Healthy Normal Volunteers Looking at Exposure and Effects of Multiple Doses of Technosphere® Insulin (TI) Using the Gen2C Inhaler

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Regular Human Insulin; Drug: Technosphere Insulin Inhalation Powder 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)

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Regular Human Insulin; Subcutaneous injection	Drug: Regular Human Insulin; Subcutaneous injection
Experimental: TI and Regular Human Insulin; All subjects have 4 clamp procedures with 10, 30, 60,80 units of TI and 1 clamp with 15 IU Regular Human Insulin	Drug: Technosphere Insulin Inhalation Powder using the Gen2C inhaler; Inhalation Powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	crossover 4 times over the course of up to 5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Timepoints: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180 and 240 minutes after administration of TI dosing; 0, 15, 30, 60, 90, 120, 180, 240, 300, 360, 480 and 600 minutes after RHI dosing	crossover 5 times over the course of up to 6 weeks
Area-under-the-serum glucose infusion rate (GIR AUC0-240min) for TI compared to AUC0-600min for RHI	Timepoints for TI: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180 and 240 minutes after TI dosing Timepoints: 0, 15, 30, 60, 90, 120, 180, 240, 300, 360, 480 and 600 minutes after RHI dosing	crossover 5 times over the course of up to 6 weeks
Safety variables included adverse events (AEs), clinical laboratory tests, vital signs and physical examinations		crossover 5 times for up to 6 weeks

Collaborators and Investigators

• Sponsor: Mannkind Corporation
• Investigators: Study Chair: Chief Medical Officer, Mannkind Corporation

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: December 5, 2011
• First Submitted That Met QC Criteria: December 9, 2011
• First Posted (Estimate): December 13, 2011

Study Record Updates

• Last Update Posted (Estimate): September 7, 2012
• Last Update Submitted That Met QC Criteria: September 5, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: PK; PD
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: MKC-TI-176