Clinical trial NCT01490762: Healthy Normal Volunteers Looking at Exposure and Effects of Multiple Doses of Technosphere® Insulin (TI) Using the Gen2C Inhaler
Official title: A Phase 1, Open-label, Randomized, Crossover Design Clinical Trial in Healthy Normal Volunteers to Evaluate Insulin Exposure and Effect Following Inhalation of Technosphere® Insulin Inhalation Powder at Multiple Doses Using the Gen2C Inhaler
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: PK
PD
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2011-12-13
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is an open-Label, Randomized Study in Healthy Normal Volunteers looking at exposure and effects (PK/PD) of multiple doses of Technosphere® Insulin (TI) using the Gen2C inhaler.

Detailed description: Healthy Normal Volunteers will be randomized to a sequence of 4 different doses of Technosphere® Insulin (TI), inhaled using the Gen2C device, and one dose of subcutaneously injected Regular Human Insulin. A euglycemic clamp procedure will be performed at each dosing visit. The purpose of this study is to determine the insulin dose proportionality/linearity of Technosphere® Insulin (TI) Inhalation Powder based on the AUCo-180 after administration of the following doses using the Gen2C inhaler:

* 10 U (one 10 U cartridge)
* 30 U (one 10 U and one 20 U cartridge)
* 60 U (three 20 U cartridges)
* 80 U (four 20 U cartridges)

Eligibility criteria: Inclusion Criteria:

* Men and women aged 18 to 55 years who are considered healthy based on screening physical examination, medical history, clinical chemistry, and urinalysis
* Good venous access for blood draws
* No smoking in the previous 6 months (including cigarettes, cigars, pipes) and negative urine cotinine testing (\< 100 ng/mL)
* Body mass index (BMI) \< 32 kg/m2
* 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
* Written informed consent provided

Exclusion Criteria:

* Blood donation of 500 mL within the previous 56 days
* Fasting blood sugar \>130 mg/dL
* 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 asthma, COPD, or any other clinically relevant chronic lung disease
* Respiratory tract infection within 4 weeks before screening
* Donation of blood within 3 months before screening
* History of drug or alcohol abuse
* Positive urine drug screen
* Clinically significant screening ECG, physical examination, laboratory test, or vital sign abnormality
* Any subject who, in the opinion of the PI or a designee, appears to not be qualified for this study
* 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
* Any subject who at Visit 2 has a blood glucose value = 150 mg/dL 2 hours after the meal, should be discussed with the MKC medical monitor and may be removed as potentially having impaired glucose tolerance
* Inability, in the opinion of the PI or a designee, to adequately inhale TI Inhalation Powder
* 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

Primary outcomes:
measure: area-under-the-serum insulin concentration versus time curve (AUC0-240min) for inhaled Technosphere Insulin (TI) post-dosing of a TI dose (10 U, 30 U, 60 U or 80U). Time points: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180 and 240 minutes post-TI dosing
timeFrame: crossover 4 times over the course of up to 5 weeks
Secondary outcomes:
measure: Area-under-the-serum insulin concentration versus time curve (AUC0-240min) for inhaled Technosphere Insulin (TI) compared to that of subcutaneous regular human insulin (RHI)
timeFrame: crossover 5 times over the course of up to 6 weeks
measure: Area-under-the-serum glucose infusion rate (GIR AUC0-240min) for TI compared to AUC0-600min for RHI
timeFrame: crossover 5 times over the course of up to 6 weeks
measure: Safety variables included adverse events (AEs), clinical laboratory tests, vital signs and physical examinations
timeFrame: crossover 5 times for up to 6 weeks
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research
state: California
Study officials:
affiliation: Mannkind Corporation
name: Chief Medical Officer
role: STUDY_CHAIR
References: