Clinical trial NCT01451398: Comparison of Technosphere® Insulin Versus Technosphere Powder (Placebo) in Insulin-Naive Subjects With Type 2 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2011-10-13
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline to Week 24 in HbA1c
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Proportion of Responders Achieving HbA1c <= 7.0%
timeFrame: Week 24
measure: Proportion of Responders Achieving HbA1c <= 6.5%
timeFrame: Week 24
measure: FPG Change From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Proportion of Subjects Requiring Rescue Therapy
timeFrame: Baseline to Week 24
measure: Time to Rescue
timeFrame: Baseline to Week 24
measure: FEV1 Change From Baseline to Week 24
timeFrame: Baseline to Week 24
measure: Incidence of Total Hypoglycemia
timeFrame: Baseline to Week 24
measure: Incidence of Severe Hypoglycemia
timeFrame: Baseline to Week 24
measure: Total Hypoglycemia Event Rate
timeFrame: Baseline to Week 24
measure: Severe Hypoglycemia Event Rate
timeFrame: Baseline to Week 24
measure: Mean 7-point Glucose Baseline Values
timeFrame: Baseline
measure: Mean 7-point Glucose Week 24 Values
timeFrame: Week 24
measure: Change in Body Weight From Baseline to Week 24
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Anaheim
country: United States
state: California
city: Huntington Beach
country: United States
state: California
city: Laguna Hills
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Gatos
country: United States
state: California
city: Tustin
country: United States
state: California
city: West Hills
country: United States
state: California
city: Hialeah
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: North Miami Beach
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Dunwoody
country: United States
state: Georgia
city: Lawrenceville
country: United States
state: Georgia
city: Roswell
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Baton Rouge
country: United States
state: Louisiana
city: Edina
country: United States
state: Minnesota
city: Jefferson City
country: United States
state: Missouri
city: St Peters
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Clifton
country: United States
state: New Jersey
city: Hackensack
country: United States
state: New Jersey
city: Paramus
country: United States
state: New Jersey
city: Flushing
country: United States
state: New York
city: New Hyde
country: United States
state: New York
city: Greenville
country: United States
state: North Carolina
city: Perrysburg
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Greer
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Magna
country: United States
state: Utah
city: Renton
country: United States
state: Washington
city: Wenatchee
country: United States
state: Washington
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
city: Kemerovo
country: Russian Federation
city: Leningrad Region
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Kharkiv
country: Ukraine
state: UKR
city: Kiev
country: Ukraine
state: UKR
city: Kyiv
country: Ukraine
state: UKR
city: Odesa
country: Ukraine
state: UKR
city: Vinnytsya
country: Ukraine
state: UKR
city: Kiev
country: Ukraine
Study officials:
References:
citation: 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.