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

NCT03659435 | Completed Phase 1

• 3 other identifiers: 1352riv18ct2018-001570-18C_30410_P1_05
• Study Type: interventional
• Target: 58
• 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 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.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• Cmin,96-264

  absolute minimum concentration within the nominal time interval 96-264 hours

  from 96 to 264 hours after the first patch 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 (3)

• Skin irritation

  from first patch removal until last patch removal (approx. 9 to 13 days)

• Adverse events

  approximately 7 to 12 weeks, through study completion in case of follow-up

• inhibition of plasma butyrylcholinesterase (BuChE)

  from first patch application until 24 hours after the last patch removal

Study Arms (2)

RID-TDS 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: RID-TDS 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

RID-TDS 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

RID-TDS 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 index2 (BMI): ≥18.5 kg/m² and ≤ 30.0 kg/m²
• 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)
• 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)
• 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
• Subjects with chronic obstructive or other pulmonary diseases or bronchial asthma
• 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
• subjects with 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
• body weight below 50 kg
• 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).
• positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test or anti-HCV-test

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

MeSH Terms

Interventions

Rivastigmine

Intervention Hierarchy (Ancestors)

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

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: August 28, 2018
• First Posted: September 6, 2018
• Study Start: August 22, 2018
• Primary Completion: November 28, 2018
• Study Completion: November 28, 2018
• Last Updated: September 19, 2019

Record last verified: 2019-09

Locations

DE (1)