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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT01490762
First received: December 5, 2011
Last updated: September 5, 2012
Last verified: September 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Healthy
 Drug: Technosphere Insulin Inhalation Powder using the Gen2C inhaler
Drug: Regular Human Insulin
 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, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Mannkind Corporation:

Primary Outcome Measures:
  • 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 [ Time Frame: crossover 4 times over the course of up to 5 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) [ Time Frame: crossover 5 times over the course of up to 6 weeks ] [ Designated as safety issue: No ]
    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

  • Area-under-the-serum glucose infusion rate (GIR AUC0-240min) for TI compared to AUC0-600min for RHI [ Time Frame: crossover 5 times over the course of up to 6 weeks ] [ Designated as safety issue: No ]
    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

  • Safety variables included adverse events (AEs), clinical laboratory tests, vital signs and physical examinations [ Time Frame: crossover 5 times for up to 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: December 2011
Study Completion Date: July 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01490762

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: NCT01490762     History of Changes
Other Study ID Numbers: MKC-TI-176
Study First Received: December 5, 2011
Last Updated: September 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mannkind Corporation:
PK
PD

Additional relevant MeSH terms:
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013