Type 1 Diabetes MedDRA version: 8.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus
Conditions
Interventions
Trade Name: Exubera
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Human Insulin
CAS Number: 11061-68-0
Current Sponsor code: CP 464 005
Concentration unit: mg milligram(s)
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 1. Diagnosis: Subjects with type 1 diabetes mellitus, as defined by the American Diabetes Association (Diabetes Care 2005 28: S37-42), for more than one year. 2. Subjects who have not participated in a prior inhaled insulin clinical trial. 3. Age: = 18 years. 4. Current Therapy: For the 2 months prior to screening, subjects must have been on a stable insulin regimen involving at least 3 injections daily of insulin or an insulin analogue (i.e., no change in the type(s) of insulin or in the schedule of injections; dose changes are acceptable). 5. Screening (week-4) HbA1c between 5.5% and 9.0% inclusive. 6. Fasting plasma C-peptide = 0.20 nmol/L. 7. Body Mass Index = 30. (BMI = Weight[kg] ÷ {Height[m]}2 8. Subjects must have documentation of an ophthalmologic exam within 1 year of screening demonstrating no active proliferative retinopathy requiring treatment during the study. Documentation must be obtained prior to randomization. 9. Subjects must be able to demonstrate the ability to adequately perform spirometry tests. 10. Subjects willing to perform specified home blood glucose monitoring and otherwise to comply with study protocol requirements. 11. The investigator will be responsible for obtaining written informed consent prior to the subject participating in the study. 12. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the trial: 1. Pregnant or lactating females, or females planning to become pregnant during the study. Females of childbearing potential must have a negative pregnancy test at screening and be using a medically accepted contraception method such as systemic hormones (birth control pills, hormonal implant device), intra-uterine device, barrier method (diaphragm with intravaginal spermicide, cervical cap, male or female condom). Females who become pregnant or who are unable or unwilling to maintain adequate contraception for the duration of the study will be withdrawn from the study. 2. Donation of blood or receipt of blood transfusion during the 12 weeks prior to the screening visit, for the duration of the study, or for 30 days after completion of the study. 3. Use of any other investigational drug during the two months prior to screening and for the duration of the study. 4. Subjects on insulin pump treatment as part of their MDI regime during the 2 months prior to screening. 5. Subjects with “brittle” diabetes or a predisposition to severe hypoglycemia — i.e., 2 or more severe hypoglycemic episodes within the past 6 months, or any hospitalization or emergency room visit due to poor diabetic control within the past 6 months. Similarly, during the baseline run-in period, any subject with more than one severe hypoglycemic episode or any hospitalization or emergency room visit due to poor diabetic control will be excluded from randomization. Severe hypoglycemia is defined in section 8.13.2 (SAFETY REPORTING, Other Safety Parameters, Hypoglycemia). 6. Pulmonary Conditions: • FEV1, defined as FEV1 2 mg/day); intercurrent treatment at a higher dose is allowed if treatment duration does not exceed 2 weeks. c. Patients with celiac disease 9. Active Liver disease; ALT = 2.0 times the upper limit of normal reference range for the central lab at screening. Evidence within the preceding six months of hepatic dysfunction e.g., AST or ALT 2.0 times or more of the upper limit of normal or hepatic disease, e.g., hepatitis, jaundice, cirrhosis. 10. Cardiovascular conditions: a. Significant cardiovascular dysfunction and/or history including hospitalization within the preceding six months, e.g., congestive heart failure or serious arrhythmia, myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks or cerebrovascular accident. b. Poorly-controlled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >110 mmHg) on two readings (sitting). c. Abnormal screening ECG: • predominant rhythm other than normal sinus; • A-V block greater than first degree; • resting heart rate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate non-inferiority of an insulin regimen using insulin glargine as the basal insulin with Exubera as the mealtime insulin, compared to a regimen using insulin glargine as the basal insulin and insulin lispro as the mealtime insulin in terms of glycemic control (HbA1c) after 52 weeks of treatment with each treatment regimen.;Secondary Objective: Secondary objectives of the study include durability of glycemic control additional measurements of glycemic control (fasting plasma glucose - FPG, postprandial glucose - PPG), hypoglycemia, body weight and body mass index changes, patient reported outcomes as well as the safety of both treatment regimens, each after 52 weeks of treatment with each treatment regimen.;Primary end point(s): 1- The primary efficacy endpoint is the change in % HbA1c from baseline (average of week –1 and week 0 HbA1c values) to week 52. Change from baseline in HbA1c between the two arms will be compared following adjustment according to baseline HbA1c values. 2- Secondary endpoints (reported at all post-baseline visits up to and including Week 52 where relevant data was captured; see Schedule of Activities for further detail) include: • Hypoglycemic event rates during the entire study (see protocol section 6.3.2.3 for definitions of hypoglycemia): • Non-severe hypoglycemic event rates. • Total and severe hypoglycemic event rates in subjects who attain HbA1c levels less than 6.5%, less than 7%, less than 8% and those who fail with HbA1c levels greater than or equal to 8% at the end of the study. • Percentage of subjects with an HbA1c < 8 %,< 7%, <6.5%, and = 8% at 24 weeks and at the end of study/early termination. • Percentage of subjects with =0.5, =0.7 and =1.0% absolute reduction in HbA1c levels at the end of the study from baseline levels • Percentage of subjects who attain target FPG values 4.0-6.5 mmol/l (72-117 mg/dl) at each evaluation • Change in fasting plasma glucose f | — |
Countries
Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Netherlands, Portugal, Sweden, United Kingdom
Outcome results
None listed