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

Purpose

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.

Condition	Intervention	Phase
Type 1 Diabetes Mellitus	Drug: Technosphere Insulin Inhalation Powder Drug: Rapid Acting Analog	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Basic Science
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

Resource links provided by NLM:

Genetics Home Reference related topics: type 1 diabetes

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 1

Drug Information available for: Insulin human

U.S. FDA Resources

Further study details as provided by Mannkind Corporation:

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 [ Time Frame: Crossover 1 time within 3 - 10 days ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety variables including adverse events (AEs), clinical laboratory tests, vital signs and physical examinations [ Time Frame: Crossover 1 time within 3 - 10 days ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Enrollment:	17
Study Start Date:	March 2012
Study Completion Date:	January 2013
Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TI Inhalation Powder Technosphere Insulin Inhalation Powder using the Gen2C inhaler	Drug: Technosphere Insulin Inhalation Powder Inhalation Powder using the Gen2C inhaler Other Name: TI
Active Comparator: RAA Rapid Acting Analog	Drug: Rapid Acting Analog Subcutaneous Injection Other Name: RAA

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.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01544881

Locations

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

Sponsors and Collaborators

Mannkind Corporation

Investigators

Study Chair:

Chief Medical Officer

Mannkind Corporation

More Information

No publications provided

Responsible Party:	Mannkind Corporation
ClinicalTrials.gov Identifier:	NCT01544881 History of Changes
Other Study ID Numbers:	MKC-TI-177
Study First Received:	February 23, 2012
Last Updated:	January 24, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mannkind Corporation:

Pharmacokinetics
Pharmacodynamics
Hyperglycemia
Insulin

Additional relevant MeSH terms:

Respiratory Aspiration
Diabetes Mellitus
Diabetes Mellitus, Type 1
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Glucose Metabolism Disorders

Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 13, 2013