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Comparison of Technosphere Insulin Inhalation Powder & Subcutaneous Rapid-Acting Analog in Subjects With Type 1 Diabetes

Primary Purpose

Type 1 Diabetes Mellitus

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Technosphere Insulin Inhalation Powder
Rapid Acting Analog
Sponsored by
Mannkind Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 1 Diabetes Mellitus focused on measuring Pharmacokinetics, Pharmacodynamics, Hyperglycemia, Insulin

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Men and women aged 18 to 60 years
  • One of more daily sc insulin injections of any insulin type or insulin pump use
  • Body mass index (BMI) = 30 kg/m2

  • Pulmonary function tests (PFTs) conducted at Visit 1:

    • FEV1 ≥ 80% of the Third National Health and Nutrition Examination Survey (NHANES III) predicted
    • FVC ≥ 80% of the Third National Health and Nutrition Examination Survey (NHANES III) predicted
  • Diagnosis of type 1 diabetes for at least 12 months
  • Good venous access for blood draws
  • Written informed consent provided
  • No smoking in the previous 6 months (including cigarette, cigars, pipes) and negative urine cotinine testing (<100 ng/mL)
  • C-peptide < 0.3 ng/mL
  • Hemoglobin A1c (HbA1c) = 10.0%

Exclusion Criteria:

  • Total daily insulin requirement of = 1.4 U/kg body weight
  • Serum creatinine = 2.0 mg/dL in men and > 1.8 mg/dL in women
  • Blood donation of 500 mL within the previous 56 days
  • Current treatment with pramlintide acetate or exenatide
  • Unstable diabetes control and evidence of severe complications of diabetes (ie, autonomic neuropathy)
  • History of chronic obstructive pulmonary disease (COPD) or asthma, or any other clinically important pulmonary disease confirmed by pulmonary function testing or radiologic findings
  • Upper respiratory tract infection within 8 weeks before screening
  • History of coronary artery disease, peripheral vascular disease, or congestive heart failure
  • Allergy to study drug, food, or other study material (eg, peanuts, soy products)
  • Clinically significant active or chronic illness
  • History of drug or alcohol abuse
  • Positive urine drug screen
  • Clinically significant screening ECG, physical examination, laboratory test, or vital sign abnormality
  • Exposure to any other investigational drug or device within 30 days before treatment or within 90 days before treatment for drugs known to modify glucose metabolism (except metformin)
  • History of malignancy within the 5 years before screening (other than basal cell carcinoma)
  • History of human immunodeficiency virus (HIV) infection or hepatitis B or C
  • Women who are pregnant, lactating, or planning to become pregnant during the clinical study period
  • Women of childbearing potential (defined as premenopausal and not surgically sterilized or postmenopausal for fewer than 2 years) not practicing adequate birth control. Adequate birth control is defined as using oral, percutaneous, or transdermal contraceptives; condoms and diaphragms (double barrier) with a spermicide; or intrauterine devices. Postmenopausal for the purposes of this clinical study includes experiencing amenorrhea for 2 or more years or being surgically sterile
  • Inability, in the opinion of the PI or a designee, to adequately inhale TI Inhalation Powder
  • Any subject who, in the opinion of the PI or a designee, appears to not be qualified for this study

Sites / Locations

  • Profil Institute for Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TI Inhalation Powder

RAA

Arm Description

Technosphere Insulin Inhalation Powder using the Gen2C inhaler

Rapid Acting Analog

Outcomes

Primary Outcome Measures

PK measures for TI Inhalation Powder (20U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing
PK measures for RAA (8U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 and 360 minutes post-RAA dosing

Secondary Outcome Measures

Safety variables including adverse events (AEs), clinical laboratory tests, vital signs and physical examinations
Area under serum glucose infusion rate (GIR AUC 0-360) for TI Inhalation Powder (20U) as measured by: GIR AUC 0-360 timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing
Area under serum glucose infusion rate (GIR AUC 0-360) for RAA (8U) as measured by: GIR AUC 0-360 timepoints: 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 and 360 minutes post-RAA dosing

Full Information

First Posted
February 23, 2012
Last Updated
January 24, 2013
Sponsor
Mannkind Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01544881
Brief Title
Comparison of Technosphere Insulin Inhalation Powder & Subcutaneous Rapid-Acting Analog in Subjects With Type 1 Diabetes
Official Title
A Phase 1, Single-center, Open-label, Randomized, Crossover Design Clinical Study in Subjects With Type 1 Diabetes Comparing Insulin Exposure & Response Following Inhalation of Technosphere Insulin Inhalation Powder Using the Gen2C Inhaler Vs Subcutaneous Rapid-Acting Analog
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mannkind Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is an Open-label, randomized study in Type 1 diabetics looking at exposure and response (PK/PD) of TI using GEN2C Inhaler versus rapid acting analog.
Detailed Description
Subjects with Type 1 diabetes will be randomized to either one dose of TI inhaled using the Gen2C device, or one dose of subcutaneously injected Rapid Acting Analog (RAA) and crossed over. Crossover Sequences: Sequence #1: Period 1 - one 20 U cartridge of TI; Period 2 - 8 U of RAA Sequence #2: Period 1 - 8 U RAA; Period 2 - one 20 U cartridge of TI An euglycemic clamp procedure will be performed at each dosing visit. The purpose of this study is to characterize the pharmacokinetics (PK) of the one dose of TI Inhalation Powder using the Gen2C inhaler as compared to one dose of subcutaneous RAA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
Keywords
Pharmacokinetics, Pharmacodynamics, Hyperglycemia, Insulin

