Comparison of Technosphere® Insulin Versus Technosphere Powder (Placebo) in Insulin-Naive Subjects With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT01451398
First received: October 7, 2011
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

Insulin-naive subjects with Type 2 Diabetes Mellitus who are sub-optimally controlled on either maximum tolerated dose of metformin or maximum tolerated dose of metformin plus one or two other oral anti-diabetic medications will have either Prandial Technosphere® Insulin or Technosphere Powder (placebo) added to their oral antidiabetic drugs.


Condition Intervention Phase
Type 2 Diabetes
Drug: Technosphere® Insulin
Drug: Technosphere Powder
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized, Clinical Trial Evaluating the Efficacy and Safety of Prandial Technosphere® Insulin Inhalation Powder Versus Technosphere Inhalation Powder in Insulin Naïve Subjects With Type 2 Diabetes Mellitus Poorly Controlled With Oral Antidiabetic Agents Over a 24 Week Treatment Period

Resource links provided by NLM:


Further study details as provided by Mannkind Corporation:

Primary Outcome Measures:
  • Change From Baseline to Week 24 in HbA1c [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Efficacy as measured by change in glycated hemoglobin (HbA1c) at Week 24


Secondary Outcome Measures:
  • Proportion of Responders Achieving HbA1c <= 7.0% [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%

  • Proportion of Responders Achieving HbA1c <= 6.5% [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Efficacy as measured in proportion of subjects achieving HbA1c < or = to 6.5% at Week 24

  • FPG Change From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Efficacy as measured by mean change in fasting plasma glucose (FPG)

  • Proportion of Subjects Requiring Rescue Therapy [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Time to Rescue [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Time from Week 0 (baseline) to initiation of rescue therapy (up to a maximum of 24 weeks/end of treatment) for subjects not responding to treatment

  • FEV1 Change From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Forced Expiratory Volume in 1 second - change from baseline to week 24

  • Incidence of Total Hypoglycemia [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.

  • Incidence of Severe Hypoglycemia [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Severe Hypoglycemia defined as: Requiring 3rd party assistance.

  • Total Hypoglycemia Event Rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Number of Hypoglycemic Events/Total Subject Exposure Time (in months)

  • Severe Hypoglycemia Event Rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)

  • Mean 7-point Glucose Baseline Values [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Mean 7-point self-monitored glucose at baseline

  • Mean 7-point Glucose Week 24 Values [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Mean 7-point self-monitored blood glucose at Week 24

  • Change in Body Weight From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Change in body weight from Baseline to Week 24


Enrollment: 353
Study Start Date: November 2011
Study Completion Date: July 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TI inhalation powder
Technosphere® Insulin powder administered via the Gen2 inhaler added to 2 or more stable OADs
Drug: Technosphere® Insulin
Technosphere® Insulin Inhalation Powder
Placebo Comparator: Technosphere powder
Technosphere powder (with no insulin) administered via the Gen2 inhaler added to 2 or more stable OADs
Drug: Technosphere Powder
Placebo Comparator

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HbA1c > or = to 7.5% and < or = to 10.0%
  • Body mass index (BMI) < or = to 45 kg/m2
  • Non smoker for at least 6 months before Screening
  • Clinical diagnosis of type 2 diabetes mellitus for more than 12 months
  • Currently receiving as diabetes treatment only metformin or 2 or more OADs and on stable doses for at least 3 months before enrollment

    • Subjects receiving metformin must be on at least 1.5gm daily, or up to the maximum tolerated dose
    • Subjects treated with a sulfonylurea must be on at least 50% of the total maximum approved dose for a given agent
    • Subjects receiving a DPP-4 inhibitor must receive the maximum approved dose specific for that agent
    • Metiglinide and alpha-glucoside inhibitors must be taken at the highest tolerated dose within the approved dose range
  • No previous or current treatment with insulin, except during an acute illness, gestational diabetes, or at time of initial diagnosis of diabetes
  • Forced expiratory volume in one second (FEV1) > or = to 70% Third National Health and Nutrition Examination Survey (NHANES III) predicted
  • Forced vital capacity (FVC) > or = to 70% NHANES III predicted
  • Forced expiratory volume in one second as a percentage of forced vital capacity (FEV1/FVC) > or = to NHANES III lower limit of normal (LLN)

Exclusion Criteria:

