E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to assess whether a simple initial dose prescription of inhaled insulin (Exubera) achieves glycemic control (HbA1c) after 16 weeks that is noninferior compared to the standard weight-based formula. |
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E.2.2 | Secondary objectives of the trial |
To assess • Speed of achieving a stable prescribed dose • Glucose control at 16 weeks • Incidence of hypoglycemia during the first 4 weeks and over 16 weeks • Safety and tolerability of Exubera |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 1. Signed informed consent. 2. Age ≥ 18 years 3. Diagnosis of type 2 diabetes made ≥ 6 months prior to study entry, as defined by the American Diabetes Association (Diabetes Care 25:S5-S20, 2002). 4. HbA1c ≥ 7.0% at screening 5. Patient should be currently treated and on a stable dose of at least two oral hypoglycemic agents for at least 3 months prior to study entry. |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the trial: 1. Type 1 diabetes 2. Known allergy to insulin 3. Smoking: current or any in the past 6 months; smoking is not permitted at any time during the study 4. Current treatment with insulin 5. Current chronic inhaled or systemic corticosteroid treatment likely to be of metabolic effect (prednisone equivalent >2 mg/day); intercurrent treatment at a higher dose is allowed if treatment duration does not exceed 2 weeks 6. Active Liver disease; ALT ≥ 1.5 times the upper limit of normal (ULN) reference range for the central lab at screening. Evidence within the preceding six months of hepatic dysfunction e.g., AST, ALT, two and a half (2.5) times the upper limit of normal or hepatic disease, e.g., hepatitis,jaundice, cirrhosis or history of developing abnormal liver function tests (LFTs) on thiazolidinediones. Patients with an elevated ALT ≥ 1.5 times ULN due to hepatic steatosis are permitted to enter the study. 7. Pulmonary Conditions: • Less than 70% of predicted FEV1 at Visit 1 • Significant pulmonary diseases including poorlycontrolled asthma, clinically significant obstructive pulmonary disease or other significant respiratory disease. 8. Cardiovascular conditions: • 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. • Poorly-controlled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >110 mmHg) on two readings (sitting). • Abnormal screening ECG: predominant rhythm other than normal sinus A-V block greater than first degree resting heart rate > 100 or < 50 bpm. The principal investigator, or other designated physician at each site, will be responsible for deciding the clinical significance of any abnormal ECG findings. 9. Kidney disease: • History of renal transplantation or current renal dialysis • Clinical nephrotic syndrome, or significant renal dysfunction or disease based on estimated creatinine clearance < 65 mL/min (25), and/or a serum creatinine greater or equal to 1.5 mg/dl (133 mmol/L) in males and greater or equal to 1.4 mg/dl (124mmol/L) in females and /or BUN >50 mg/dl, whichever is worse. 10. Any other clinically significant abnormalities on screening laboratory evaluation (unless discussed with and approved by a Pfizer clinician) 11. History of substance abuse or alcoholism within the past 5 years, and psychiatric disorders that would interfere with the patient’s ability to complete the study 12. Any current malignancy except: • those ≥ 5 years ago without recurrence excised • basalioma or squamous cell cancer 13. Clinically significant major organ system disease such as active infection (e.g., HIV, Hepatitis), or history of severe infection, during the 30 days prior to screening Any concurrent illness other than diabetes mellitus not controlled by a stable therapeutic regimen 14. Patients with circumstances or abnormalities (e.g.,blindness or a history of noncompliance) that would interfere with the interpretation of safety or efficacy data or the completion of the study 15. Pregnant or intent to become pregnant or breastfeeding during study or absence of adequate contraceptive measures. The recommended contraceptive measures include (a) oral contraceptives, (b) intrauterine device (IUD), (c) implanted contraceptive (such as Norplant®), (d) injectable contraceptive (such as Depo-Provera®), or (e) a barrier method of contraception, e.g., condom and/or diaphragm with spermicide or (f) sexual partner uses a condom or is surgically sterilized, or (g) sexually inactive 16. Failure to adhere to protocol requirements during the screening period 17. Inpatient surgery anticipated during the study period 18. Investigator or immediate family i.e., current spouse, parent, naturally or adopted child, stepchild living in the investigator’s household, grandparent, grandchild 19. Donation of blood or blood products for transfusion during the 30 days prior to initiation of treatment with study drug (if applicable), at any time during the study or 30 days after completion of the study 20. Participation in any other studies involving investigational products within the two (2) months prior to entry in the study or any time during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Primary: Change in HbA1c from baseline after 16 weeks of treatment. Secondary: • Time from initial to stable prescribed dose for Exubera*. • Change from baseline in fasting plasma glucose at week 1, 2, 4, 8, 12 and 16. • Change from baseline in mean average blood glucose based on 7-point blood glucose profile collected at week 1, 4, 8 and at 16 • Proportion of subjects achieving HbA1c < 7.0% or < 6.5% at week 16 • Incidence of overall and severe hypoglycemia collected at baseline (week 0) and at week 1, 2, 4, 8, 12 and 16 • Incidence of nocturnal hypoglycemia collected at baseline (week 0) and at week 1, 2, 4, 8, 12 and 16 • Safety and tolerability of Exubera
*Stable prescribed dose will be defined in two ways, each applied to the whole study population, as follows: 1. Exubera Total Daily Dose prescribed by a study health care professional that has remained unchanged for at least 3 consecutive assessments. 2. Exubera Total Daily Dose prescribed by a study health care professional that has remained unchanged for at least 4 weeks. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
same drug but different dose |
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E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |