Bioavailability of Technosphere® Insulin Versus Subcutaneous Regular Human Insulin in Type 2 Diabetes
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Technosphere Insulin
Actrapid
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Technosphere Insulin
Actrapid
Arm Description
Technosphere Insulin Inhalation Powder
Subcutaneous regular human insulin
Outcomes
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
Area under the glucose infusion rate (GIR AUC0-540 min) for Technosphere® Insulin compared to regular human insulin
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)
Secondary Outcome Measures
Safety variables included adverse events, HbA1c, pulmonary function tests, and diabetes-specific signs (ie, hypoglycemia and hyperglycemia)
Safety variables included adverse events (AEs), clinical laboratory tests, HbA1c, pulmonary function tests, electrocardiograms, vital signs, physical examinations, and diabetes-specific signs
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00511719
Brief Title
Bioavailability of Technosphere® Insulin Versus Subcutaneous Regular Human Insulin in Type 2 Diabetes
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
April 2004 (Actual)
Study Completion Date
March 2005 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Mannkind Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to compare the kinetics and biodynamics of inhaled Technosphere Insulin with those of subcutaneous (SC) regular human insulin.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Technosphere Insulin
Arm Type
Experimental
Arm Description
Technosphere Insulin Inhalation Powder
Arm Title
Actrapid
Arm Type
Active Comparator
Arm Description
Subcutaneous regular human insulin
Intervention Type
Drug
Intervention Name(s)
Technosphere Insulin
Intervention Description
48U
Intervention Type
Drug
Intervention Name(s)
Actrapid
Intervention Description
24IU
Primary Outcome Measure Information:
Title
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
Title
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
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
12. IPD Sharing Statement
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Bioavailability of Technosphere® Insulin Versus Subcutaneous Regular Human Insulin in Type 2 Diabetes
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