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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Phase 2, Single-Center, Open-Label, Pharmacodynamic Clinical Trial to Evaluate the Effect of Technosphere® Insulin Inhalation Powder Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder) Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder) on Postprandial Glucose Levels in Subjects With Type 1 and Type 2 Diabetes Mellitus Ingesting Meals With Varied Carbohydrate Content

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00747006
• Other study ID #: MKC-TI-119
• Status: Terminated
• Phase: Phase 2
• First received: September 3, 2008
• Last updated: October 21, 2014
• Start date: September 2008
• Est. completion date: May 2011

Study information

• Verified date: October 2014
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: May 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2

Intervention

Drug:
• TI Inhalation Powder and Humalog (Amendment 1)
Subcutaneous (sc) rapid acting analog to be administered at one half of the meal challenge visits 15 minutes before a meal. Only the last 5 - 10 patients (Type 2) will be undergoing this amendment to the protocol.
• TI Inhalation Powder (original protocol)
Inhaled insulin technology to be administered immediately before a meal (prandially) for glucose control in Type 1 or Type 2 diabetics

Locations

Country	Name	City	State
United States	Sansum Medical Research Institute	Santa Barbara	California

Sponsors (1)

Lead Sponsor	Collaborator
Mannkind Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects)	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	0 to 240 minutes	No
Primary	Breakfast Plasma Glucose Time 0 Corrected AUC(0-240) - Original Protocol (TI Treated Type 1 Subjects)	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	0 to 240 minutes	No
Primary	Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)	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	0 to 240 minutes	No
Primary	Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)	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	0 to 240 minutes	No
Primary	Lunch Plasma Glucose Excursion - Original Protocol (TI Treated Type 1 Subjects)	Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at lunch	0 to 240 minutes	No
Primary	Breakfast Plasma Glucose Excursion - Original Protocol (TI Treated - Type 1 Subjects)	Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at breakfast	0 to 240 minutes	No
Primary	Lunch Plasma Glucose Excursion - Amendment 1 ( TI Treated Type 2 Subjects)	Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch	0 to 240 minutes	No
Primary	Lunch Plasma Glucose Excursion - Amendment 1 (Humalog Treated Type 2 Subjects)	Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch	0 to 240 minutes	No
Secondary	Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects)	Area over the plasma glucose - time curve from time 0 (immediately before starting lunch) to 240 minutes after the start of the lunch	0 to 240 minutes	No
Secondary	Breakfast Plasma Glucose AOC(0-240) - Original Protocol (TI Treated Type 1 Subjects)	Breakfast area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of breakfast	0 to 240 minutes	No
Secondary	Lunch Plasma Glucose AOC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)	Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch	0 to 240 minutes	No
Secondary	Lunch Plasma Glucose AOC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)	Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch	0 to 240 minutes	No