorito, Avellaneda, Buenos Aires B1870ARG, Argentina
International Clinical Research Network, Chula Vista, California 91911, United States
Saad Hijazi MD Inc, Fresno, California 93710, United States
Valley Research, Fresno, California 93720, United States
Diabetes/Lipid Management and Research Center, Huntington Beach, California 92648, United States
South Bay Clinical Research, Inglewood, California 90301, United States
Southern California Endocrine Center, Pasadena, California 91105, United States
Coastal Biomedical Research Inc, Santa Monica, California 90404, United States
Diabetes Research Center, Tustin, California 92780, United States
Instituto Mexicano de Investigacion, Mexico City, Durango 06700, Mexico
International Research Associates LLC, Miami, Florida 33156, United States
University of Miami Diabetes Research Institute, Miami, Florida 33136, United States
Laureate Clinical Research Group, Atlanta, Georgia 30308, United States
Atlanta Pharmaceutical Research Center, Dunwoody, Georgia 30338, United States
North Atlanta Endocrinology & Diabetes PC, Lawrenceville, Georgia 30045, United States
Atlanta Center for Clinical Research, Roswell, Georgia 30075, United States
Birchwood Surgery, Letchworth, Herts SG6 4UB, United Kingdom
Lister Hospital, Stevenage, Herts SG1 4AB, United Kingdom
John H Stoger Jr Hospital of Cook County, Chicago, Illinois 60612, United States
Clintell Inc, Skokie, Illinois 60076, United States
Clintell Inc (Ellyin), Skokie, Illinois 60077, United States
Medical Research of Louisiana, Metairie, Louisiana 70002, United States
Hospital OCA, Monterrey, Nuevo Leon, MX 64000, Mexico
Joslin Diabetes Center University of Maryland Medicine, Baltimore, Maryland 21201, United States
James A Dicke MDPA, Towson, Maryland 21204, United States
Wayne State University, Detroit, Michigan 48201, United States
Michigan Institute of Medicine, Livonia, Michigan 48152, United States
KMED Research, St Clair Shores, Michigan 48081, United States
Radiant Research Inc (Minneapolis), Edina, Minnesota 55435, United States
Center for Urologic Clinical Trials University of Minnesota, Minneapolis, Minnesota 55455, United States
International Diabetes Center, Minneapolis, Minnesota 55416, United States
MedEx Healthcare Research Inc, St Louis, Missouri 63117, United States
Amin Radparvar's Private Practice, St Peters, Missouri 63376, United States
Billings Clinic Research Division, Billings, Montana 59101, United States
Montana Health Research Institute, Billings, Montana 59102, United States
Creighton Diabetes Center, Omaha, Nebraska 68131, United States
New Mexico Clinical Research & Osteoporosis Center, Albuquerque, New Mexico 87106, United States
University of New Mexico HCS, Albuquerque, New Mexico 87131, United States
Winthrop University Hospital, Mineola, New York 11501, United States
North Shore Diabetes and Endocrine Associates, New Hyde Park, New York 11042, United States
Univeristy of Physicians Group Endocrine Division, Staten Island, New York 10301, United States
Sensenbrenner Primary Care, Charlotte, North Carolina 28277, United States
East Carolina University (Tanenberg), Greenville, North Carolina 27834, United States
Physician's East PA, Greenville, North Carolina 27834, United States
Hospital Universitario Dr Jose E Gonzalez, Monterrey, Nuevo Leon 64460, Mexico
Valley Medical Primary Care, Centerville, Ohio 45459, United States
Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States
Providence Health Partners - Center of Clinical Research, Dayton, Ohio 45439, United States
Cleveland Clinic Health System, East Cleveland, Ohio 44112, United States
Wells Institute for Health Awareness, Kettering, Ohio 45429, United States
Keele Medical Place, Downsview, Ontario M3M 3E5, Canada
Quest Clinical Trials, Markham, Ontario L6B 1A1, Canada
Lifestyle Metabolism Center, Oakville, Ontario L6H 3P1, Canada
Sarnia Institute of Clinical Research, Sarnia, Ontario N7T 4X3, Canada
Lifestyle Metabolism Center, Thornhill, Ontario L4J 8L7, Canada
Lifestyle Metabolism Center, Toronto, Ontario M4R 2G4, Canada
Lane Medical Research Group, Eugene, Oregon 97404, United States
Oregon Medical Group Clinical Resesarch, Eugene, Oregon 97401, United States
Covance CRU Inc., Portland, Oregon 97239, United States
New Hope Research of Oregon, Portland, Oregon 97219, United States
