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

Phase 3

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: Technosphere® Insulin; Drug: Technosphere Powder

• Registration Number: NCT01451398
• Lead Sponsor: Mannkind Corporation

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-10-07
• Study First Submitted QC: 2011-10-12
• Study First Posted: 2011-10-13
• Study Start: 2011-11
• Primary Completion: 2013-06
• Study Completion: 2013-07
• Disposition First Submitted: 2013-08-19
• Disposition First Submitted QC: 2013-08-19
• Disposition First Posted: 2013-08-27
• Results First Submitted: 2014-07-22
• Status Verified: 2014-10
• Results First Submitted QC: 2014-10-09
• Last Update Submitted: 2014-10-09
• Results First Posted: 2014-10-17
• Last Update Posted: 2014-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 353

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TI inhalation powder	Technosphere® Insulin	Technosphere® Insulin powder administered via the Gen2 inhaler added to 2 or more stable OADs
Technosphere powder	Technosphere Powder	Technosphere powder (with no insulin) administered via the Gen2 inhaler added to 2 or more stable OADs

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 24 in HbA1c	Baseline to Week 24	Efficacy as measured by change in glycated hemoglobin (HbA1c) at Week 24

Secondary Outcome Measures

Name	Time	Method
Total Hypoglycemia Event Rate	Baseline to Week 24	Number of Hypoglycemic Events/Total Subject Exposure Time (in months)
Mean 7-point Glucose Baseline Values	Baseline	Mean 7-point self-monitored glucose at baseline
Proportion of Responders Achieving HbA1c <= 6.5%	Week 24	Efficacy as measured in proportion of subjects achieving HbA1c \< or = to 6.5% at Week 24
FPG Change From Baseline to Week 24	Baseline to Week 24	Efficacy as measured by mean change in fasting plasma glucose (FPG)
Time to Rescue	Baseline to Week 24	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
Severe Hypoglycemia Event Rate	Baseline to Week 24	Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)
Change in Body Weight From Baseline to Week 24	Baseline to Week 24	Change in body weight from Baseline to Week 24
FEV1 Change From Baseline to Week 24	Baseline to Week 24	Forced Expiratory Volume in 1 second - change from baseline to week 24
Proportion of Responders Achieving HbA1c <= 7.0%	Week 24	Efficacy as measured in proportion of subjects achieving HbA1c \< or = to 7.0%
Proportion of Subjects Requiring Rescue Therapy	Baseline to Week 24
Mean 7-point Glucose Week 24 Values	Week 24	Mean 7-point self-monitored blood glucose at Week 24
Incidence of Total Hypoglycemia	Baseline to Week 24	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	Baseline to Week 24	Severe Hypoglycemia defined as: Requiring 3rd party assistance.