Clinical trial NCT00309244: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Type 2
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2006-03-31
Enrollment: 677
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in HbA1c to Week 52
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Change From Baseline in Weight to Week 52
timeFrame: Baseline to Week 52
measure: Change From Baseline in Fasting Plasma Glucose to Week 52
timeFrame: Baseline to Week 52
measure: Number of Subjects Achieving Week 52 HbA1c Levels Less Than or Equal to 7.0%
timeFrame: Week 52
measure: Incidence of Total Hypoglycemia
timeFrame: 52 Weeks
measure: Incidence of Severe Hypoglycemia
timeFrame: 52 Weeks
measure: Total Hypoglycemia Event Rate
timeFrame: 52 Weeks
measure: Severe Hypoglycemia Event Rate
timeFrame: 52 Weeks
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research Inc
state: Alabama
city: Tucson
country: United States
facility: Quality of Life Medical & Research Center
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Healthcare System
state: Arizona
city: Tucson
country: United States
facility: Tucson Clinical Research
state: Arizona
city: Chula Vista
country: United States
facility: International Clinical Research Network
state: California
city: Fresno
country: United States
facility: Saad Hijazi MD Inc
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Huntington Beach
country: United States
facility: Diabetes/Lipid Management and Research Center
state: California
city: Inglewood
country: United States
facility: South Bay Clinical Research
state: California
city: Pasadena
country: United States
facility: Southern California Endocrine Center
state: California
city: Santa Monica
country: United States
facility: Coastal Biomedical Research Inc
state: California
city: Tustin
country: United States
facility: Diabetes Research Center
state: California
city: Miami
country: United States
facility: University of Miami Diabetes Research Institute
state: Florida
city: Miami
country: United States
facility: International Research Associates LLC
state: Florida
city: Atlanta
country: United States
facility: Laureate Clinical Research Group
state: Georgia
city: Dunwoody
country: United States
facility: Atlanta Pharmaceutical Research Center
state: Georgia
city: Lawrenceville
country: United States
facility: North Atlanta Endocrinology & Diabetes PC
state: Georgia
city: Roswell
country: United States
facility: Atlanta Center for Clinical Research
state: Georgia
city: Chicago
country: United States
facility: John H Stoger Jr Hospital of Cook County
state: Illinois
city: Skokie
country: United States
facility: Clintell Inc
state: Illinois
city: Skokie
country: United States
facility: Clintell Inc (Ellyin)
state: Illinois
city: Metairie
country: United States
facility: Medical Research of Louisiana
state: Louisiana
city: Baltimore
country: United States
facility: Joslin Diabetes Center University of Maryland Medicine
state: Maryland
city: Towson
country: United States
facility: James A Dicke MDPA
state: Maryland
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Livonia
country: United States
facility: Michigan Institute of Medicine
state: Michigan
city: St Clair Shores
country: United States
facility: KMED Research
state: Michigan
city: Edina
country: United States
facility: Radiant Research Inc (Minneapolis)
state: Minnesota
city: Minneapolis
country: United States
facility: International Diabetes Center
state: Minnesota
city: Minneapolis
country: United States
facility: Center for Urologic Clinical Trials University of Minnesota
state: Minnesota
city: St Louis
country: United States
facility: MedEx Healthcare Research Inc
state: Missouri
city: St Peters
country: United States
facility: Amin Radparvar's Private Practice
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Research Division
state: Montana
city: Billings
country: United States
facility: Montana Health Research Institute
state: Montana
city: Omaha
country: United States
facility: Creighton Diabetes Center
state: Nebraska
city: Albuquerque
country: United States
facility: New Mexico Clinical Research & Osteoporosis Center
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico HCS
state: New Mexico
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
facility: North Shore Diabetes and Endocrine Associates
state: New York
city: Staten Island
country: United States
facility: Univeristy of Physicians Group Endocrine Division
state: New York
city: Charlotte
country: United States
facility: Sensenbrenner Primary Care
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University (Tanenberg)
state: North Carolina
city: Greenville
country: United States
facility: Physician's East PA
state: North Carolina
city: Centerville
country: United States
facility: Valley Medical Primary Care
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Dayton
country: United States
facility: Providence Health Partners - Center of Clinical Research
state: Ohio
city: East Cleveland
country: United States
facility: Cleveland Clinic Health System
state: Ohio
city: Kettering
country: United States
facility: Wells Institute for Health Awareness
state: Ohio
city: Eugene
country: United States
facility: Oregon Medical Group Clinical Resesarch
state: Oregon
city: Eugene
country: United States
facility: Lane Medical Research Group
state: Oregon
city: Portland
country: United States
facility: Portland Diabetes & Endocrinology Center
state: Oregon
city: Portland
country: United States
facility: New Hope Research of Oregon
state: Oregon
city: Portland
country: United States
facility: Covance CRU Inc.
