| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 provide Proof-of-Concept for PSN357AB |
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| E.2.2 | Secondary objectives of the trial |
To investigate the pharmacodynamics of PSN357AB in patients with type-2 diabetes in relation to doses.
To assess the safety and tolerability.
To investigate the dose linearity (dose proportionality), accumulation and PK of the ascending doses |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Patients must give their signed informed consent before any trial related activities. Trial related activities are any procedures that would not have been performed during the normal management of the patient.
2. Patients diagnosed with type-2 diabetes according to WHO criteria.
3. Diabetes treatment: Diet treatment only for at least 2 weeks prior to screening, or ongoing treatment with oral antidiabetics, which must be withdrawn for a minimum of 2 weeks before dosing.
4. Males aged 30 <= age <= 74 years, or females aged 30 <= age <= 74 years if hysterectomised and therefore of no childbearing potential, or females aged 55 <= age <= 74 years of no child-bearing potential as defined by amenorrhoea at least for the 12 months prior to inclusion.
5. Body mass index (BMI) between 22 and 35 kg/m2, inclusive.
6. 7.5 <= HbA1C <= 10.0% at screening.
7. Laboratory values within the normal range, except ALT and AST, which might be 1.5 fold above the upper limit of normal.
8. Plasma C-peptide within the normal reference range.
9. Fasting blood glucose (FBG) measured in plasma at screening:
– 7.2 mmol/L <= FBG <= 15.0 mmol/L in patients on diet
– 7.2 mmol/L <= FBG <= 12.0 mmol/L in patients with oral antidiabetics
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|
| E.4 | Principal exclusion criteria |
1. Patients on insulin treatment.
2. Pharmacological treatment with any of the following: systemic steroids (within the last month), beta-blockers, and hormones (within the last month, hormone replacement therapy by female patients excluded).
3. Any medication that the Investigator expects could interfere with blood glucose levels.
4. Diabetic side complications
5. History of severe pancreatitis interfering with blood glucose levels (as evaluated by the Investigator).
6. History of, or current impaired hepatic function, ALT or alkaline phosphatase >= 2 times upper normal level, and clinically increased liver size.
7. Creatinine clearance (calculated according to the Cockcroft-Gault formula) that in the opinion of the investigaor does indicate renal impairment:
– Creatinine clearance (mL×min-1) = (140 – age) × body weight (kg) (× 0.85 for females)/72 × serum creatinine (mg/dL)
8. Hypertension (whether treated or not): systolic blood pressure > 160 mmHg blood pressure and/or >= 99 mmHg for diastolic blood pressure in the supine position.
9. History of, or current cardiac problems, as angina pectoris, myocardial infarction, or symptoms of ischemic heart disease.
10. Supine heart rate higher than 90 beats/min at each of 2 consecutive evaluations.
11. Clinically significant abnormal 12-lead ECG (as evaluated by the Investigator).
12. Positive serum pregnancy test (for female patients only).
13. Any disease or condition which the Investigator feels will interfere with the trial.
14. Patients who are known to have serum hepatitis or who are carriers of the Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies, or have a positive result to the test for HIV antibodies.
15. Patients with acute gastrointestinal symptoms at the time of entering the trial (e.g. nausea, vomiting, diarrhoea, or heartburn).
16. Any clinically significant abnormal laboratory test results at screening.
17. Patients who have received an investigational drug (new chemical entity or licensed product) in the month preceding the start of dosing.
18. Patients who have a significant history of alcoholism or drug/chemical abuse, or who have a positive result in the urine drug/alcohol screen, or who consume more than 21 units of alcohol per week (one unit of alcohol equals about 250 mL of beer or lager, one glass of wine, or 20 mL spirits).
19. Patients, who have passed a blood donation within the three months of Day –1 or plasma within two weeks of Day –1.
20. Patients with a significant use of caffeine containing beverages (greater than eight cups per day).
21. Patients who smoke more than 10 cigarettes, or the equivalent, per day and are unable to refrain from smoking during 4 days prior to the first dosing day and during the confinement period.
22. Patients with mental incapacity or language barriers which preclude adequate understanding or co-operation, who are unwilling to participate in the study, or who in the opinion of their general practitioner or the Investigator should not participate in the study.
23. Patients who have taken part in strenuous exercise within four days prior to dosing in this trial. Whether strenuous exercise has been undertaken will be evaluated by the Investigator, and strenuous exercise is not allowed during the trial.
24. Fasting blood glucose > 15 mmol/L more than three times during a 48-hour period from screening to the end of the run-in phase as measured in plasma.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Pharmacodynamic endpoints include: Insulin, glucose (including OGTT results), food intake (% meal consumption) and satiety.
In case of significant changes in weight/fasting blood glucose levels from screening to and within the run-in phase (i.e., measurements at Day –4 and Day –1), but parameters still being within the limits given in the inclusion/exclusion criteria, these should be included in the overall evaluation of the pharmacodynamic endpoints. |
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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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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) | 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| time-lagged, dose escalation |
|
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
|
The approximate study duration for each subject will be at least 35 days to a maximum of 63 days. It is expected that the study will last from November 2005 until April 2006.
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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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
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