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

NCT00309244 | Completed Phase 3 Results

• 1 other identifier: MKC-TI-102
• Study Type: interventional
• Target: 677
• Locations: 10 countries
• Sites: 151

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.

Conditions

Diabetes Type 2

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in HbA1c to Week 52

  Baseline to Week 52

Secondary Outcomes (7)

• Change From Baseline in Weight to Week 52

  Baseline to Week 52

• Change From Baseline in Fasting Plasma Glucose to Week 52

  Baseline to Week 52

• Number of Subjects Achieving Week 52 HbA1c Levels Less Than or Equal to 7.0%

  Week 52

• Incidence of Total Hypoglycemia

  52 Weeks

• Incidence of Severe Hypoglycemia

  52 Weeks

Study Arms (2)

TI + Insulin glargine

EXPERIMENTAL

Technosphere® Insulin Inhalation Powder + insulin glargine

Drug: Technosphere® Insulin Inhalation Powder

BPR 70/30

ACTIVE COMPARATOR

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)

Interventions

Technosphere® Insulin Inhalation Powder DRUG

Inhalation, 15U/30U

TI + Insulin glargine

70% insulin aspart protamine suspension and 30% insulin aspart injection (rDNA origin) DRUG

BPR 70/30, which is a premix of intermediate acting and rapid acting insulin given sc

BPR 70/30

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (151)

Coastal Clinical Research Inc

Mobile, Alabama, 36608, United States

Location

Quality of Life Medical & Research Center

Tucson, Arizona, 85712, United States

Location

Southern Arizona VA Healthcare System

Tucson, Arizona, 85723, United States

Location

Tucson Clinical Research

Tucson, Arizona, 85741, United States

Location

International Clinical Research Network

Chula Vista, California, 91911, United States

Location

Saad Hijazi MD Inc

Fresno, California, 93710, United States

Location

Valley Research

Fresno, California, 93720, United States

Location

Diabetes/Lipid Management and Research Center

Huntington Beach, California, 92648, United States

Location

South Bay Clinical Research

Inglewood, California, 90301, United States

Location

Southern California Endocrine Center

Pasadena, California, 91105, United States

Location

Coastal Biomedical Research Inc

Santa Monica, California, 90404, United States

Location

Diabetes Research Center

Tustin, California, 92780, United States

Location

University of Miami Diabetes Research Institute

Miami, Florida, 33136, United States

Location

International Research Associates LLC

Miami, Florida, 33156, United States

Location

Laureate Clinical Research Group

Atlanta, Georgia, 30308, United States

Location

Atlanta Pharmaceutical Research Center

Dunwoody, Georgia, 30338, United States

Location

North Atlanta Endocrinology & Diabetes PC

Lawrenceville, Georgia, 30045, United States

Location

Atlanta Center for Clinical Research

Roswell, Georgia, 30075, United States

Location

John H Stoger Jr Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Clintell Inc

Skokie, Illinois, 60076, United States

Location

Clintell Inc (Ellyin)

Skokie, Illinois, 60077, United States

Location

Medical Research of Louisiana

Metairie, Louisiana, 70002, United States

Location

Joslin Diabetes Center University of Maryland Medicine

Baltimore, Maryland, 21201, United States

Location

James A Dicke MDPA

Towson, Maryland, 21204, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Michigan Institute of Medicine

Livonia, Michigan, 48152, United States

Location

KMED Research

Saint Clair Shores, Michigan, 48081, United States

Location

Radiant Research Inc (Minneapolis)

Edina, Minnesota, 55435, United States

Location

International Diabetes Center

Minneapolis, Minnesota, 55416, United States

Location

Center for Urologic Clinical Trials University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Amin Radparvar's Private Practice

City of Saint Peters, Missouri, 63376, United States

Location

MedEx Healthcare Research Inc

St Louis, Missouri, 63117, United States

Location

Billings Clinic Research Division

Billings, Montana, 59101, United States

Location

Montana Health Research Institute

Billings, Montana, 59102, United States

Location

Creighton Diabetes Center

Omaha, Nebraska, 68131, United States

Location

New Mexico Clinical Research & Osteoporosis Center

Albuquerque, New Mexico, 87106, United States

Location

University of New Mexico HCS

Albuquerque, New Mexico, 87131, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

North Shore Diabetes and Endocrine Associates

New Hyde Park, New York, 11042, United States

Location

Univeristy of Physicians Group Endocrine Division

Staten Island, New York, 10301, United States

Location

Sensenbrenner Primary Care

Charlotte, North Carolina, 28277, United States

Location

East Carolina University (Tanenberg)

Greenville, North Carolina, 27834, United States

Location

Physician's East PA

Greenville, North Carolina, 27834, United States

Location

Valley Medical Primary Care

Centerville, Ohio, 45459, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Providence Health Partners - Center of Clinical Research

Dayton, Ohio, 45439, United States

Location

Cleveland Clinic Health System

East Cleveland, Ohio, 44112, United States

Location

Wells Institute for Health Awareness

Kettering, Ohio, 45429, United States

Location

Oregon Medical Group Clinical Resesarch

Eugene, Oregon, 97401, United States

Location

Lane Medical Research Group

Eugene, Oregon, 97404, United States

Location

Portland Diabetes & Endocrinology Center

Portland, Oregon, 97210, United States

Location

New Hope Research of Oregon

Portland, Oregon, 97219, United States

Location

Covance CRU Inc.