state: Oregon
city: Bensalem
country: United States
facility: Pennsylvania Research Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Taylors
country: United States
facility: Southeastern Research Associates Inc
state: South Carolina
city: Bartlett
country: United States
facility: AM Diabetes and Endocrinology Center
state: Tennessee
city: Memphis
country: United States
facility: Memphis Internal Medicine PLLC
state: Tennessee
city: Memphis
country: United States
facility: The Endocrine Clinic
state: Tennessee
city: Arlington
country: United States
facility: Israel Hartman MD
state: Texas
city: Arlington
country: United States
facility: South Arlington Primary Care Assoc PA
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes & Endocrine Center
state: Texas
city: Dallas
country: United States
facility: North Texas Endocrine Center
state: Texas
city: Dallas
country: United States
facility: Radiant Research Dallas-North
state: Texas
city: Dallas
country: United States
facility: Baylor Endocrine Center
state: Texas
city: Dallas
country: United States
facility: Galenos Research
state: Texas
city: Friendswood
country: United States
facility: Spuhler Medical Associates
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: San Antonio
country: United States
facility: Quality Assurance Research Center Inc
state: Texas
city: San Antonio
country: United States
facility: Covenant Clinic Research
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Research Assoc PA
state: Texas
city: San Antonio
country: United States
facility: SAM Clinical Research Center
state: Texas
city: Salt Lake City
country: United States
facility: Salt Lake Research
state: Utah
city: Norfolk
country: United States
facility: Sentara Medical Group
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Federal Way
country: United States
facility: Larry D Stonesifer MD Inc PS
state: Washington
city: Renton
country: United States
facility: Rainier Clinical Research Center Inc
state: Washington
city: Tacoma
country: United States
facility: Cedar Research
state: Washington
city: Tacoma
country: United States
facility: Liberty Research Center
state: Washington
city: Avellaneda
country: Argentina
facility: Hospital Interzonal de Agudos Pedro Fiorito
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: CITDEEM - Centro de Investigacion y Tratamiento En Diabetes y Enfermedades Endocrino-Metabolicas
state: Tucuman
city: Buenos Aires
country: Argentina
facility: FUNDAPRES/CIMel
city: Buenos Aires
country: Argentina
facility: Centro Endocrinologic Tiempo
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Cons Asoc de Endocrinologia
city: Buenos Aires
country: Argentina
facility: Centro Medico Dra De Salvo
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
state: Rio Grande do Sul
city: Maringa Parana
country: Brazil
facility: Universidade Estabual de Maringa
city: Mogi das Cruzes
country: Brazil
facility: Nucleo de Medicina Integrada
city: Rio de Janeiro
country: Brazil
facility: Instituto Estadual De Diabetes e Endocrinologia Luis Capriglione
city: Rio de Janeiro
country: Brazil
facility: Ccbr Brasil Centro de Analises e Pesquisas Clinicas Ltda
city: Santos
country: Brazil
facility: Hospital Guilherme Alvaro
city: Sao Paulo
country: Brazil
facility: CPClin-Centro de Pesquisas Clinicas
city: Sao Paulo
country: Brazil
facility: Hospital do Rim e Hipertensao
city: Sao Paulo
country: Brazil
facility: Instituto da Saude e Bem Estar da Mulher
city: Sao Paulo
country: Brazil
facility: Blumenau Servicos Medicos S/C Ltda
city: Sao Paulo
country: Brazil
facility: Centro de Pesquisa Clinica e Medicina Avancada
city: Downsview
country: Canada
facility: Keele Medical Place
state: Ontario
city: Markham
country: Canada
facility: Quest Clinical Trials
state: Ontario
city: Oakville
country: Canada
facility: Lifestyle Metabolism Center
state: Ontario
city: Sarnia
country: Canada
facility: Sarnia Institute of Clinical Research
state: Ontario
city: Thornhill
country: Canada
facility: Lifestyle Metabolism Center
state: Ontario
city: Toronto
country: Canada
facility: Lifestyle Metabolism Center
state: Ontario
city: Santiago
country: Chile
facility: Hospital del Salvador
state: Region Metropolitana
city: Santiago
country: Chile
facility: Hospital Padre Alberto Hurtado
state: Region Metropolitana
city: Santiago
country: Chile
facility: Hospital Clinico Pontificia Universidad Catolica de Chile
city: Santiago
country: Chile
facility: Hospital San Borja ArriaranUniversidad de Chile
city: Mexico City
country: Mexico
