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

This study has been terminated.
(Business reasons)
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT00747006
First received: September 3, 2008
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Diabetes Mellitus, Type 1
Drug: TI Inhalation Powder and Humalog (Amendment 1)
Drug: TI Inhalation Powder (original protocol)
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Mannkind Corporation:

Primary Outcome Measures:
  • Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]

    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]

    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 (TI Treated Type 2 Subjects) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]

    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]

    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch


Secondary Outcome Measures:
  • Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 to 240 minutes ] [ Designated as safety issue: No ]
    Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch


Enrollment: 18
Study Start Date: September 2008
Study Completion Date: May 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00747006

Locations
United States, California
Sansum Medical Research Institute
Santa Barbara, California, United States, 93105
Sponsors and Collaborators
Mannkind Corporation
  More Information

No publications provided

Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT00747006     History of Changes
Other Study ID Numbers: MKC-TI-119
Study First Received: September 3, 2008
Results First Received: July 22, 2014
Last Updated: October 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Respiratory Aspiration
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Insulin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014