Efficacy and Safety in Subjects With Type 2 Diabetes Receiving Subcutaneous Basal Insulin and Prandial Inhalation of Technosphere/Insulin Versus Subcutaneous Premixed Insulin Therapy Over a 52-Week Treatment Period and a 4-Week Follow-up

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00309244
Recruitment Status : Completed
First Posted : March 31, 2006
Results First Posted : October 16, 2014
Last Update Posted : October 16, 2014
Information provided by (Responsible Party):
Mannkind Corporation

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diabetes Type 2 Drug: Technosphere® Insulin Inhalation Powder Drug: 70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin) Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 677 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Prospective, Multi-Center, Open-Label, Randomized, Controlled Clinical Trial Comparing the Efficacy and Safety in Subjects With Type 2 Diabetes Receiving Subcutaneous Basal Insulin and Prandial Inhalation of Technosphere /Insulin Versus Subcutaneous Premixed Insulin Therapy Over a 52-Week Treatment Period and a 4-Week Follow-up
Study Start Date : February 2006
Actual Primary Completion Date : August 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: TI + Insulin glargine
Technosphere® Insulin Inhalation Powder + insulin glargine
Drug: Technosphere® Insulin Inhalation Powder
Inhalation, 15U/30U

Active Comparator: BPR 70/30
70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin)
Drug: 70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin)
BPR 70/30, which is a premix of intermediate acting and rapid acting insulin given sc

Primary Outcome Measures :
  1. Change From Baseline in HbA1c to Week 52 [ Time Frame: Baseline to Week 52 ]

Secondary Outcome Measures :
  1. Change From Baseline in Weight to Week 52 [ Time Frame: Baseline to Week 52 ]
  2. Change From Baseline in Fasting Plasma Glucose to Week 52 [ Time Frame: Baseline to Week 52 ]
  3. Number of Subjects Achieving Week 52 HbA1c Levels Less Than or Equal to 7.0% [ Time Frame: Week 52 ]
  4. Incidence of Total Hypoglycemia [ Time Frame: 52 Weeks ]
    Defined as hypoglycemic symptoms that are relieved with carbohydrate intake or blood glucose measurement <= 63 mg/dL, regardless of symptoms.

  5. Incidence of Severe Hypoglycemia [ Time Frame: 52 Weeks ]

    Severe hypoglycemia occurs when all 3 of the following occur simultaneously:

    • Subject requires the assistance of another person;
    • Subject exhibits at least 1 cognitive neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, seizure, loss of consciousness);
    • Measured BG is ≤ 49 mg/dL (2.7 mmol/L), or, in the absence of a BG measurement, clinical symptoms are reversed by oral carbohydrates, sc glucagon or intravenous glucose administration; OR,
    • Measured BG is ≤ 36 mg/dL (2.0 mmol/L) with or without symptoms.

  6. Total Hypoglycemia Event Rate [ Time Frame: 52 Weeks ]
    Number of Hypoglycemic Events/Total Subject Exposure Time (in months)

  7. Severe Hypoglycemia Event Rate [ Time Frame: 52 Weeks ]
    Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00309244