  • History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, or any other clinically important pulmonary disease (eg, pulmonary fibrosis)
  • Any clinically significant radiological findings on screening chest x-ray
  • Use of medications for asthma, COPD, or any other chronic respiratory conditions
  • Evidence of serious complications of diabetes (proliferative retinopathy, autonomic neuropathy with symptoms of gastroparesis or cardiac arrhythmia; sensory neuropathy that makes manipulation of the Gen2C inhaler difficult)
  • Renal disease or renal dysfunction
  • Significant cardiovascular dysfunction or history thereof within 12 months of screening; serious arrhythmia, treatment with medications to control/treat arrhythmias; myocardial infarction; cardiac surgery; history of valvular heart disease
  • Previous or current use of amiodarone
  • Treatment with glucagon-like peptide-1 (GLP-1) analogs, thiazolidinediones (TZD), or weight loss drugs (eg, sibutramine, orlistat) within 3 months of screening
  • History of pulmonary embolism or deep venous thrombosis in the 12 months before Screening
  • History of recent blood transfusion (within previous 3 months) or diagnosis of hemoglobinopathies that may affect HbA1c measurements
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01451398

  Hide Study Locations
Locations
United States, California
Anaheim, California, United States, 92807
Huntington Beach, California, United States, 92648
Laguna Hills, California, United States, 92653
Long Beach, California, United States, 90806
Los Angeles, California, United States, 90036
Los Gatos, California, United States, 95032
Tustin, California, United States, 92780
West Hills, California, United States, 91307
United States, Florida
Hialeah, Florida, United States, 33012
Hollywood, Florida, United States, 33021
Miami, Florida, United States, 33173
Miami, Florida, United States, 33156
New Port Richey, Florida, United States, 34652
North Miami Beach, Florida, United States, 33179
Pembroke Pines, Florida, United States, 33026
Pinellas Park, Florida, United States, 33781
West Palm Beach, Florida, United States, 33401
United States, Georgia
Atlanta, Georgia, United States, 30308
Atlanta, Georgia, United States, 30318
Dunwoody, Georgia, United States, 30338
Lawrenceville, Georgia, United States, 30045
Roswell, Georgia, United States, 30076
United States, Illinois
Chicago, Illinois, United States, 60607
United States, Louisiana
Baton Rouge, Louisiana, United States, 70808
United States, Minnesota
Edina, Minnesota, United States, 55435
United States, Missouri
Jefferson City, Missouri, United States, 65109
St Peters, Missouri, United States, 63376
St. Louis, Missouri, United States, 63110
St. Louis, Missouri, United States, 63117
United States, Nebraska
Omaha, Nebraska, United States, 68131
Omaha, Nebraska, United States, 68114
United States, New Jersey
Clifton, New Jersey, United States, 07012
Hackensack, New Jersey, United States, 07601
Paramus, New Jersey, United States, 07652
United States, New York
Flushing, New York, United States, 11365
New Hyde, New York, United States, 11042
United States, North Carolina
Greenville, North Carolina, United States, 27834
United States, Ohio
Perrysburg, Ohio, United States, 43551
United States, Oregon
Portland, Oregon, United States, 97239
United States, South Carolina
Greer, South Carolina, United States, 29651
United States, Tennessee
Memphis, Tennessee, United States, 38119
United States, Texas
Arlington, Texas, United States, 76014
Dallas, Texas, United States, 75230
Dallas, Texas, United States, 75246
Houston, Texas, United States, 77095
San Antonio, Texas, United States, 78249
San Antonio, Texas, United States, 78229
United States, Utah
Magna, Utah, United States, 84044
United States, Washington
Renton, Washington, United States, 98057
Wenatchee, Washington, United States, 98801
Brazil
Porto Alegre, Brazil, 90035
Sao Paulo, Brazil, 01244
Russian Federation
Kemerovo, Russian Federation, 650066
Leningrad Region, Russian Federation
Moscow, Russian Federation, 119435
Moscow, Russian Federation, 129128
Moscow, Russian Federation, 105120
Moscow, Russian Federation, 121374
Moscow, Russian Federation, 119991
Moscow, Russian Federation, 143420
Moscow, Russian Federation, 117036
Petrozavodsk, Russian Federation, 185019
Smolensk, Russian Federation, 214018
St. Petersburg, Russian Federation, 195257
St. Petersburg, Russian Federation, 194044
St. Petersburg, Russian Federation, 194354
St. Petersburg, Russian Federation, 198013
St. Petersburg, Russian Federation, 196601
Yaroslavl, Russian Federation, 150003
Yaroslavl, Russian Federation, 150023
Ukraine
Kharkiv, UKR, Ukraine, 61070
Kiev, UKR, Ukraine, 04053
Kyiv, UKR, Ukraine, 02175
Odesa, UKR, Ukraine, 65039
Vinnytsya, UKR, Ukraine, 21010
Kiev, Ukraine, 04114
Sponsors and Collaborators
Mannkind Corporation
  More Information

No publications provided

Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT01451398     History of Changes
Other Study ID Numbers: MKC-TI-175, Affinity2
Study First Received: October 7, 2011
Results First Received: July 22, 2014
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014