Portland, Oregon, 97239, United States

Location

Pennsylvania Research Institute

Bensalem, Pennsylvania, 19020, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Upstate Pharmaceutical Research

Greenville, South Carolina, 29615, United States

Location

Southeastern Research Associates Inc

Taylors, South Carolina, 29687, United States

Location

AM Diabetes and Endocrinology Center

Bartlett, Tennessee, 38133, United States

Location

Memphis Internal Medicine PLLC

Memphis, Tennessee, 38119, United States

Location

The Endocrine Clinic

Memphis, Tennessee, 38119, United States

Location

Israel Hartman MD

Arlington, Texas, 76014, United States

Location

South Arlington Primary Care Assoc PA

Arlington, Texas, 76017, United States

Location

Dallas Diabetes & Endocrine Center

Dallas, Texas, 75230, United States

Location

North Texas Endocrine Center

Dallas, Texas, 75231, United States

Location

Radiant Research Dallas-North

Dallas, Texas, 75231, United States

Location

Baylor Endocrine Center

Dallas, Texas, 75246, United States

Location

Galenos Research

Dallas, Texas, 75251, United States

Location

Spuhler Medical Associates

Friendswood, Texas, 77546, United States

Location

Clinical Trial Network

Houston, Texas, 77074, United States

Location

Quality Assurance Research Center Inc

San Antonio, Texas, 78205, United States

Location

Covenant Clinic Research

San Antonio, Texas, 78229, United States

Location

Diabetes & Glandular Disease Research Assoc PA

San Antonio, Texas, 78229, United States

Location

SAM Clinical Research Center

San Antonio, Texas, 78229, United States

Location

Salt Lake Research

Salt Lake City, Utah, 84107, United States

Location

Sentara Medical Group

Norfolk, Virginia, 23502, United States

Location

Clinical Research Associates of Tidewater

Norfolk, Virginia, 23507, United States

Location

Larry D Stonesifer MD Inc PS

Federal Way, Washington, 98003, United States

Location

Rainier Clinical Research Center Inc

Renton, Washington, 98055, United States

Location

Cedar Research

Tacoma, Washington, 98405, United States

Location

Liberty Research Center

Tacoma, Washington, 98405, United States

Location

Hospital Interzonal de Agudos Pedro Fiorito

Avellaneda, Buenos Aires, B1870ARG, Argentina

Location

CITDEEM - Centro de Investigacion y Tratamiento En Diabetes y Enfermedades Endocrino-Metabolicas

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

FUNDAPRES/CIMel

Buenos Aires, B1824KAJ, Argentina

Location

Centro Endocrinologic Tiempo

Buenos Aires, C1117ABH, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1181ACH, Argentina

Location

Cons Asoc de Endocrinologia

Buenos Aires, C1425AGC, Argentina

Location

Centro Medico Dra De Salvo

Buenos Aires, C1426ABP, Argentina

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital Sao Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