  Hide Study Locations
United States, Alabama
Coastal Clinical Research Inc
Mobile, Alabama, United States, 36608
United States, Arizona
Quality of Life Medical & Research Center
Tucson, Arizona, United States, 85712
Southern Arizona VA Healthcare System
Tucson, Arizona, United States, 85723
Tucson Clinical Research
Tucson, Arizona, United States, 85741
United States, California
International Clinical Research Network
Chula Vista, California, United States, 91911
Saad Hijazi MD Inc
Fresno, California, United States, 93710
Valley Research
Fresno, California, United States, 93720
Diabetes/Lipid Management and Research Center
Huntington Beach, California, United States, 92648
South Bay Clinical Research
Inglewood, California, United States, 90301
Southern California Endocrine Center
Pasadena, California, United States, 91105
Coastal Biomedical Research Inc
Santa Monica, California, United States, 90404
Diabetes Research Center
Tustin, California, United States, 92780
United States, Florida
University of Miami Diabetes Research Institute
Miami, Florida, United States, 33136
International Research Associates LLC
Miami, Florida, United States, 33156
United States, Georgia
Laureate Clinical Research Group
Atlanta, Georgia, United States, 30308
Atlanta Pharmaceutical Research Center
Dunwoody, Georgia, United States, 30338
North Atlanta Endocrinology & Diabetes PC
Lawrenceville, Georgia, United States, 30045
Atlanta Center for Clinical Research
Roswell, Georgia, United States, 30075
United States, Illinois
John H Stoger Jr Hospital of Cook County
Chicago, Illinois, United States, 60612
Clintell Inc
Skokie, Illinois, United States, 60076
Clintell Inc (Ellyin)
Skokie, Illinois, United States, 60077
United States, Louisiana
Medical Research of Louisiana
Metairie, Louisiana, United States, 70002
United States, Maryland
Joslin Diabetes Center University of Maryland Medicine
Baltimore, Maryland, United States, 21201
James A Dicke MDPA
Towson, Maryland, United States, 21204
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
Michigan Institute of Medicine
Livonia, Michigan, United States, 48152
KMED Research
St Clair Shores, Michigan, United States, 48081
United States, Minnesota
Radiant Research Inc (Minneapolis)
Edina, Minnesota, United States, 55435
International Diabetes Center
Minneapolis, Minnesota, United States, 55416
Center for Urologic Clinical Trials University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
MedEx Healthcare Research Inc
St Louis, Missouri, United States, 63117
Amin Radparvar's Private Practice
St Peters, Missouri, United States, 63376
United States, Montana
Billings Clinic Research Division
Billings, Montana, United States, 59101
Montana Health Research Institute
Billings, Montana, United States, 59102
United States, Nebraska
Creighton Diabetes Center
Omaha, Nebraska, United States, 68131
United States, New Mexico
New Mexico Clinical Research & Osteoporosis Center
Albuquerque, New Mexico, United States, 87106
University of New Mexico HCS
Albuquerque, New Mexico, United States, 87131
United States, New York
Winthrop University Hospital
Mineola, New York, United States, 11501
North Shore Diabetes and Endocrine Associates
New Hyde Park, New York, United States, 11042
Univeristy of Physicians Group Endocrine Division
Staten Island, New York, United States, 10301
United States, North Carolina
Sensenbrenner Primary Care
Charlotte, North Carolina, United States, 28277
East Carolina University (Tanenberg)
Greenville, North Carolina, United States, 27834
Physician's East PA
Greenville, North Carolina, United States, 27834
United States, Ohio
Valley Medical Primary Care
Centerville, Ohio, United States, 45459
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Providence Health Partners - Center of Clinical Research
Dayton, Ohio, United States, 45439
Cleveland Clinic Health System
East Cleveland, Ohio, United States, 44112
Wells Institute for Health Awareness
Kettering, Ohio, United States, 45429
United States, Oregon
Oregon Medical Group Clinical Resesarch
Eugene, Oregon, United States, 97401
Lane Medical Research Group
