None listed
Conditions
Brief summary
This research project is being conducted to look at the adhesion, Pharmacokinetics (PK, how the human body processes a substance), safety and tolerability of formulations of Corplex ('Trademarked') Donepezil TDS (Transdermal Delivery System) when applied to healthy volunteers for seven days. It is anticipated that Corplex ('Trademarked') Donepezil TDS could be a treatment for Alzheimer's Disease.
Interventions
TDS Main Study
Treatment A: Corplex ('Trademarked') Donepezil TDS (10 mg/day target dose), 105 cm2 active drug/skin contact area with 0.5 cm adhesive edge applied and worn for seven days.
Treatment B: Corplex ('Trademarked') Donepezil TDS (10 mg/day target dose), 105 cm2 active drug/skin contact area with 1.0 cm adhesive edge applied and worn for seven days.
Treatment E: Corplex ('Trademarked') Donepezil TDS, with adhesive overlay Type II (10 mg/day target dose), 120 150 cm2 active drug/skin con
TDS Main Study Treatment A: Corplex ('Trademarked') Donepezil TDS (10 mg/day target dose), 105 cm2 active drug/skin contact area with 0.5 cm adhesive edge applied and worn for seven days. Treatment B: Corplex ('Trademarked') Donepezil TDS (10 mg/day target dose), 105 cm2 active drug/skin contact area with 1.0 cm adhesive edge applied and worn for seven days. Treatment E: Corplex ('Trademarked') Donepezil TDS, with adhesive overlay Type II (10 mg/day target dose), 120 150 cm2 active drug/skin contact area with 1.0 cm adhesive edge applied and worn for seven days. Treatment F: Corplex ('Trademarked') Donepezil TDS with adhesive overlay Type III (10 mg/day target dose), 120 150 cm2 active drug/skin contact area with 1.0 cm adhesive edge applied and worn for seven days. Treatment G: Corplex ('Trademarked') Donepezil TDS with adhesive overlay Type IV (10 mg/day target dose) 120 150 cm2 active drug/skin contact area with 1.0 cm adhesive edge applied and worn for seven days. All formulations will be applied as one patch worn continuously for seven days, applied to the lower back (preferred location is vertically along the spine) by a trained member of site staff. Participants will remain in the study facility for the duration of patch application and will be constantly monitored to ensure compliance. 50% of the Treatment E, F or G subjects will be permitted to shower or bathe as long as the application site is not immersed or does not have consistent and constant contact with water such as water spraying over the patch application site (occasional splashes of small amounts of water are acceptable but should be avoided). Subjects will be asked to try to avoid splashing water on or allowing running water to contact the patch application area. A shower shield is not to be worn over the patch while showering. Subjects will be required to shower 1 to 2 hours prior to TDS application on Day 8. Subjects should avoid scrubbing or rubbing the potential application area and should not use soaps or lotions. The potential application area should be patted dry after the shower. On subsequent days, showers should occur following the first PK draws and 6 hours prior to the last PK draw of the day (on days where there is more than one PK draw). On Day 15 showers are restricted to 1 to 2 hours prior to TDS removal or after the skin residue sample is collected. The other 50% of the Treatment E, F or G Subjects will be permitted to shower or bathe providing the application site is not immersed and water is not directed immediately on the patch application site ; however water running down on the patch application site, and water splashing on the patch site is acceptable. A subject will be assigned to one of the shower methods based on subject order of enrollment and gender (example: first female and first male subject qualified for the study will be assigned to have a restricted shower and 2nd female and male screen will be assigned to have a flexible shower). Treatment C: Lead-in Dose – 5 mg donepezil hydrochloride (Aricept, 'Registered Trademark'), as daily oral dose, for seven days, will be used as a lead-in dose in the treatment period. Aricept ('Registered Trademark') will be given to all participants as a 5 mg oral tablet once daily for the seven days prior to patch application. Participants will be administered the first dose of Aricept ('Registered Trademark') in the study facility, and this will be documented on an accountability log kept at site. Site staff will instruct participants to retain the empty drug bottles to return to site at Day 7. When participants return to site on Day 7, site staff will check the number of empty drug bottles to ensure compliance. In addition to this, site staff will be making daily phone calls to participants who will be completing the lead-in doses at home to perform AE checks and compliance check to Aricept. This will be documented in subject source notes. Oral sub-study (to commence after TDS Main Study): Treatment C: Lead-in Dose – 5 mg donepezil hydrochloride (Aricept, 'Registered Trademark'), as daily oral dose, for seven days, will be used as a lead-in dose in the treatment period. Treatment D: 10 mg donepezil hydrochloride (Aricept, 'Registered Trademark'), as daily oral dose, for seven days, commenced after the lead-in dose with Treatment C. Aricept ('Registered Trademark') will be given to all participants as a 5 mg oral tablet once daily for the seven days prior to commencement of 10mg Aricept ('Registered Trademark') dosing. Participants will be administered the first dose of 5mg Aricept ('Registered Trademark') in the study facility, and this will be documented on an accountability log kept at site. Site staff will instruct participants to retain the empty drug bottles to return to site at Day 7. When participants return to site on Day 7, site staff will check the number of empty drug bottles to ensure compliance. In addition to this, site staff will be making daily phone calls to participants who will be completing the lead-in doses at home to perform AE checks and compliance check to 5mg Aricept. This will be documented in subject source notes.
