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Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder)When an Optimal Dose is Taken With Varied Carbohydrate Intake

Phase 2
Terminated
Conditions
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Interventions
Drug: TI Inhalation Powder (original protocol)
Drug: TI Inhalation Powder and Humalog (Amendment 1)
Registration Number
NCT00747006
Lead Sponsor
Mannkind Corporation
Brief Summary

The purpose of this study is to determine if, once a favorable dose of TI Inhalation Powder is established for either a type 1 or 2 patient, based on a average diabetic meal, the patient's favorable dose can be used safely, regardless of change in meal carbohydrate content. Patients were randomly assigned to various carbohydrate loads (0%, 50%, 100%, 150% or 200%). The 100% carbohydrate load was determined based upon their standard insulin dose for their normal meal.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
18
Inclusion Criteria
  • Clinical diagnoses of type 1 or type 2 diabetes mellitus
  • Fasting Plasma Glucose (FPG) 80, 140 mg/dL and glycated hemoglobin (A1C) > 6.5% and < or = 10.0%.
  • Body mass index (BMI) of < or = 40 kg/m2
  • Non-smokers (never smoked or former smokers [= 6 months since cessation]) and a urine cotinine level < or = 100 ng/dL
  • Forced expiratory volume in 1 second (FEV1) = 70% Third National Health and Nutrition Examination Survey (NHANES III) Predicted; pre-bronchodilator FEV1 as a percentage of forced vital capacity (FEV1/Forced vital capacity(FVC)) = 70%
  • For subjects with type 2 diabetes mellitus: Currently receiving oral diabetic treatment or basal insulin +/- oral diabetic treatment
Exclusion Criteria
  • History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, and/or any other clinically important pulmonary disease confirmed by pulmonary function test (PFT) and/or radiologic findings
  • Elevated liver function test (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times the normal reference range or bilirubin > 1.5 times the reference range)
  • Previous use of Exubera; use of Symlin (pramlintide acetate) and/or Byetta (exenatide) within the past 12 weeks
  • Unstable diabetes control and evidence of severe complications of diabetes mellitus (ie, autonomic neuropathy)
  • Exposure to any investigational product(s) in the past 12 weeks
  • For subjects with type 2 diabetes mellitus: In subjects taking metformin, serum creatinine > 1.4 mg/dL in female subjects and > 1.5 mg/dL in male subjects

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TI Inhalation Powder (original protocol)TI Inhalation Powder (original protocol)Under the original protocol, subjects with Type 1 and Type 2 diabetes will have TI Inhalation Powder administered prandially during dose optimization visits and meal challenge visits (with meals of varying carbohydrate contents). Subjects with Type 2 diabetes will also use TI Inhalation Powder daily at each meal between visits.
TI Inhalation Powder and Humalog (Amendment 1)TI Inhalation Powder and Humalog (Amendment 1)Under Amendment 1, TI Inhalation Powder will be administered prandially to a new subset of subjects with Type 2 diabetes during TI dose optimization visits and TI meal challenge visits (with meals of varying carbohydrate contents). Subjects will be crossed over to administration of Humalog 15 minutes before meals during Humalog dose optimization visits and Humalog meal challenge visits (with meals of varying carbohydrate contents). Subjects will also use TI Inhalation Powder daily at each meal between visits.
Primary Outcome Measures
NameTimeMethod
Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)0 to 240 minutes

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value.

AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value.

TIme 0 corrected AUC (0-240) = AUC - AOC

Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects)0 to 240 minutes

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value.

AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value.

TIme 0 corrected AUC (0-240) = AUC - AOC

Breakfast Plasma Glucose Time 0 Corrected AUC(0-240) - Original Protocol (TI Treated Type 1 Subjects)0 to 240 minutes

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value.

AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value.

TIme 0 corrected AUC (0-240) = AUC - AOC

Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)0 to 240 minutes

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value.

AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value.

TIme 0 corrected AUC (0-240) = AUC - AOC

Lunch Plasma Glucose Excursion - Original Protocol (TI Treated Type 1 Subjects)0 to 240 minutes

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at lunch

Breakfast Plasma Glucose Excursion - Original Protocol (TI Treated - Type 1 Subjects)0 to 240 minutes

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at breakfast

Lunch Plasma Glucose Excursion - Amendment 1 ( TI Treated Type 2 Subjects)0 to 240 minutes

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch

Lunch Plasma Glucose Excursion - Amendment 1 (Humalog Treated Type 2 Subjects)0 to 240 minutes

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch

Secondary Outcome Measures
NameTimeMethod
Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects)0 to 240 minutes

Area over the plasma glucose - time curve from time 0 (immediately before starting lunch) to 240 minutes after the start of the lunch

Breakfast Plasma Glucose AOC(0-240) - Original Protocol (TI Treated Type 1 Subjects)0 to 240 minutes

Breakfast area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of breakfast

Lunch Plasma Glucose AOC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)0 to 240 minutes

Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch

Lunch Plasma Glucose AOC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)0 to 240 minutes

Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch

Trial Locations

Locations (1)

Sansum Medical Research Institute

🇺🇸

Santa Barbara, California, United States

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