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

January 24, 2013 updated by: Mannkind Corporation

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Chula Vista, California, United States, 91911
        • Profil Institute for Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TI Inhalation Powder
Technosphere Insulin Inhalation Powder using the Gen2C inhaler
Inhalation Powder using the Gen2C inhaler
Other Names:
  • TI
Active Comparator: RAA
Rapid Acting Analog
Subcutaneous Injection
Other Names:
  • RAA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Crossover 1 time within 3 - 10 days
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
Crossover 1 time within 3 - 10 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety variables including adverse events (AEs), clinical laboratory tests, vital signs and physical examinations
Time Frame: Crossover 1 time within 3 - 10 days
Crossover 1 time within 3 - 10 days
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
Crossover 1 time within 3 - 10 days
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
Crossover 1 time within 3 - 10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Chief Medical Officer, Mannkind Corporation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

February 23, 2012

First Submitted That Met QC Criteria

February 29, 2012

First Posted (Estimate)

March 6, 2012

Study Record Updates

Last Update Posted (Estimate)

January 25, 2013

Last Update Submitted That Met QC Criteria

January 24, 2013

Last Verified

January 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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