facility: Instituto Mexicano de Investigacion
state: Durango
city: Monterrey, Nuevo Leon
country: Mexico
facility: Hospital OCA
state: MX
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose E Gonzalez
state: Nuevo Leon
city: Garza Garcia
country: Mexico
facility: Hospital Santa Engracia-CIMA
city: Mexico City
country: Mexico
facility: Centro de Estudios en Diabetes
city: Mexico City
country: Mexico
facility: Cifbiotec
city: Bialystock
country: Poland
facility: Oddzial Chorob Wewnetrznych
state: POL
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny
state: POL
city: Krakow
country: Poland
facility: Katedra I Klinika Chorob Metabolicznych Collegium Medicum Uniwersytety Jagiellonskiego
state: POL
city: Lodz
country: Poland
facility: Klliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
state: POL
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia (009) Matki Polki
state: POL
city: Pruszkow
country: Poland
facility: Szpital Kolejowy im Dr w Roeflera(009) Oddzial Gastorenterologii
state: POL
city: Warszawa
country: Poland
facility: NZOZ Diabetologiczna Poradnia Specjalistyczna
city: Kemerovo
country: Russian Federation
facility: NHI Kemerovo Regional Clinical Hospital
state: RUS
city: Moscow
country: Russian Federation
facility: NI Principal Military Clinical Hospital n a academician N.N. Burdenko of the Ministry of Defense
state: RUS
city: Moscow
country: Russian Federation
facility: NEI HPE Moscow State University of Medicine and Dentistry of FAHSD City Clinical Hospital #70
state: RUS
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital # 13
state: RUS
city: Moscow
country: Russian Federation
facility: SEI HPE Moscow Medical Academy IM Sechenov of Roszdrav Clinic of Endocrinology
state: RUS
city: Moscow
country: Russian Federation
facility: SI Internal Affairs of Moscow- Clinical Hospital
state: RUS
city: Moscow
country: Russian Federation
facility: RAAMS Endocrinology and Diabetology Department
state: RUS
city: Smolensk
country: Russian Federation
facility: NEI HPE Smolensk State Medical Academy of FAHSD RNHI Smolensk Regional Clinical Hospital
state: RUS
city: St Petersburg
country: Russian Federation
facility: St Petersburg NHI City Polytclinic #77 City Diabetological Center #4
state: RUS
city: St Petersburg
country: Russian Federation
facility: Central Medical Sanitary Unit #122
state: RUS
city: St Petersburg
country: Russian Federation
facility: Pavlov State Medical Univ of St Petersburg
state: RUS
city: Yaroslavl
country: Russian Federation
facility: MHI Clinical Hospital for Emergency Care na NV Soloviev
state: RUS
city: Yaroslavl
country: Russian Federation
facility: MCHI Medical Sanitary Unit of Novo-Yaroslavsky Oil Refining Plant
state: RUS
city: Yaroslavl
country: Russian Federation
facility: NHI Yaroslavl Regional Clinical Hospital
state: RUS
city: Moscow
country: Russian Federation
facility: NI Central Clinical Hospital of RAS
city: Moscow
country: Russian Federation
facility: City Clinical Hospital # 61
city: Sevilla
country: Spain
facility: Complejo Hospitalario Nuestra Senora de Valme
state: Andalucia
city: Mataro
country: Spain
facility: Hospital de Mataro
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar (Cano)
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Madrid
country: Spain
facility: Hospital Universitario de la Princessa
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Sabadell
country: Spain
facility: Corporacion Sanitaria Parc Tauli Unidad de Endocrinologia
city: Sevilla
country: Spain
facility: Complejo Hospitalario Virgen del Rocio
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena (policlinico) 2ª planta Servicio de Endocrinologia y Nutricion
city: Letchworth
country: United Kingdom
facility: Birchwood Surgery
state: Herts
city: Stevenage
country: United Kingdom
facility: Lister Hospital
state: Herts
city: London
country: United Kingdom
facility: Guy's & St Thomas Hospital
city: Peterborough
country: United Kingdom
facility: Yaxley Group Practice
Study officials:
References:
citation: Peyrot M, Rubin RR. Patient-reported outcomes in adults with type 2 diabetes using mealtime inhaled technosphere insulin and basal insulin versus premixed insulin. Diabetes Technol Ther. 2011 Dec;13(12):1201-6. doi: 10.1089/dia.2011.0037. Epub 2011 Oct 14.
citation: Rosenstock J, Lorber DL, Gnudi L, Howard CP, Bilheimer DW, Chang PC, Petrucci RE, Boss AH, Richardson PC. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial. Lancet. 2010 Jun 26;375(9733):2244-53. doi: 10.1016/S0140-6736(10)60632-0.