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

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ClinicalTrials.gov Identifier: NCT03573050
Recruitment Status : Completed
First Posted : June 29, 2018
Last Update Posted : August 21, 2018
Sponsor:
Collaborator:
SocraMetrics GmbH
Information provided by (Responsible Party):
SocraTec R&D GmbH

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.

Condition or disease Intervention/treatment Phase
Bioequivalence Drug: RIV-TDS 13.3 mg/24 h Drug: Exelon® 13.3 mg/24 hours transdermal patch Phase 1

Detailed Description:

This will be a single centre, open-label, randomised (order of treatments), balanced, 2-period, 2-sequence, cross-over trial with multiple applications of rivastigmine transdermal patches. There will be no wash-out, i.e. the first investigational patch application of the second study period will take place the day of the last investigational patch removal of the first study period (direct switch-over).

Prior to start of first treatment, there will be an adaptation phase with 4 consecutive applications of Exelon® 9.5 mg/24 hours transdermal patch over a period of 4 days (each patch will be applied for 24 hours). Following the removal of the last investigational patch in period II, there will be a post-treatment tapering phase with 2 consecutive applications of Exelon® 9.5 mg/24 hours transdermal patch over a period of 2 days (each patch will be applied for 24 hours).

Furthermore, during the adaptation phase, both study periods and the tapering phase, scopolamine transdermal patches will be applied as co-medication to attenuate effects of rivastigmine and reduce Adverse Events.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Multiple Dose Crossover Comparative Bioavailability Study of a Transdermal Patch Formulation of Rivastigmine Compared With Exelon® Transdermal Patch With a Release Rate of 13.3 mg/24 Hours in Healthy Male Subjects With Preceding Adaptation Phase and Post-treatment Tapering Phase
Actual Study Start Date : May 16, 2018
Actual Primary Completion Date : July 5, 2018
Actual Study Completion Date : July 5, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: RIV-TDS 13.3 mg/24 h (Test)
5 consecutive patch applications of Test (each patch to be applied for 24 hours)
Drug: RIV-TDS 13.3 mg/24 h
5 consecutive transdermal patch applications, each with a nominal release rate of 13.3 mg/24 hours

Active Comparator: Exelon® 13.3 mg/24 hours transdermal patch (Reference)
5 consecutive patch applications of Reference (each patch to be applied for 24 hours)
Drug: Exelon® 13.3 mg/24 hours transdermal patch
5 consecutive transdermal patch applications, each with a nominal release rate of 13.3 mg/24 hours




Primary Outcome Measures :
  1. AUC0-tau,ss [ Time Frame: from 0 to 24 hours following the 5th patch application ]
    Area under the plasma concentration vs. time curve at steady state for rivastigmine

  2. Ctau,ss [ Time Frame: from 0 to 24 hours following the 5th patch application ]
    (Trough) minimum plasma concentration at the end of the dosing interval at steady state for rivastigmine

  3. Cmax,ss [ Time Frame: from 0 to 24 hours following the 5th patch application ]
    Maximum plasma concentration within the dosing interval at steady state for rivastigmine


Secondary Outcome Measures :
  1. Patch adhesion [ Time Frame: from first investigational patch application until removal of the last investigational patch (approx. 10 days) ]
    one-sided lower 90% confidence limit of mean adherence percentage at the end of the dosing interval of the 5th patch

  2. Skin irritation [ Time Frame: from first investigational patch removal until last investigational patch removal (approx. 10 days) ]
    frequency of scores for quantification of skin irritation per treatment and time point

  3. Adverse events [ Time Frame: approximately 2 weeks, through study completion in case of follow-up ]
    descriptive evaluation of frequency and intensity, relationship to the IMP, action taken, outcome, seriousness, period and treatment



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Sex: male
  2. Ethnic origin: Caucasian
  3. Age: 18 - 50 years, inclusive
  4. Body-mass index2 (BMI): >=18.5 kg/m² and <= 30.0 kg/m²
  5. Good state of health
  6. Non-smoker or ex-smoker for at least 6 months
  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 ingredients (especially sick sinus syndrome or conduction defects such as sino-atrial block, atrio-ventricular block, arrhythmia, bradycardia)
  2. 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))
  3. 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)
  4. History of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders (e.g. cerebral sclerosis)
  5. History of asthma or obstructive pulmonary disease
  6. Glaucoma or any indications from case history that there might be raised intra-ocular pressure (e.g. pressure pain, blurred vision, glaucomatous halo)
  7. 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
  8. Subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
  9. Body weight below 65 kg
  10. Systolic blood pressure < 90 or ≥ 140 mmHg
  11. Diastolic blood pressure < 60 or >90 mmHg
  12. Heart rate < 60 bpm or > 90 bpm
  13. QTc interval > 450 ms
  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. 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 scopolamine or rivastigmine patches based on assessment of the investigator
  18. Skin abnormality (e.g. tattoo or scar) at the application site
  19. Acute or chronic diseases which may interfere with the pharmacokinetics of scopolamine or rivastigmine patches
  20. History of or current drug or alcohol dependence
  21. Positive alcohol or drug test at screening examination
  22. Regular intake of alcoholic food or beverages of ≥ 40 g pure ethanol per day
  23. Subjects who are on a diet which could affect the pharmacokinetics of the active ingredients
  24. Regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day
  25. Blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the subject
  26. Administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject
  27. Regular treatment with any systemically available medication
  28. Subjects practising top-performance sports (more than 4 x 2 h per week)
  29. Subjects suspected or known not to follow instructions
  30. 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 -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03573050


Locations
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Germany
SocraTec R&D GmbH, Clinical Pharmacology Unit
Erfurt, Thüringen, Germany, 99084
Sponsors and Collaborators
SocraTec R&D GmbH
SocraMetrics GmbH

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Responsible Party: SocraTec R&D GmbH
ClinicalTrials.gov Identifier: NCT03573050     History of Changes
Other Study ID Numbers: 1351riv18ct
2018‐000968‐28 ( EudraCT Number )
C_30170_P1_16 ( Other Identifier: Luye Pharma AG / Luye Supply AG )
First Posted: June 29, 2018    Key Record Dates
Last Update Posted: August 21, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Rivastigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents