Rivastigmine Bioequivalence Trial With Multiple Application of Transdermal Patches (13.3mg/24h)

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 13.3 mg/24 h (Twice-weekly Patch) Compared to the Reference Exelon® 13.3 mg/24 h (Once-daily Patch) Applied for 11 Days

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 13.3 mg/24 h (Luye Pharma AG, Germany) and the marketed Reference product Exelon® 13.3 mg/24 h transdermales Pflaster (Novartis Pharma GmbH, Germany) after multiple patch applications. Each of both treatments will last for 11 days with a washout period of 14 days between the treatments.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: RID-TDS 13.3 mg/24 h; Drug: Exelon® 13.3 mg/24 h

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Thüringen
    • Erfurt, Thüringen, Germany, 99084
      • SocraTec R&D GmbH, Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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. body weight >= 65 kg
5. 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
6. non-smoker or ex-smoker for at least 1 month
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 ingredient (especially sick sinus syndrome or conduction defects such as sino-atrial block, atrio-ventricular block (second degree or higher)) or concomitant treatment with beta-blockers
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 or subjects suffering from overactive bladder treated with anticholinergics)
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, e.g. depression treated with tricyclic antidepressants, or psychosis treated with neuroleptics (cave! Metoclopramide), Parkinson's disease and predisposition to seizures
5. history of chronic obstructive or other pulmonary diseases or bronchial asthma
6. acute or history of narrow-angle glaucoma, currently treated open-angle glaucoma, or any indications from case history that there might be raised intra-ocular pressure (e.g. pressure pain, blurred vision, glaucomatous halo)
7. subjects suffering from pyloric stenosis or having difficulty in passing water owing to an impeded flow of urine (e.g. in diseases of the prostate), as well as subjects with intestinal obstruction, arrhythmia, pronounced bradycardia and severe cerebral sclerosis as well as metabolic diseases
8. 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 or scopolamine patch
9. history of severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
10. systolic blood pressure < 90 or > 139 mmHg
11. diastolic blood pressure < 60 or > 89 mmHg
12. heart rate < 50 bpm or > 90 bpm
13. QTc interval > 450 ms (according to Fridericia formula)
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. diagnosis of COVID-19 and/or persisting disease symptoms (e.g., fever, cough) at the Investigator's discretion; current state or federal COVID-19 regulations will be considered.
18. participation in a clinical trial with administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject
19. simultaneous participation in another clinical trial with active ingredients Lack of suitability for the clinical trial
20. 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 or NIMP based on assessment of the investigator
21. skin abnormality (e.g. tattoo or scar) at the application site
22. acute or chronic diseases which may interfere with the pharmacokinetics of the IMP
23. history of or current drug or alcohol dependence
24. positive alcohol or drug test at screening examination
25. regular intake of alcoholic food or beverages of ≥ 24 g pure ethanol per day
26. subjects who are on a diet which could affect the pharmacokinetics of the active ingredient
27. regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day
28. blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the subject
29. regular treatment with any systemically available medication (except replacement therapy, e.g. L-thyroxine)
30. subjects practising top-performance sports (more than 4 x 2h per week) Administrative reasons
31. close affiliation with the sponsor or the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee of or student at the investigational site), employee of the sponsor or affiliates
32. subjects suspected or known not to follow instructions
33. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RID-TDS 13.3 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	Drug: RID-TDS 13.3 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
Active Comparator: Exelon® 13.3 mg/24 h; 11 consecutive applications of 1 patch (each patch will be applied for 1 day) covering an 11-day period	Drug: Exelon® 13.3 mg/24 h; 11 consecutive applications of 1 patch (each patch will be applied for 1 day) covering an 11-day period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Cmax96-264	maximum concentration in plasma during the nominal time interval 96-264 hours	from 96 to 264 hours after the first patch application
Ctau264	trough concentration at the planned time point 264 h p.a.	264 hours after the first patch application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.
• Collaborators: SocraTec R&D GmbH; SocraMetrics GmbH
• Investigators: Principal Investigator: Juliane Koerner, MD, SocraTec R&D GmbH

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2023
• Primary Completion (Actual): July 2, 2023
• Study Completion (Actual): July 17, 2023

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Cholinesterase Inhibitors; Rivastigmine
• Other Study ID Numbers: C_30410_P1_08; 2022-003718-35 (EudraCT Number); 1428riv22ct (Other Identifier: SocraTec R&D GmbH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No