Bioavailability of Technosphere® Insulin Versus Subcutaneous Regular Human Insulin in Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by:
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT00511719
First received: August 3, 2007
Last updated: June 28, 2011
Last verified: June 2011
  Purpose

The purpose of this study is to compare the kinetics and biodynamics of inhaled Technosphere Insulin with those of subcutaneous (SC) regular human insulin.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Technosphere Insulin
Drug: Actrapid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Controlled, Single-Center, Open-Label,Randomized, Replicated, Crossover Isoglycemic Glucose Clamp Study Evaluating Intrapatient Variability in Bioavailability of Technosphere® Insulin Compared With Subcutaneous Regular Human Insulin in Patients With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Mannkind Corporation:

Primary Outcome Measures:
  • Dose-corrected area-under-the serum insulin concentration vs. time curve (AUC0-540 min) for inhaled Technosphere® Insulin compared to that of subcutaneous regular human insulin [ Time Frame: crossover approx every 2 weeks for up to 10 weeks ] [ Designated as safety issue: No ]
  • Area under the glucose infusion rate (GIR AUC0-540 min) for Technosphere® Insulin compared to regular human insulin [ Time Frame: crossover approx every 2 weeks for up to 10 weeks ] [ Designated as safety issue: No ]
  • Intra-patient and inter-patient comparison of CV % between treatments was based on a t-test.for bioavailability (ie, SI AUC0-540 min) & bioeffect (ie, GIR AUC0-540 min) [ Time Frame: crossover approx every 2 weeks for up to 10 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety variables included adverse events, HbA1c, pulmonary function tests, and diabetes-specific signs (ie, hypoglycemia and hyperglycemia) [ Time Frame: crossover approx every 2 weeks for up to 10 weeks ] [ Designated as safety issue: No ]
  • Safety variables included adverse events (AEs), clinical laboratory tests, HbA1c, pulmonary function tests, electrocardiograms, vital signs, physical examinations, and diabetes-specific signs [ Time Frame: crossover approx every 2 weeks for up to 10 weeks ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: February 2004
Study Completion Date: March 2005
Primary Completion Date: April 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Technosphere Insulin
Technosphere Insulin Inhalation Powder
Drug: Technosphere Insulin
48U
Active Comparator: Actrapid
Subcutaneous regular human insulin
Drug: Actrapid
24IU

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical Diagnosis of type 2 diabetes mellitus
  • Current regimen of intensified insulin therapy (defined as separate injections of basal and prandial insulin with at least three injections per day) for at least six months prior to the study, including the use of long-lasting insulin analogue glargine (Lantus)
  • Patients must have been willing to withhold insulin glargine for 24 hours prior to study drug dosing
  • 18 to 65 years old
  • Body Mass Index <35kg/m2
  • HbA1c<9%
  • Non-smoker for at least 2 years
  • If medications (other than oral anti-diabetic agents) in addition to insulin were taken at screening, the patient had to be on a stable regimen as defined by continued use of the same dose of each medication for a period of at least 3 months immediately prior to study enrollment
  • FVC, FEV1, and VC all >80% of expected normal
  • Written informed consent

Exclusion Criteria:

  • Diabetes mellitus type 1
  • Current treatment (within the last 30 days) with oral anti-diabetic agents
  • Regular pre-prandial doses of regular subcutaneous insulin for more than 30 IU per meal
  • Intake of any drug or herbal preparation that, in the evaluation of the investigator, may interfere with the interpretation of clinical trials results or that is known to cause clinically relevant interference with insulin action, glucose utilization or recovery from hypoglycemia (eg, systematic steroid)
  • HIstory of hypersensitivity to the drug or to drugs with similar chemical structures
  • Treatment with any investigation drug within 3 months prior to enrollment or during this study
  • Progressive fatal disease
  • History of malignancy within 5 years of study entry (other than basal cell carcinoma)
  • History of drug or alcohol abuse
  • Evidence of severe secondary complications of diabetes (neuropathy, nephropathy as evidenced by creatinine >1.5 mg/dL for females or >1.8 mg/dL for males, grade III or IV retinopathy, or severe peripheral vascular disease)
  • Evidence of gastroparesis, orthostatic hypotension or hypoglycemia unawareness (autonomic neuropathy)
  • Myocardial infraction or stroke within the preceding six months
  • Positive hepatitis B (hepatitis B surface antigen) and /or hepatitis C (hepatitis C antibody) serology and /or positive HIV serology
  • History of presence of clinically significant cardiovascular, hepatic (as evidenced by ALT or AST >3 times the normal reference range), gastrointestinal, neurological, or infectious disorders capable of altering the absorption, metabolism or elimination of drugs, or constituting a significant risk factor when taking the study medications
  • Anemia (hemoglobin concentrations <11 g/dL for females of <g/dL for males)
  • Ongoing respiratory tract infection
  • Pregnancy, lactation, or intention to become pregnant
  • Women of child-bearing potential practicing inadequate birth control (adequate birth control was defined as using oral contraceptives, condoms, or diaphragms with spermicide, intrauterine devices, or surgical sterilization)
  • Regular alcohol intake greater than 14 units*/week, or patients unwilling to stop alcohol during the duration of the study (*1 unit=8 g ethanol, 1/4 liter of beer or 1 glass of wine or 1 measure of spirits)
  • Investigator or site personnel directly affiliated with this study and their immediate families. Immediate family was defined as a spouse, parent, child or sibling, whether biological or legally adopted
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Chief Scientific Officer, Mannkind Coorporation
ClinicalTrials.gov Identifier: NCT00511719     History of Changes
Other Study ID Numbers: MKC-TI-003b2
Study First Received: August 3, 2007
Last Updated: June 28, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014