Rivastigmine BA Trial With Multiple Application of Transdermal Patches, Adaptation and Tapering Phase

NCT03573050 | Completed Phase 1

• 3 other identifiers: 1351riv18ct2018-000968-28C_30170_P1_16
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (3)

• AUC0-tau,ss

  Area under the plasma concentration vs. time curve at steady state for rivastigmine

  from 0 to 24 hours following the 5th patch application

• Ctau,ss

  (Trough) minimum plasma concentration at the end of the dosing interval at steady state for rivastigmine

  from 0 to 24 hours following the 5th patch application

• Cmax,ss

  Maximum plasma concentration within the dosing interval at steady state for rivastigmine

  from 0 to 24 hours following the 5th patch application

Secondary Outcomes (3)

• Patch adhesion

  from first investigational patch application until removal of the last investigational patch (approx. 10 days)

• Skin irritation

  from first investigational patch removal until last investigational patch removal (approx. 10 days)

• Adverse events

  approximately 2 weeks, through study completion in case of follow-up

Study Arms (2)

RIV-TDS 13.3 mg/24 h (Test)

EXPERIMENTAL

5 consecutive patch applications of Test (each patch to be applied for 24 hours)

Drug: RIV-TDS 13.3 mg/24 h

Exelon® 13.3 mg/24 hours transdermal patch (Reference)

ACTIVE COMPARATOR

5 consecutive patch applications of Reference (each patch to be applied for 24 hours)

Drug: Exelon® 13.3 mg/24 hours transdermal patch

Interventions

RIV-TDS 13.3 mg/24 h DRUG

5 consecutive transdermal patch applications, each with a nominal release rate of 13.3 mg/24 hours

RIV-TDS 13.3 mg/24 h (Test)

Exelon® 13.3 mg/24 hours transdermal patch DRUG

5 consecutive transdermal patch applications, each with a nominal release rate of 13.3 mg/24 hours

Exelon® 13.3 mg/24 hours transdermal patch (Reference)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sex: male
• Ethnic origin: Caucasian
• Age: 18 - 50 years, inclusive
• Body-mass index2 (BMI): \>=18.5 kg/m² and \<= 30.0 kg/m²
• Good state of health
• Non-smoker or ex-smoker for at least 6 months
• 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 ingredients (especially sick sinus syndrome or conduction defects such as sino-atrial block, atrio-ventricular block, arrhythmia, bradycardia)
• 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))
• 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)
• History of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders (e.g. cerebral sclerosis)
• History of asthma or obstructive pulmonary disease
• Glaucoma or any indications from case history that there might be raised intra-ocular pressure (e.g. pressure pain, blurred vision, glaucomatous halo)
• 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
• Subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
• Body weight below 65 kg
• Systolic blood pressure \< 90 or ≥ 140 mmHg
• Diastolic blood pressure \< 60 or \>90 mmHg
• Heart rate \< 60 bpm or \> 90 bpm
• QTc interval \> 450 ms
• 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
• SocraMetrics GmbH: collaborator

Study Sites (1)

SocraTec R&D GmbH, Clinical Pharmacology Unit

Erfurt, Thuringia, 99084, Germany

Location

Related Publications (1)

• Morte A, Vaque A, Iniesta M, Schug B, Koch C, De la Torre R, Schurad B. Bioavailability Study of a Transdermal Patch Formulation of Rivastigmine Compared with Exelon in Healthy Subjects. Eur J Drug Metab Pharmacokinet. 2022 Jul;47(4):567-578. doi: 10.1007/s13318-022-00778-5. Epub 2022 Jun 13.

  PMID: 35696054 DERIVED

MeSH Terms

Interventions

Rivastigmine; Transdermal Patch

Intervention Hierarchy (Ancestors)

Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Equipment and Supplies

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 22, 2018
• First Posted: June 29, 2018
• Study Start: May 16, 2018
• Primary Completion: July 5, 2018
• Study Completion: July 5, 2018
• Last Updated: August 21, 2018

Record last verified: 2018-08

Locations

DE (1)