Eugene, Oregon, United States, 97404
Portland Diabetes & Endocrinology Center
Portland, Oregon, United States, 97210
New Hope Research of Oregon
Portland, Oregon, United States, 97219
Covance CRU Inc.
Portland, Oregon, United States, 97239
United States, Pennsylvania
Pennsylvania Research Institute
Bensalem, Pennsylvania, United States, 19020
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Upstate Pharmaceutical Research
Greenville, South Carolina, United States, 29615
Southeastern Research Associates Inc
Taylors, South Carolina, United States, 29687
United States, Tennessee
AM Diabetes and Endocrinology Center
Bartlett, Tennessee, United States, 38133
Memphis Internal Medicine PLLC
Memphis, Tennessee, United States, 38119
The Endocrine Clinic
Memphis, Tennessee, United States, 38119
United States, Texas
Israel Hartman MD
Arlington, Texas, United States, 76014
South Arlington Primary Care Assoc PA
Arlington, Texas, United States, 76017
Dallas Diabetes & Endocrine Center
Dallas, Texas, United States, 75230
North Texas Endocrine Center
Dallas, Texas, United States, 75231
Radiant Research Dallas-North
Dallas, Texas, United States, 75231
Baylor Endocrine Center
Dallas, Texas, United States, 75246
Galenos Research
Dallas, Texas, United States, 75251
Spuhler Medical Associates
Friendswood, Texas, United States, 77546
Clinical Trial Network
Houston, Texas, United States, 77074
Quality Assurance Research Center Inc
San Antonio, Texas, United States, 78205
Covenant Clinic Research
San Antonio, Texas, United States, 78229
Diabetes & Glandular Disease Research Assoc PA
San Antonio, Texas, United States, 78229
SAM Clinical Research Center
San Antonio, Texas, United States, 78229
United States, Utah
Salt Lake Research
Salt Lake City, Utah, United States, 84107
United States, Virginia
Sentara Medical Group
Norfolk, Virginia, United States, 23502
Clinical Research Associates of Tidewater
Norfolk, Virginia, United States, 23507
United States, Washington
Larry D Stonesifer MD Inc PS
Federal Way, Washington, United States, 98003
Rainier Clinical Research Center Inc
Renton, Washington, United States, 98055
Cedar Research
Tacoma, Washington, United States, 98405
Liberty Research Center
Tacoma, Washington, United States, 98405
Hospital Interzonal de Agudos Pedro Fiorito
Avellaneda, Buenos Aires, Argentina, B1870ARG
CITDEEM - Centro de Investigacion y Tratamiento En Diabetes y Enfermedades Endocrino-Metabolicas
San Miguel de Tucuman, Tucuman, Argentina, 4000
Buenos Aires, Argentina, B1824KAJ
Centro Endocrinologic Tiempo
Buenos Aires, Argentina, C1117ABH
Hospital Italiano de Buenos Aires
Buenos Aires, Argentina, C1181ACH
Cons Asoc de Endocrinologia
Buenos Aires, Argentina, C1425AGC
Centro Medico Dra De Salvo
Buenos Aires, Argentina, C1426ABP
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
Hospital Sao Lucas da PUCRS
Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
Universidade Estabual de Maringa
Maringa Parana, Brazil, 87020-900
Nucleo de Medicina Integrada
Mogi das Cruzes, Brazil, 08780-090
Instituto Estadual De Diabetes e Endocrinologia Luis Capriglione
Rio de Janeiro, Brazil, 20211-340
Ccbr Brasil Centro de Analises e Pesquisas Clinicas Ltda
Rio de Janeiro, Brazil, 22271-100
Hospital Guilherme Alvaro
Santos, Brazil, 11045-904
CPClin-Centro de Pesquisas Clinicas
Sao Paulo, Brazil, 01244-030
Hospital do Rim e Hipertensao
Sao Paulo, Brazil, 04025-011
Instituto da Saude e Bem Estar da Mulher
Sao Paulo, Brazil, 04062-003
Blumenau Servicos Medicos S/C Ltda
Sao Paulo, Brazil, 05302-001
Centro de Pesquisa Clinica e Medicina Avancada
Sao Paulo, Brazil, 05437-010
Canada, Ontario
Keele Medical Place
Downsview, Ontario, Canada, M3M 3E5
Quest Clinical Trials
Markham, Ontario, Canada, L6B 1A1
Lifestyle Metabolism Center
Oakville, Ontario, Canada, L6H 3P1
Sarnia Institute of Clinical Research
Sarnia, Ontario, Canada, N7T 4X3
Lifestyle Metabolism Center
Thornhill, Ontario, Canada, L4J 8L7
Lifestyle Metabolism Center
Toronto, Ontario, Canada, M4R 2G4
Hospital del Salvador
Santiago, Region Metropolitana, Chile
Hospital Padre Alberto Hurtado
Santiago, Region Metropolitana, Chile
