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

  Show 76 Study Locations
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
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014