Portland Diabetes & Endocrinology Center, Portland, Oregon 97210, United States
Oddzial Chorob Wewnetrznych, Bialystock, POL 15-950, Poland
NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny, Bialystok, POL 15-435, Poland
Katedra I Klinika Chorob Metabolicznych Collegium Medicum Uniwersytety Jagiellonskiego, Krakow, POL 31 501, Poland
Instytut Centrum Zdrowia (009) Matki Polki, Lodz, POL 93-338, Poland
Klliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi, Lodz, POL 90 153, Poland
Szpital Kolejowy im Dr w Roeflera(009) Oddzial Gastorenterologii, Pruszkow, POL 05 800, Poland
Pennsylvania Research Institute, Bensalem, Pennsylvania 19020, United States
Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States
NHI Kemerovo Regional Clinical Hospital, Kemerovo, RUS 650061, Russian Federation
Moscow City Clinical Hospital # 13, Moscow, RUS 115280, Russian Federation
NEI HPE Moscow State University of Medicine and Dentistry of FAHSD City Clinical Hospital #70, Moscow, RUS 111399, Russian Federation
NI Principal Military Clinical Hospital n a academician N.N. Burdenko of the Ministry of Defense, Moscow, RUS 105229, Russian Federation
RAAMS Endocrinology and Diabetology Department, Moscow, RUS 125315, Russian Federation
SEI HPE Moscow Medical Academy IM Sechenov of Roszdrav Clinic of Endocrinology, Moscow, RUS 119435, Russian Federation
SI Internal Affairs of Moscow- Clinical Hospital, Moscow, RUS 125299, Russian Federation
NEI HPE Smolensk State Medical Academy of FAHSD RNHI Smolensk Regional Clinical Hospital, Smolensk, RUS 214018, Russian Federation
Central Medical Sanitary Unit #122, St Petersburg, RUS 194291, Russian Federation
Pavlov State Medical Univ of St Petersburg, St Petersburg, RUS 197022, Russian Federation
St Petersburg NHI City Polytclinic #77 City Diabetological Center #4, St Petersburg, RUS 193012, Russian Federation
MCHI Medical Sanitary Unit of Novo-Yaroslavsky Oil Refining Plant, Yaroslavl, RUS 150023, Russian Federation
MHI Clinical Hospital for Emergency Care na NV Soloviev, Yaroslavl, RUS 150003, Russian Federation
NHI Yaroslavl Regional Clinical Hospital, Yaroslavl, RUS 150062, Russian Federation
Hospital del Salvador, Santiago, Region Metropolitana, Chile
Hospital Padre Alberto Hurtado, Santiago, Region Metropolitana, Chile
Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul 90035-903, Brazil
Hospital Sao Lucas da PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
Upstate Pharmaceutical Research, Greenville, South Carolina 29615, United States
Southeastern Research Associates Inc, Taylors, South Carolina 29687, United States
AM Diabetes and Endocrinology Center, Bartlett, Tennessee 38133, United States
Memphis Internal Medicine PLLC, Memphis, Tennessee 38119, United States
The Endocrine Clinic, Memphis, Tennessee 38119, United States
Israel Hartman MD, Arlington, Texas 76014, United States
South Arlington Primary Care Assoc PA, Arlington, Texas 76017, United States
Baylor Endocrine Center, Dallas, Texas 75246, United States
Dallas Diabetes & Endocrine Center, Dallas, Texas 75230, United States
Galenos Research, Dallas, Texas 75251, United States
North Texas Endocrine Center, Dallas, Texas 75231, United States
Radiant Research Dallas-North, Dallas, Texas 75231, United States
Spuhler Medical Associates, Friendswood, Texas 77546, United States
Clinical Trial Network, Houston, Texas 77074, United States
Covenant Clinic Research, San Antonio, Texas 78229, United States
Diabetes & Glandular Disease Research Assoc PA, San Antonio, Texas 78229, United States
Quality Assurance Research Center Inc, San Antonio, Texas 78205, United States
SAM Clinical Research Center, San Antonio, Texas 78229, United States
CITDEEM - Centro de Investigacion y Tratamiento En Diabetes y Enfermedades Endocrino-Metabolicas, San Miguel de Tucuman, Tucuman 4000, Argentina
Salt Lake Research, Salt Lake City, Utah 84107, United States
Clinical Research Associates of Tidewater, Norfolk, Virginia 23507, United States
Sentara Medical Group, Norfolk, Virginia 23502, United States
Larry D Stonesifer MD Inc PS, Federal Way, Washington 98003, United States
Rainier Clinical Research Center Inc, Renton, Washington 98055, United States
Cedar Research, Tacoma, Washington 98405, United States
Liberty Research Center, Tacoma, Washington 98405, United States