Rivastigmine Transdermal Patches Bioequivalence and Adhesion Assessment

Bioequivalence and Adhesion Assessment Between Two Rivastigmine Transdermal Patch Formulations

This study evaluates the bioequivalence and adhesion performance of a test rivastigmine transdermal patch compared with the reference product, Exelon® Patch 10 (9.5 mg/24 h), in healthy adult volunteers of both sexes under fasting conditions. The pharmacokinetic profiles will be compared to assess whether the test product demonstrates equivalent rate and extent of absorption to the reference formulation. Patch adhesion will also be evaluated throughout the dosing interval to determine whether the test product shows high adhesion (>90%) or non-inferior adhesion compared with the reference product.

Study Overview

• Status: Completed
• Conditions: Bioequivalence Study in Healthy Subjects
• Intervention / Treatment: Drug: Rivastigmine TDS 9,5 mg/24 h; Drug: Exelon® 9.5 mg/24 h

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Goiás
    • Aparecida de Goiânia, Goiás, Brazil, 74935-530
      • Instituto de Ciências Farmacêuticas de Estudos e Pesquisas

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Body mass index (BMI) between 18.5 and 30.0 kg/m².
• Non-smokers or former smokers who stopped smoking at least 1 year prior to screening.
• Clinically healthy based on medical history, physical examination, vital signs, ECG, and clinical laboratory tests.
• Negative screening for HIV, hepatitis B, and hepatitis C.
• Female participants must not be pregnant or breastfeeding and must have a negative pregnancy test.
• No hair, wounds, or dermatological conditions at the intended patch application site (upper arm).
• Able to understand the study procedures and provide written informed consent

Exclusion Criteria:

• History or presence of clinically significant cardiovascular, hepatic, renal, gastrointestinal, neurological, psychiatric, metabolic, pulmonary, or dermatological diseases.
• Known hypersensitivity to rivastigmine, carbamate derivatives, or any component of the study formulation.
• Abnormal clinical laboratory results, vital signs, or ECG considered clinically significant by the investigator.
• Positive test results for drugs of abuse, alcohol misuse, HIV, hepatitis B, or hepatitis C.
• Use of prescription or non-prescription medications that could interfere with the study drug within a defined period prior to dosing, as determined by the investigator.
• Participation in another clinical trial or exposure to an investigational drug within the previous 6 months.
• Blood donation or significant blood loss within 3 months prior to the study.
• Consumption of grapefruit-containing products, alcohol, or substances that could interfere with drug metabolism prior to dosing.
• Use of medications known to significantly affect hepatic metabolism.
• Dermatological conditions or skin alterations that could interfere with patch adhesion or drug absorption.
• Positive or suspected infection with SARS-CoV-2 prior to study periods.
• Any condition that, in the investigator's judgment, could interfere with study participation or the interpretation of study results.

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: Test; Single application of the test rivastigmine transdermal patch (9.5 mg/24 h) for a 24-hour wear period.	Drug: Rivastigmine TDS 9,5 mg/24 h; Rivastigmine Transdermal Patch
Active Comparator: Comparator; Single application of the reference rivastigmine transdermal patch (Exelon® Patch 10, 9.5 mg/24 h) for a 24-hour wear period.	Drug: Exelon® 9.5 mg/24 h; Exelon Patch 10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed plasma concentration of rivastigmine following application of the transdermal patch.	Up to 48 hours after patch application
AUC0-t	Area under the plasma concentration-time curve from time zero to the last quantifiable concentration of rivastigmine.	Up to 48 hours after patch application
AUC0-12	Area under the plasma concentration-time curve of rivastigmine from time zero to 12 hours after patch application.	0 to 12 hours after patch application
AUC12-t	Area under the plasma concentration-time curve of rivastigmine from 12 hours to the last quantifiable concentration.	12 to 48 hours after patch application
Patch Adhesion	Percentage of the transdermal patch surface remaining adhered to the skin at the end of the 24-hour dosing interval.	24 hours after patch application

Collaborators and Investigators

• Sponsor: Zodiac Produtos Farmaceuticos S.A.

Publications and helpful links

General Publications

• BRASIL. AGÊNCIA NACIONAL DE VIGILÂNCIA SANITÁRIA. Resolução - RDC nº 742, de 10 de agosto de 2022. "DISPÕE SOBRE OS CRITÉRIOS PARA CONDUÇÃO DE ESTUDOS DE BIODISPONIBILIDADE RELATIVA/BIOEQUIVALÊNCIA (BD/BE) E ESTUDOS FARMACOCINÉTICOS". Diário Oficial da União, Brasília, 17 de agosto de 2022.
• Lefevre, G. et al. Pharmacokinetics and Bioavailability of the Novel Rivastigmine transdermal patch versus rivastigmine oral solution in healthy elderly subjects. J. Clin. Pharmacol., v. 48, p.246-252, 2008.
• Hossain, M. et al. Estimation of the Absolute Bioavailability of Rivastigmine in Patients with Mild to Moderate Dementia of the Alzheimer's Type. Clin Pharmacokinet, v. 41, n.3, p. 225-234, 2002.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2023
• Primary Completion (Actual): June 6, 2023
• Study Completion (Actual): July 3, 2023

Study Registration Dates

• First Submitted: March 6, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 11, 2026

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Carbamates; Phenylcarbamates; Rivastigmine
• Other Study ID Numbers: PBIO03222

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to confidentiality restrictions and institutional policies regarding participant-level clinical data.

Drug and device information, study documents

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