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

NCT05883124 | Completed Phase 1

• 2 other identifiers: 1429riv22ct2023-000074-10
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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 marketed Test product Rivastigmine twice-weekly 9,5 mg/24 h transdermal patch (Manufacturer: Luye Pharma AG, Germany) and the marketed Reference product Exelon® 9.5 mg/24 h transdermal patch (Manufacturer: LTS Lohmann Therapie-Systeme AG, Germany) after multiple patch applications. Each of both treatments will last for 11 days with a washout period of at least 14 treatment-free days between the treatments.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (4)

• AUC96-264

  Partial area under the plasma concentration vs. time profile for the time interval 96 h 264 h

  From 96 to 264 hours after the first IMP application

• Cmax,96-264

  Maximum concentration in plasma during the nominal time interval 96 h-264 h, obtained directly from measured values

  From 96 to 264 hours after the first IMP application

• CTau264

  (Absolute) minimum concentration within the nominal time interval 96 h-264 h, obtained directly from measured values

  From 96 to 264 hours after the first IMP application

• 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 Outcomes (1)

• Adverse events

  From 1st IMP application until individual discharge of a subject from the clinical trial, assessed up to approximately 2 months

Study Arms (2)

Rivastigmine twice-weekly 9,5 mg/24 h

EXPERIMENTAL

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: Rivastigmine twice-weekly 9,5 mg/24 h

Exelon® 9.5 mg/24 h

ACTIVE COMPARATOR

11 consecutive applications of 1 patch (each patch will be applied for 1 day) covering an 11-day period

Drug: Exelon® 9.5 mg/24 h

Interventions

Rivastigmine twice-weekly 9,5 mg/24 h DRUG

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

Rivastigmine twice-weekly 9,5 mg/24 h

Exelon® 9.5 mg/24 h DRUG

11 consecutive applications of 1 patch (each patch will be applied for 1 day) covering an 11-day period

Exelon® 9.5 mg/24 h

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• sex: male
• age: 18-55 years, inclusive
• body-mass index (BMI): ≥ 18.5 kg/m² and ≤ 30.0 kg/m²
• body weight ≥ 55 kg
• 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
• non-smoker or ex-smoker for at least 1 month
• 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

You may not qualify if:

• 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 β-blockers
• 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)
• 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)
• 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
• history of chronic obstructive or other pulmonary diseases or bronchial asthma
• 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)
• 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
• 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
• history of severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
• systolic blood pressure \< 90 or \> 139 mmHg
• diastolic blood pressure \< 60 or \> 89 mmHg
• heart rate \< 50 bpm or \> 90 bpm
• QTc interval \> 450 ms (according to Fridericia formula)
• laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator
• 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).

Sponsors & Collaborators

• SocraTec R&D GmbH: lead

Study Sites (1)

SocraTec R&D GmbH, Clinical Pharmacology Unit

Erfurt, Thuringia, 99084, Germany

Location

MeSH Terms

Interventions

Rivastigmine

Intervention Hierarchy (Ancestors)

Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Koerner

  SocraTec R&D GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2023
• First Posted: May 31, 2023
• Study Start: April 17, 2023
• Primary Completion: June 19, 2023
• Study Completion: July 21, 2023
• Last Updated: February 2, 2024

Record last verified: 2024-02

Locations

DE (1)