Hospital Clinico Pontificia Universidad Catolica de Chile
Santiago, Chile
Hospital San Borja ArriaranUniversidad de Chile
Santiago, Chile
Instituto Mexicano de Investigacion
Mexico City, Durango, Mexico, 06700
Hospital OCA
Monterrey, Nuevo Leon, MX, Mexico, 64000
Hospital Universitario Dr Jose E Gonzalez
Monterrey, Nuevo Leon, Mexico, 64460
Hospital Santa Engracia-CIMA
Garza Garcia, Mexico, 66260
Centro de Estudios en Diabetes
Mexico City, Mexico, 01120
Mexico City, Mexico, CP14050
Oddzial Chorob Wewnetrznych
Bialystock, POL, Poland, 15-950
NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny
Bialystok, POL, Poland, 15-435
Katedra I Klinika Chorob Metabolicznych Collegium Medicum Uniwersytety Jagiellonskiego
Krakow, POL, Poland, 31 501
Klliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
Lodz, POL, Poland, 90 153
Instytut Centrum Zdrowia (009) Matki Polki
Lodz, POL, Poland, 93-338
Szpital Kolejowy im Dr w Roeflera(009) Oddzial Gastorenterologii
Pruszkow, POL, Poland, 05 800
NZOZ Diabetologiczna Poradnia Specjalistyczna
Warszawa, Poland, 01-911
Russian Federation
NHI Kemerovo Regional Clinical Hospital
Kemerovo, RUS, Russian Federation, 650061
NI Principal Military Clinical Hospital n a academician N.N. Burdenko of the Ministry of Defense
Moscow, RUS, Russian Federation, 105229
NEI HPE Moscow State University of Medicine and Dentistry of FAHSD City Clinical Hospital #70
Moscow, RUS, Russian Federation, 111399
Moscow City Clinical Hospital # 13
Moscow, RUS, Russian Federation, 115280
SEI HPE Moscow Medical Academy IM Sechenov of Roszdrav Clinic of Endocrinology
Moscow, RUS, Russian Federation, 119435
SI Internal Affairs of Moscow- Clinical Hospital
Moscow, RUS, Russian Federation, 125299
RAAMS Endocrinology and Diabetology Department
Moscow, RUS, Russian Federation, 125315
NEI HPE Smolensk State Medical Academy of FAHSD RNHI Smolensk Regional Clinical Hospital
Smolensk, RUS, Russian Federation, 214018
St Petersburg NHI City Polytclinic #77 City Diabetological Center #4
St Petersburg, RUS, Russian Federation, 193012
Central Medical Sanitary Unit #122
St Petersburg, RUS, Russian Federation, 194291
Pavlov State Medical Univ of St Petersburg
St Petersburg, RUS, Russian Federation, 197022
MHI Clinical Hospital for Emergency Care na NV Soloviev
Yaroslavl, RUS, Russian Federation, 150003
MCHI Medical Sanitary Unit of Novo-Yaroslavsky Oil Refining Plant
Yaroslavl, RUS, Russian Federation, 150023
NHI Yaroslavl Regional Clinical Hospital
Yaroslavl, RUS, Russian Federation, 150062
NI Central Clinical Hospital of RAS
Moscow, Russian Federation, 117 593
City Clinical Hospital # 61
Moscow, Russian Federation, 119 048
Complejo Hospitalario Nuestra Senora de Valme
Sevilla, Andalucia, Spain, 41014
Hospital de Mataro
Mataro, Barcelona, Spain, 08304
Hospital del Mar (Cano)
Barcelona, Spain, 08003
Centro Médico Teknon
Barcelona, Spain, 08022
Hospital Universitario de la Princessa
Madrid, Spain, 28006
Hospital Ramon y Cajal
Madrid, Spain, 28034
Corporacion Sanitaria Parc Tauli Unidad de Endocrinologia
Sabadell, Spain, 08208
Complejo Hospitalario Virgen del Rocio
Sevilla, Spain, 41013
Hospital Virgen Macarena (policlinico) 2ª planta Servicio de Endocrinologia y Nutricion
Sevilla, Spain, 41071
United Kingdom
Birchwood Surgery
Letchworth, Herts, United Kingdom, SG6 4UB
Lister Hospital
Stevenage, Herts, United Kingdom, SG1 4AB
Guy's & St Thomas Hospital
London, United Kingdom, SE1 9RT
Yaxley Group Practice
Peterborough, United Kingdom, PE7 3JL
Sponsors and Collaborators
Mannkind Corporation

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Mannkind Corporation Identifier: NCT00309244     History of Changes
Other Study ID Numbers: MKC-TI-102
First Posted: March 31, 2006    Key Record Dates
Results First Posted: October 16, 2014
Last Update Posted: October 16, 2014
Last Verified: October 2014

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin degludec, insulin aspart drug combination
Insulin Glargine
Insulin Aspart
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Heparin Antagonists
Molecular Mechanisms of Pharmacological Action