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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Technosphere® Insulin; Drug: Technosphere Powder

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil, 90035
  • Sao Paulo, Brazil, 01244
• Russian Federation
  • Kemerovo, Russian Federation, 650066
  • Leningrad Region, Russian Federation
  • Moscow, Russian Federation, 143420
  • Moscow, Russian Federation, 119991
  • Moscow, Russian Federation, 129128
  • Moscow, Russian Federation, 117036
  • Moscow, Russian Federation, 119435
  • Moscow, Russian Federation, 105120
  • Moscow, Russian Federation, 121374
  • Petrozavodsk, Russian Federation, 185019
  • Smolensk, Russian Federation, 214018
  • St. Petersburg, Russian Federation, 194354
  • St. Petersburg, Russian Federation, 194044
  • St. Petersburg, Russian Federation, 198013
  • St. Petersburg, Russian Federation, 195257
  • St. Petersburg, Russian Federation, 196601
  • Yaroslavl, Russian Federation, 150003
  • Yaroslavl, Russian Federation, 150023
• Ukraine
  • Kiev, Ukraine, 04114
  • UKR
    • Kharkiv, UKR, Ukraine, 61070
    • Kiev, UKR, Ukraine, 04053
    • Kyiv, UKR, Ukraine, 02175
    • Odesa, UKR, Ukraine, 65039
    • Vinnytsya, UKR, Ukraine, 21010
• 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
  • 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
  • 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
  • Illinois
    • Chicago, Illinois, United States, 60607
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
  • Minnesota
    • Edina, Minnesota, United States, 55435
  • 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
  • Nebraska
    • Omaha, Nebraska, United States, 68114
    • Omaha, Nebraska, United States, 68131
  • New Jersey
    • Clifton, New Jersey, United States, 07012
    • Hackensack, New Jersey, United States, 07601
    • Paramus, New Jersey, United States, 07652
  • New York
    • Flushing, New York, United States, 11365
    • New Hyde, New York, United States, 11042
  • North Carolina
    • Greenville, North Carolina, United States, 27834
  • Ohio
    • Perrysburg, Ohio, United States, 43551
  • Oregon
    • Portland, Oregon, United States, 97239
  • South Carolina
    • Greer, South Carolina, United States, 29651
  • Tennessee
    • Memphis, Tennessee, United States, 38119
  • Texas
    • Arlington, Texas, United States, 76014
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75230
    • Houston, Texas, United States, 77095
    • San Antonio, Texas, United States, 78229
    • San Antonio, Texas, United States, 78249
  • Utah
    • Magna, Utah, United States, 84044
  • Washington
    • Renton, Washington, United States, 98057
    • Wenatchee, Washington, United States, 98801

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 in HbA1c	Efficacy as measured by change in glycated hemoglobin (HbA1c) at Week 24	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 Change From Baseline to Week 24	Forced Expiratory Volume in 1 second - change from baseline to week 24	Baseline to Week 24
Change in Body Weight From Baseline to Week 24	Change in body weight from Baseline to Week 24	Baseline to Week 24
Proportion of Responders Achieving HbA1c <= 7.0%	Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%	Week 24
Incidence of Total Hypoglycemia	Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.	Baseline to Week 24
Incidence of Severe Hypoglycemia	Severe Hypoglycemia defined as: Requiring 3rd party assistance.	Baseline to Week 24
Total Hypoglycemia Event Rate	Number of Hypoglycemic Events/Total Subject Exposure Time (in months)	Baseline to Week 24
Severe Hypoglycemia Event Rate	Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)	Baseline to Week 24
Proportion of Responders Achieving HbA1c <= 6.5%	Efficacy as measured in proportion of subjects achieving HbA1c < or = to 6.5% at Week 24	Week 24
FPG Change From Baseline to Week 24	Efficacy as measured by mean change in fasting plasma glucose (FPG)	Baseline to Week 24
Proportion of Subjects Requiring Rescue Therapy		Baseline to Week 24
Time to Rescue	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	Baseline to Week 24
Mean 7-point Glucose Baseline Values	Mean 7-point self-monitored glucose at baseline	Baseline
Mean 7-point Glucose Week 24 Values	Mean 7-point self-monitored blood glucose at Week 24	Week 24

Collaborators and Investigators

• Sponsor: Mannkind Corporation

Publications and helpful links

General Publications

• Rosenstock J, Franco D, Korpachev V, Shumel B, Ma Y, Baughman R, Amin N, McGill JB; Affinity 2 Study Group. Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naive Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents. Diabetes Care. 2015 Dec;38(12):2274-81. doi: 10.2337/dc15-0629. Epub 2015 Aug 7.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: October 7, 2011
• First Submitted That Met QC Criteria: October 12, 2011
• First Posted (Estimate): October 13, 2011

Study Record Updates

• Last Update Posted (Estimate): October 17, 2014
• Last Update Submitted That Met QC Criteria: October 9, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: MKC-TI-175; Affinity2