Rivastigmine Bioequivalence Trial With Multiple Application of Transdermal Patches (9.5mg/24h)

Bioequivalence Clinical Trial

Official title:

Open, Randomized, 2-period, 2-sequence, Cross-over Relative Bioavailability Study to Investigate the Pharmacokinetics and to Assess the Bioequivalence of a Rivastigmine Test Patch Formulation 9.5 mg/24 h (Twice Weekly Patch) Compared to the Reference Exelon® 9.5 mg/24 h (Once Daily Patch) Applied for 11 Days

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03659435
• Other study ID #: 1352riv18ct
• Secondary ID: 2018-001570-18C_
• Status: Completed
• Phase: Phase 1
• Start date: August 22, 2018
• Est. completion date: November 28, 2018

Study information

• Verified date: September 2019
• Source: SocraTec R&D GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The present clinical trial will be conducted in order to compare the bioavailability of rivastigmine and to assess bioequivalence at steady-state of the Test product RID-TDS 9.5 mg/24 h (Luye Pharma AG, Germany) and the marketed Reference product Exelon® 9.5 mg/24 h transdermales Pflaster (Novartis Pharma GmbH, Germany) after multiple patch application. Each of both treatments will last for 11 days with a washout period of 14 days between the treatments.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: November 28, 2018
• Est. primary completion date: November 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. sex: male

2. age: 18-55 years, inclusive

3. body-mass index2 (BMI): =18.5 kg/m² and = 30.0 kg/m²

4. good state of health as determined by no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination (including vital sign) and/or ECG, as determined by the investigator

5. non-smoker or ex-smoker for at least 1 month

6. 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 ingredient (especially sick sinus syndrome or conduction defects such as sino-atrial block, atrio-ventricular block)

2. existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient (especially predisposition to urinary obstruction and seizures)

3. existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient (especially active gastric or duodenal ulcers or predisposition to these conditions)

4. history of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders

5. Subjects with chronic obstructive or other pulmonary diseases or bronchial asthma

6. 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 patch

7. subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator

8. systolic blood pressure < 90 or >139 mmHg

9. diastolic blood pressure < 60 or >89 mmHg

10. heart rate < 50 bpm or > 90 bpm

11. body weight below 50 kg

12. QTc interval > 450 ms

13. laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator

14. 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).

15. positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test or anti-HCV-test

16. 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 the IMP based on assessment of the investigator

17. Skin abnormality (e.g. tattoo or scar) at the application site

18. acute or chronic diseases which may interfere with the pharmacokinetics of the IMP

19. history of or current drug or alcohol dependence

20. positive alcohol or drug test at screening examination

21. regular intake of alcoholic food or beverages of = 40 g pure ethanol per day

22. subjects who are on a diet which could affect the pharmacokinetics of the active ingredient

23. regular intake of caffeine containing food or beverages of = 500 mg caffeine per day

24. blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the subject

25. administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject

26. regular treatment with any systemically available medication

27. subjects practising top-performance sports (more than 4 x 2 h per week)

28. subjects suspected or known not to follow instructions

29. 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

Related Conditions & MeSH terms

• Bioequivalence

Intervention

Drug:
• RID-TDS 9.5 mg/24 h
3 consecutive applications of 1 patch (1st patch for 4 days, 2nd patch for 3 days, 3rd patch for 4 days) covering an 11-day period
• Exelon® 9.5 mg/24 h
11 consecutive applications of 1 patch (each patch will be applied for 1 day) covering an 11-day period

Locations

Country	Name	City	State
Germany	SocraTec R&D GmbH, Clinical Pharmacology Unit	Erfurt	Thüringen

Sponsors (2)

Lead Sponsor	Collaborator
SocraTec R&D GmbH	SocraMetrics GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC96-264	partial area under the plasma concentration vs. time profile for the time interval 96-264 hours	from 96 to 264 hours after the first patch application
Primary	Cmax,96-264	maximum concentration in plasma during the nominal time interval 96-264 hours	from 96 to 264 hours after the first patch application
Primary	Cmin,96-264	absolute minimum concentration within the nominal time interval 96-264 hours	from 96 to 264 hours after the first patch application
Primary	Patch adhesion properties	lower one-sided 90% confidence limit for the mean of Test	at 96, 168 and 264 hours after the first Test patch application
Secondary	Skin irritation	frequency of scores for quantification of skin irritation per treatment and time point	from first patch removal until last patch removal (approx. 9 to 13 days)
Secondary	Adverse events	descriptive evaluation of frequency and intensity, relationship to the IMP, action taken, outcome, seriousness, period and treatment	approximately 7 to 12 weeks, through study completion in case of follow-up
Secondary	inhibition of plasma butyrylcholinesterase (BuChE)	% inhibition of BuChE activity in plasma in comparison to baseline	from first patch application until 24 hours after the last patch removal