| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10045242 | | E.1.2 | Term | Type II diabetes mellitus | |
| 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 | · To investigate and compare the effect of 500µg roflumilast once daily versus placebo once daily over 12 weeks on HbA1c in patients with diabetes mellitus type 2.
·To investigate and compare the safety and tolerability of roflumilast in patients with diabetes mellitus type 2
| |
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | · Given written informed consent
· Age > 35 and < or = 70 years
· Patients with diagnosis of type 2 diabetes according to ADA criteria (American Diabetic Association) and inadequately controlled on diet and exercise alone.
· HbA1c at baseline: > or = 7.5 – 8.5 %
· BMI between > or = 26 and < or =35 kg/m2
· Willingness of patient to check his/her blood glucose with equipment provided by the sponsor during the treatment phase in case of hypo- / hyperglycemia episodes
· Willingness to adhere to the physician’s advise to comply with diet and exercise
| |
| E.4 | Principal exclusion criteria | · Patients diagnosed with type-1 diabetes or diabetes secondary to pancreatitis or resection of pancreas
· Patients diagnosed with a heamoglobinopathies, haemolytic anaemia or other diseases which interfere with HbA1c measurement
· Non-euthyroid patients or patients with a non-controlled hypo- or hyperthyroidysm
· Reported gain or loss of more than 5% of body weight within the last 2 month prior to V0
· Treatment with any diabetes medication prior to V0
· Treatment with any weight-loss medication within 3 months prior to V0
· Treatment with any not allowed medication or nutrition additives
· Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation (as assessed by the investigator)
· Known infection with HIV, active hepatitis and/or active liver disease or unexplained elevations in ALT or AST (greater than 3X above the upper limit of normal for ALT or AST confirmed with repeat testing)
· History of clinically relevant diseases of the liver, kidney (including serum creatinine greater than 2.0 mg/dL) or gastrointestinal systems
· Diagnosis or history of cancer (other than basal cell carcinoma) within 5 years prior to study start
· Clinically significant cardial abnormalities (diagnosed clinically or by x-ray / ECG) that are not related to type 2 diabetes mellitus and that require further evaluation
· Diagnosis or history of stroke, myocardial infarct, chronic stable and unstable angina pectoris, ventricular arrhythmia, symptomatic congestive heart failure [NYHA III or IV) within 5 years prior to study start
· Uncontrolled hypertension, defined as blood pressure > 160/90 mmHg
· Presence or history of psychosis or psychotic disorders
· Suspected hypersensitivity to the study medication
· Pregnancy, breast feeding, oocyte donation or oocyte implantation planned during the trial
· Female patients of childbearing potential (< 2 years postmenopausal or not sugically sterile), not using and not willing to continue using one of the following highly effective means of birth control with failure rates of less than 1% per year for > 30 days prior to enrollment, for the duration of the study, and for at least 30 days following the last dose of study medication:
- Combined oral contraceptives
- Approved implantable or injectable contraceptives
- Intrauterine contraceptives
In case none of the above mentioned contraceptive methods complying with the note for guidance CPMP/ICH/286/95 (modification) can be tolerated, the decision on an appropriate contraceptive method should be taken based on the expert advise of an obstetrician/gynecologist.
· Participation in another study (use of investigational product) within 30 days preceding the baseline visit V0 or re-entry of patients already enrolled in this trial.
· Participation in a clinical study with study medication for weight loss or type 2 diabetes
· Suspected inability or unwillingness to comply with study procedures
· History or presence of alcohol or drug dependence within 7 years prior to Screening
· Inability to follow study procedures due to e.g. language problems
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| E.5 End points |
| E.5.1 | Primary end point(s) | Efficacy:
Primary variable:
· mean changes in HbA1c from baseline to endpoint/last value.
Secondary variables:
· mean changes in HbA1c from baseline to all scheduled post-randomization timepoints.
· mean changes in FFA, glycerol, glucose, glucagons, insulin, C-peptide after a fixed meal measured over a time course to be followed over 5 hrs, with measurements each 30 min.
· mean changes in body weight, waist and hip measurements data, BMI
· onset of action (FPG as relevant parameter)
· mean changes in serum lipids (HDL, LDL,TGs), fructosamine, glycerol, free fatty acids and plasma insulin, CRP, IL-6, TNF-a, ICAM-1, E-selectin, PAI-1, adiponectin, leptine,
Safety:
· Incidence of hypo- and hyperglycemic episodes.
· Adverse events,
· Changes in laboratory values,
· Changes in physical examination findings including electrocardiograms (ECG [PR, QRS, QT intervals],
· Changes in vital signs blood pressure (BP) and heart rate (HR)
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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 | No |
| E.6.10 | Pharmacogenetic | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| 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 | |
| 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 | |
| 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 | 17 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 17 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