Sponsors
INCResearch Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
50 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in the TDS Main Study and Oral Sub-Study. 1. Caucasian male or female aged 50 to 80 years (inclusive) on Day 1. 2. Has a Body Mass Index between 18-32 kg/m2 (inclusive) as calculated using the site standard procedures. 3. Must be willing and able to understand and participate in all scheduled evaluations by providing a signed and dated written informed consent prior to the initiation of any study procedures. 4. Women and men of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Postmenopausal status will be verified by the absence of the menstrual cycle for twelve consecutive months or medical documentation of an oophorectomy or hysterectomy or bilateral tubal ligation and follicle-stimulating hormone (FSH) blood test at screening (FSH must be > 25.8 mIU/mL). Subjects on stable doses of hormone replacement therapy who have an FSH level < 25.8 mIU/mL can be enrolled at the Investigator's discretion. 5. If the subject is receiving allowed medications for the treatment of non-excluded medical conditions, the dose must be stable for at least 14 days or 5 half-lives (whichever is longer) before Day 1. Permitted medications must be consistent with the current label for oral donepezil (Aricept 'Registered Trademark') tablets.
Exclusion criteria
Participants who meet any of the following exclusion criteria will be excluded from participation in the TDS Main Study. Participants who meet any of the following exclusion criteria that are applicable to the Oral Sub-study will be excluded from participation in the sub-study. 1. Dosing with an Investigational Product not containing donepezil within 60 days prior to screening. 2. Plasma donation within 28 days of screening or any blood donation or blood loss greater than 500 mL within three months of screening. 3. Has skin color or tone that may not allow reliable evaluation of irritation. (Applicable to the TDS Main Study only) 4. Unwilling to abstain from new strenuous physical exercise and from alcohol consumption for 48 hours prior to scheduled PK blood draws at the clinic visits (subjects can maintain their normal exercise routine). 5. Has intolerance to venipuncture and/or inability to comply with the extensive blood sampling required for this study or does not have suitable veins in both arms. 6. Has cuts, scratches/abrasions, scars, breaks in the skin surface, recent tattoos (within last six months) at the TDS application site, skin with excessive hair, indications of sunburn, excessive skin tanning, stretch marks and/or similar abnormalities at the intended TDS application sites which would affect absorption of donepezil. (Applicable to the TDS Main Study only). 7. Unwilling to avoid using tanning salons, saunas, or sun bathing during the conduct of the study. Unwilling to avoid shaving of the TDS application site, waxing of the TDS application site, or use of lotion hair remover on or near the TDS application site from 48 hours before patch application and during the conduct of the study. (Applicable to the TDS Main Study only). 8. Unwilling to abstain from food or beverages containing grapefruit, starfruit, pomegranate, limes, seville oranges, pomelo and food or beverages containing greater than 5% of the aforementioned fruits (examples are: fruit drinks, fruit punches, fruit cocktails, fruit aides) 14 days prior to the first dose and throughout the study. 9. Subjects with a history of or who are currently consuming high caffeine levels (greater than ten regular or espresso cups of coffee per day); heavy smokers who smoke more than 20 cigarettes per day. Exception will be made for lighter smokers and subjects on stable doses of nicotine patches. 10. Presence of any major psychiatric disorder if, in the opinion of the Investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect/tolerability, or affect the subject’s ability to complete the study. 11. Significant cardiovascular disease, including moderate or severe congestive heart failure (ejection fraction of less than 40%) or clinically significant stenosis or occlusion of a carotid or vertebral artery. 12. Significant or chronic lung disease, including Chronic Obstructive Pulmonary Disease and severe or unstable asthma. 13. Diabetes complicated with retinopathy (by history), neuropathy (by history or physical examination), or nephropathy (by history). Uncomplicated, stable diabetes that is well controlled and actively managed is not exclusionary. 