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 | 8.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012601 |
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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 is to compare the efficacy between subjects who are treated with the combination of OHA’s and Exubera® compared to subjects treated with usual diabetes care, by looking at the mean reduction in HbA1c after 24 weeks in both groups. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to further explore the efficacy, safety and humanistic impact by evaluating the following secondary endpoints: •Proportion of subjects achieving good glycemic control (HbA1c ≤6.5% and ≤7.0%). •Time to achieve glycemic control (HbA1c ≤6.5% and HbA1c ≤7.0%). •Change from baseline to end of treatment in fasting plasma glucose (FPG) level. •Time course of change in fasting plasma glucose levels. •Incidence and severity of hypoglycemia. •Change from baseline to end of treatment in body weight and body mass index. •Change from baseline to end of treatment in fasting lipid profile. •Number of subjects who require additional treatment 12 weeks after randomization. •Number of subjects who discontinue due to insufficient clinical response. •Change from baseline to end of treatment in pulmonary forced expiratory volume in one second (FEV1). •Incidence and severity of clinical adverse events. •Subject reported treatment satisfaction and health status. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Subject has given written informed consent to participate in the study. 2. Age ≥35 years and ≤80 years with a diagnosis of type 2 diabetes mellitus, as defined by the American Diabetes Association (Diabetes Care 25: S5-S20, 2002)made at least 6 months prior to screening. 3. Has a screening HbA1c ≥8% and ≤11.0%. 4. Has a Body Mass Index (BMI) ≥23 kg/m 2 and ≤40 kg/m 2 , calculated using the following formula BMI = Weight in Kilograms (Height in Meters) x (Height in Meters)
or
BMI = ( Weight in Kilograms ) x 10,000 (Height in centimeters) x (Height in centimeters)
5. Is currently treated and on a stable dose of two OHA’s for at least 3 months prior to study entry. 6. Has documentation of a full ophthalmologic exam (including fundoscopy) by an ophthalmologist within 6 months prior to randomization. 7. Is willing and able to perform specified home blood glucose monitoring (HBGM) and to otherwise comply with study protocol requirements. 8. Has the ability to understand the requirements of the study. |
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E.4 | Principal exclusion criteria |
1. Has Type 1 Diabetes mellitus as defined by American Diabetes Association (ADA) criteria. 2. Has Type 2 diabetes chronically treated with insulin regimen (only, or in combination with OHA’s). 3. Has Type 2 diabetes and is not treated with OHA or treated with only one OHA, or those treated with OHA’s that are prohibited for use in combination with other OHA’s or with insulin as per country specific labeling requirements for such agents. 4. Is currently treated with TZD’s. Subject will be allowed to enter the study after a 12-week wash out period. 5. Has a known allergy to insulin. 6. Has a "brittle" diabetes or a predisposition to severe hypoglycemia 7. Has any of the following metabolic conditions: •Significant hypoglycemia risk e.g., history of >2 severe (as defined by DCCT) hypoglycemic episodes within past 6 months •Known adrenal insufficiency •Symptomatic autonomic neuropathy and/or •Current chronic 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. Corticosteroids given topically and as intra-articular injections are allowed during the course of the trial 8. Has an impaired hepatic function, as shown by, but not limited to, ALT (SGPT) or AST (SGOT) above 2x the upper limit of normal as measured at visit 1. 9. Has an impaired renal function, as shown by, but not limited to, serum creatinine >177 µmol/l (>2 mg/dl) as measured at visit 1 or current renal dialysis. 10. Has any other clinically significant abnormalities on screening laboratory evaluation 11. Has hemoglobinopathy or chronic anemia or any other condition known to interfere with HbA1c determination. 12. Has active proliferative diabetic retinopathy 13. Has donated blood or had a transfusion of blood/blood products during the trial and 2 months prior to screening. 14. If the subject is female who is pregnant, lactating or planning to become pregnant during the study. 15. Has any of the following pulmonary conditions: •Frankly abnormal FEV1 at Week –1, defined as FEV1 <70% of predicted. •Clinically significant abnormalities on screening chest X-ray (or chest MRI). 16. Is unable to perform assessment of FEV1 according to predefined quality criteria following American Thoracic Society (ATS) or local country specific guidelines. 17. Has smoked within the last 6 months prior to entry in the study. Smoking is not permitted at any time during this study. 18. Has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study. 19. Has any clinically significant major organ system disease such as relevant cardiovascular, gastrointestinal, hepatic, neurological, endocrine, haematological or other major systemic diseases which, in the investigator’s opinion, make implementation of the protocol or interpretation of the study results difficult. Well controlled, stable disorders such as essential hypertension and complications directly related to diabetes (such as peripheral neuropathy, mild nephropathy or stable retinopathy) would not exclude a subject. 20. Has an active infection (e.g., HIV, hepatitis), or a history of severe infection, during the 30 days prior to screening. 21. Is being treated or likely to require treatment during the study period with drugs not permitted by the clinical study protocol. 22. Has participatied in any other studies involving investigational or marketed products within the two (2) months prior to entry in the study. 23. Has participated in any prior Exubera® or other inhaled insulin clinical trials. 24. Has a history of drug or alcohol abuse within the last 2 years or current addiction to substances of abuse. 25. Has any current malignancy except: a. Those ≥5 years ago without recurrence. b. Excised basal cell carcinoma or squamous cell cancer. 26. Is a night shift workers. 27. Is unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, or is unlikely to complete the study. 28. Is an investigator, sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Diabetes–related Endpoints : The primary efficacy endpoint will be change from baseline in HbA1c at the end of the treatment period. Secondary endpoints include the percentage of subjects who have an HbA1c of ≤7% and ≤6.5% at the end of the treatment period, rates of hypoglycemia, changes in body weight at week 24 compared to baseline, time to achieve good control - an HbA1c of ≤7% and ≤6.5%.
Safety Endpoints: Clinical laboratory tests, pulmonary and liver function tests, vital signs and clinical adverse events including hypoglycemia will be evaluated. |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 20 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 20 |