Bioequivalence
Conditions
Brief summary
The present clinical trial will be conducted to compare the bioavailability of rivastigmine and assess bioequivalence at steady-state of the Test product RIV-TDS 13.3 mg/24 h and the marketed Reference product Exelon® 13.3 mg/24 hours transdermal patch after multiple patch application. Each of both treatments will last 5 days.
Detailed description
This will be a single centre, open-label, randomised (order of treatments), balanced, 2-period, 2-sequence, cross-over trial with multiple applications of rivastigmine transdermal patches. There will be no wash-out, i.e. the first investigational patch application of the second study period will take place the day of the last investigational patch removal of the first study period (direct switch-over). Prior to start of first treatment, there will be an adaptation phase with 4 consecutive applications of Exelon® 9.5 mg/24 hours transdermal patch over a period of 4 days (each patch will be applied for 24 hours). Following the removal of the last investigational patch in period II, there will be a post-treatment tapering phase with 2 consecutive applications of Exelon® 9.5 mg/24 hours transdermal patch over a period of 2 days (each patch will be applied for 24 hours). Furthermore, during the adaptation phase, both study periods and the tapering phase, scopolamine transdermal patches will be applied as co-medication to attenuate effects of rivastigmine and reduce Adverse Events.
Interventions
DRUGRIV-TDS 13.3 mg/24 h
5 consecutive transdermal patch applications, each with a nominal release rate of 13.3 mg/24 hours
DRUGExelon® 13.3 mg/24 hours transdermal patch
5 consecutive transdermal patch applications, each with a nominal release rate of 13.3 mg/24 hours
Sponsors
SocraMetrics GmbH
SocraTec R&D GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Sex: male 2. Ethnic origin: Caucasian 3. Age: 18 - 50 years, inclusive 4. Body-mass index2 (BMI): \>=18.5 kg/m² and \<= 30.0 kg/m² 5. Good state of health 6. Non-smoker or ex-smoker for at least 6 months 7. Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial
Exclusion criteria
1. Existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredients (especially sick sinus syndrome or conduction defects such as sino-atrial block, atrio-ventricular block, arrhythmia, bradycardia) 2. Existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredients (especially predisposition to urinary obstruction and seizures or other conditions with difficulty in passing water owing to an impeded flow of urine (e.g. in diseases of the prostate)) 3. Existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredients (especially active gastric or duodenal ulcers or predisposition to these conditions, pyloric stenosis, intestinal obstruction) 4. History of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders (e.g. cerebral sclerosis) 5. History of asthma or obstructive pulmonary disease 6. Glaucoma or any indications from case history that there might be raised intra-ocular pressure (e.g. pressure pain, blurred vision, glaucomatous halo) 7. Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations or previous history of application site reactions suggestive of allergic contact dermatitis with rivastigmine or scopolamine patch 8. Subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator 9. Body weight below 65 kg 10. Systolic blood pressure \< 90 or ≥ 140 mmHg 11. Diastolic blood pressure \< 60 or \>90 mmHg 12. Heart rate \< 60 bpm or \> 90 bpm 13. QTc interval \> 450 ms 14. Laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator 15. ASAT \> 20 % ULN, ALAT \> 10 % ULN, bilirubin \> 20% ULN (except in case of existing Morbus Gilbert-Meulengracht deduced from anamnesis/medical history) and creatinine \> 0.1 mg/dL ULN (limit of \> 0.1 mg/dL correspondents to of \> 9 μmol/l ULN). 16. Positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test or anti-HCV-test 17. Presence or history of acute or chronic diseases especially of the skin, which could affect dermal absorption or metabolism, which may interfere with the bioavailability and /or the pharmacokinetics of scopolamine or rivastigmine patches based on assessment of the investigator 18. Skin abnormality (e.g. tattoo or scar) at the application site 19. Acute or chronic diseases which may interfere with the pharmacokinetics of scopolamine or rivastigmine patches 20. History of or current drug or alcohol dependence 21. Positive alcohol or drug test at screening examination 22. Regular intake of alcoholic food or beverages of ≥ 40 g pure ethanol per day 23. Subjects who are on a diet which could affect the pharmacokinetics of the active ingredients 24. Regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day 25. Blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the subject 26. Administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject 27. Regular treatment with any systemically available medication 28. Subjects practising top-performance sports (more than 4 x 2 h per week) 29. Subjects suspected or known not to follow instructions 30. Subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-tau,ss | from 0 to 24 hours following the 5th patch application | Area under the plasma concentration vs. time curve at steady state for rivastigmine |
| Ctau,ss | from 0 to 24 hours following the 5th patch application | (Trough) minimum plasma concentration at the end of the dosing interval at steady state for rivastigmine |
| Cmax,ss | from 0 to 24 hours following the 5th patch application | Maximum plasma concentration within the dosing interval at steady state for rivastigmine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patch adhesion | from first investigational patch application until removal of the last investigational patch (approx. 10 days) | one-sided lower 90% confidence limit of mean adherence percentage at the end of the dosing interval of the 5th patch |
| Skin irritation | from first investigational patch removal until last investigational patch removal (approx. 10 days) | frequency of scores for quantification of skin irritation per treatment and time point |
| Adverse events | approximately 2 weeks, through study completion in case of follow-up | descriptive evaluation of frequency and intensity, relationship to the IMP, action taken, outcome, seriousness, period and treatment |
Countries
Germany
Outcome results
None listed