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

Phase 1
Completed
Conditions
Type 1 Diabetes Mellitus
Interventions
Drug: Technosphere Insulin Inhalation Powder
Drug: Rapid Acting Analog
Registration Number
NCT01544881
Lead Sponsor
Mannkind Corporation
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
17
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
TI Inhalation PowderTechnosphere Insulin Inhalation PowderTechnosphere Insulin Inhalation Powder using the Gen2C inhaler
RAARapid Acting AnalogRapid Acting Analog
Primary Outcome Measures
NameTimeMethod
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 dosingCrossover 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 dosingCrossover 1 time within 3 - 10 days
Secondary Outcome Measures
NameTimeMethod
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 dosingCrossover 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 dosingCrossover 1 time within 3 - 10 days
Safety variables including adverse events (AEs), clinical laboratory tests, vital signs and physical examinationsCrossover 1 time within 3 - 10 days

Trial Locations

Locations (1)

Profil Institute for Clinical Research

🇺🇸

Chula Vista, California, United States

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