CPClin-Centro de Pesquisas Clinicas

São Paulo, São Paulo, 01244-030, Brazil

Location

Universidade Estabual de Maringa

Maringa Parana, 87020-900, Brazil

Location

Nucleo de Medicina Integrada

Mogi das Cruzes, 08780-090, Brazil

Location

Instituto Estadual De Diabetes e Endocrinologia Luis Capriglione

Rio de Janeiro, 20211-340, Brazil

Location

Ccbr Brasil Centro de Analises e Pesquisas Clinicas Ltda

Rio de Janeiro, 22271-100, Brazil

Location

Hospital Guilherme Alvaro

Santos, 11045-904, Brazil

Location

Hospital do Rim e Hipertensao

São Paulo, 04025-011, Brazil

Location

Instituto da Saude e Bem Estar da Mulher

São Paulo, 04062-003, Brazil

Location

Blumenau Servicos Medicos S/C Ltda

São Paulo, 05302-001, Brazil

Location

Centro de Pesquisa Clinica e Medicina Avancada

São Paulo, 05437-010, Brazil

Location

Keele Medical Place

Downsview, Ontario, M3M 3E5, Canada

Location

Quest Clinical Trials

Markham, Ontario, L6B 1A1, Canada

Location

Lifestyle Metabolism Center

Oakville, Ontario, L6H 3P1, Canada

Location

Sarnia Institute of Clinical Research

Sarnia, Ontario, N7T 4X3, Canada

Location

Lifestyle Metabolism Center

Thornhill, Ontario, L4J 8L7, Canada

Location

Lifestyle Metabolism Center

Toronto, Ontario, M4R 2G4, Canada

Location

Hospital del Salvador

Santiago, Santiago Metropolitan, Chile

Location

Hospital Padre Alberto Hurtado

Santiago, Santiago Metropolitan, Chile

Location

Hospital Clinico Pontificia Universidad Catolica de Chile

Santiago, Chile

Location

Hospital San Borja ArriaranUniversidad de Chile

Santiago, Chile

Location

Instituto Mexicano de Investigacion

Mexico City, Durango, 06700, Mexico

Location

Hospital OCA

Monterrey, Nuevo Leon, MX, 64000, Mexico

Location

Hospital Universitario Dr Jose E Gonzalez

Monterrey, Nuevo León, 64460, Mexico

Location

Hospital Santa Engracia-CIMA

Garza García, 66260, Mexico

Location

Centro de Estudios en Diabetes

Mexico City, 01120, Mexico

Location

Cifbiotec

Mexico City, CP14050, Mexico

Location

Oddzial Chorob Wewnetrznych

Bialystock, POL, 15-950, Poland

Location

NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny

Bialystok, POL, 15-435, Poland

Location

Katedra I Klinika Chorob Metabolicznych Collegium Medicum Uniwersytety Jagiellonskiego

Krakow, POL, 31 501, Poland

Location

Klliniczny nr 1 im Norberta Barlickiego Uniwersytetu Medycznego w Lodzi

Lodz, POL, 90 153, Poland

Location

Instytut Centrum Zdrowia (009) Matki Polki

Lodz, POL, 93-338, Poland

Location

Szpital Kolejowy im Dr w Roeflera(009) Oddzial Gastorenterologii

Pruszków, POL, 05 800, Poland

Location

NZOZ Diabetologiczna Poradnia Specjalistyczna

Warsaw, 01-911, Poland

Location

NHI Kemerovo Regional Clinical Hospital

Kemerovo, RUS, 650061, Russia

Location

NI Principal Military Clinical Hospital n a academician N.N. Burdenko of the Ministry of Defense

Moscow, RUS, 105229, Russia

Location

NEI HPE Moscow State University of Medicine and Dentistry of FAHSD City Clinical Hospital #70

Moscow, RUS, 111399, Russia

Location

Moscow City Clinical Hospital # 13

Moscow, RUS, 115280, Russia

Location

SEI HPE Moscow Medical Academy IM Sechenov of Roszdrav Clinic of Endocrinology

Moscow, RUS, 119435, Russia

Location

SI Internal Affairs of Moscow- Clinical Hospital

Moscow, RUS, 125299, Russia

Location

RAAMS Endocrinology and Diabetology Department

Moscow, RUS, 125315, Russia

Location

St Petersburg NHI City Polytclinic #77 City Diabetological Center #4

Saint Petersburg, RUS, 193012, Russia

Location

Central Medical Sanitary Unit #122

Saint Petersburg, RUS, 194291, Russia

Location

Pavlov State Medical Univ of St Petersburg

Saint Petersburg, RUS, 197022, Russia

Location

NEI HPE Smolensk State Medical Academy of FAHSD RNHI Smolensk Regional Clinical Hospital

Smolensk, RUS, 214018, Russia

Location

MHI Clinical Hospital for Emergency Care na NV Soloviev

Yaroslavl, RUS, 150003, Russia

Location

MCHI Medical Sanitary Unit of Novo-Yaroslavsky Oil Refining Plant

Yaroslavl, RUS, 150023, Russia

Location

NHI Yaroslavl Regional Clinical Hospital

Yaroslavl, RUS, 150062, Russia

Location

NI Central Clinical Hospital of RAS

Moscow, 117 593, Russia

Location

City Clinical Hospital # 61

Moscow, 119 048, Russia

Location

Complejo Hospitalario Nuestra Senora de Valme

Seville, Andalusia, 41014, Spain

Location

Hospital de Mataro

Mataró, Barcelona, 08304, Spain

Location

Hospital del Mar (Cano)

Barcelona, 08003, Spain

Location

Centro Médico Teknon

Barcelona, 08022, Spain

Location

Hospital Universitario de la Princessa

Madrid, 28006, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Corporacion Sanitaria Parc Tauli Unidad de Endocrinologia

Sabadell, 08208, Spain

Location

Complejo Hospitalario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Virgen Macarena (policlinico) 2ª planta Servicio de Endocrinologia y Nutricion

Seville, 41071, Spain

Location

Birchwood Surgery

Letchworth Garden City, Herts, SG6 4UB, United Kingdom

Location

Lister Hospital

Stevenage, Herts, SG1 4AB, United Kingdom

Location

Guy's & St Thomas Hospital

London, SE1 9RT, United Kingdom

Location

Yaxley Group Practice

Peterborough, PE7 3JL, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 21999640 DERIVED

• 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.

  PMID: 20609970 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Aspart

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

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: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2006
• First Posted: March 31, 2006
• Study Start: February 1, 2006
• Primary Completion: August 1, 2008
• Study Completion: September 1, 2008
• Last Updated: October 16, 2014
• Results First Posted: October 16, 2014

Record last verified: 2014-10

Locations

CL (4); AR (7); ME (6); BR (12); US (80); ES (9); GB (4); RU (16); PL (7); CA (6)