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TI Inhalation Powder
Arm Type
Experimental
Arm Description
Technosphere Insulin Inhalation Powder using the Gen2C inhaler
Arm Title
RAA
Arm Type
Active Comparator
Arm Description
Rapid Acting Analog
Intervention Type
Drug
Intervention Name(s)
Technosphere Insulin Inhalation Powder
Other Intervention Name(s)
TI
Intervention Description
Inhalation Powder using the Gen2C inhaler
Intervention Type
Drug
Intervention Name(s)
Rapid Acting Analog
Other Intervention Name(s)
RAA
Intervention Description
Subcutaneous Injection
Primary Outcome Measure Information:
Title
PK measures for TI Inhalation Powder (20U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing
Time Frame
Crossover 1 time within 3 - 10 days
Title
PK measures for RAA (8U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 and 360 minutes post-RAA dosing
Time Frame
Crossover 1 time within 3 - 10 days
Secondary Outcome Measure Information:
Title
Safety variables including adverse events (AEs), clinical laboratory tests, vital signs and physical examinations
Time Frame
Crossover 1 time within 3 - 10 days
Title
Area under serum glucose infusion rate (GIR AUC 0-360) for TI Inhalation Powder (20U) as measured by: GIR AUC 0-360 timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing
Time Frame
Crossover 1 time within 3 - 10 days
Title
Area under serum glucose infusion rate (GIR AUC 0-360) for RAA (8U) as measured by: GIR AUC 0-360 timepoints: 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 and 360 minutes post-RAA dosing
Time Frame
Crossover 1 time within 3 - 10 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women aged 18 to 60 years One of more daily sc insulin injections of any insulin type or insulin pump use Body mass index (BMI) = 30 kg/m2 Pulmonary function tests (PFTs) conducted at Visit 1: FEV1 ≥ 80% of the Third National Health and Nutrition Examination Survey (NHANES III) predicted FVC ≥ 80% of the Third National Health and Nutrition Examination Survey (NHANES III) predicted Diagnosis of type 1 diabetes for at least 12 months Good venous access for blood draws Written informed consent provided No smoking in the previous 6 months (including cigarette, cigars, pipes) and negative urine cotinine testing (<100 ng/mL) C-peptide < 0.3 ng/mL Hemoglobin A1c (HbA1c) = 10.0% Exclusion Criteria: Total daily insulin requirement of = 1.4 U/kg body weight Serum creatinine = 2.0 mg/dL in men and > 1.8 mg/dL in women Blood donation of 500 mL within the previous 56 days Current treatment with pramlintide acetate or exenatide Unstable diabetes control and evidence of severe complications of diabetes (ie, autonomic neuropathy) History of chronic obstructive pulmonary disease (COPD) or asthma, or any other clinically important pulmonary disease confirmed by pulmonary function testing or radiologic findings Upper respiratory tract infection within 8 weeks before screening History of coronary artery disease, peripheral vascular disease, or congestive heart failure Allergy to study drug, food, or other study material (eg, peanuts, soy products) Clinically significant active or chronic illness History of drug or alcohol abuse Positive urine drug screen Clinically significant screening ECG, physical examination, laboratory test, or vital sign abnormality Exposure to any other investigational drug or device within 30 days before treatment or within 90 days before treatment for drugs known to modify glucose metabolism (except metformin) History of malignancy within the 5 years before screening (other than basal cell carcinoma) History of human immunodeficiency virus (HIV) infection or hepatitis B or C Women who are pregnant, lactating, or planning to become pregnant during the clinical study period Women of childbearing potential (defined as premenopausal and not surgically sterilized or postmenopausal for fewer than 2 years) not practicing adequate birth control. Adequate birth control is defined as using oral, percutaneous, or transdermal contraceptives; condoms and diaphragms (double barrier) with a spermicide; or intrauterine devices. Postmenopausal for the purposes of this clinical study includes experiencing amenorrhea for 2 or more years or being surgically sterile Inability, in the opinion of the PI or a designee, to adequately inhale TI Inhalation Powder Any subject who, in the opinion of the PI or a designee, appears to not be qualified for this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Medical Officer
Organizational Affiliation
Mannkind Corporation
Official's Role
Study Chair
Facility Information:
Facility Name
Profil Institute for Clinical Research
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States

12. IPD Sharing Statement

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Comparison of Technosphere Insulin Inhalation Powder & Subcutaneous Rapid-Acting Analog in Subjects With Type 1 Diabetes

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