14. Known or suspected systemic infection, including human immunodeficiency virus, hepatitis B virus or hepatitis C virus, or tuberculosis or qualitative syphilis test as judged by the Investigator at screening. 15. History of severe allergy/hypersensitivity reactions or ongoing allergy/hypersensitivity reactions, or history of hypersensitivity to donepezil, piperidine derivatives or other drugs of the cholinesterase inhibitor class. 16. Potential for occupational exposure to anticholinesterase agents in the three weeks prior to Day 1 or prior to the planned Study Exit Visit 17. History of cancer within five years of screening or between screening and Day 1, with the exception of non-metastatic, treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or non-progressive prostate cancer. 18. Transient Ischemic Attack or stroke in the last three years. 19. History of suspected alcohol or drug dependence within two years of screening, or positive urine drug test at the screening visit or positive urine drug test one day before investigational product administration (with the exception of nicotine dependence, which is permitted). 20. Myocardial infarction, hospitalization for unstable angina or arrhythmia or unexplained syncope within one year of screening. 21. Clinically important infection, including chronic, persistent or acute infection, within three months of screening or between screening and Day 1. 22. Any medical or surgical procedure or trauma within 28 days of Day 1. 23. Current serious or unstable clinically important illness, including avascular necrosis, respiratory, cardiovascular, gastrointestinal, endocrinologic, immunologic, hematologic or other major disease that is likely to deteriorate or affect the subject’s safety or ability to complete the study, as judged by the Investigator. 24. Exhibiting symptoms suggestive of bladder outflow obstruction as determined by the Investigator. 25. Have a history of allergic reactions to medical grade adhesive tapes, sunscreens, cosmetics, lotions, fragrances, or latex. C. Concomitant Medications and Procedural Contraindications 26. Use of any nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 analgesic therapy, 30 days prior to Day 1 and until completion of the Study Exit Visit. This includes over-the-counter pain medications and topical analgesics that contain a NSAID or COX-2. The use of NSAIDs or COX-2 medications at any time during the study and through to completion of the Study Exit Visit is prohibited and contraindicated. 27. Use of the follow medications within 30 days prior to Day 1 and until completion of the Study Exit Visit: - Beta-blockers; - Anti-fungal medications; - Anti-histamines; - Cholinergics and anti-cholinergics; - Oral corticosteroids; - Prolia (a monoclonal antibody therapy used in the treatment of osteoporosis); - Antidepressants, including tricyclics, tetracyclics, selective serotonin re-uptake inhibitors and serotonin-norepinephrine re-uptake inhibitors - Anticonvulsants - Use of muscle relaxants, anti-Parkinsonian or neuroleptic medications 28. Use of any topical medication in the areas intended for TDS patch application within 14 days prior to patch application and throughout the study; (Applicable to the TDS Main Study only) 29. Use of any topical products without medicinal ingredient (including but not limited to perfumes, body lotions, sunscreens, spray or patch oils, creams and alcohol) on the area intended for TDS patch application within 48 hours prior to the patch application until after the last sample collection of the TDS treatment period. Topical application of products without significant systemic absorption are allowed in areas other than the ones intended for patch application; (Applicable to the TDS Main Study only) 30. Irregular use of herbal or dietary supplements, or commencement of a new herbal or dietary supplement within seven days prior to the first dose and throughout the study. 31. Use of St. John’s Wort within 28 days prior to the first dose and throughout the study. 32. Use of food or beverages containing xanthine derivatives, xanthine-related compounds and/or energy drinks from 48 hours prior to the first dose. 33. Use of donepezil HCl (including Corplex ('Trademarked') Donepezil TDS) and related drugs within 14 days of dosing. 34. Clinically important abnormality in physical examination, vital signs or clinical laboratory test at screening that could affect the subject’s safety or ability to complete the study, as judged by the Investigator. 35. Clinically significant hypertension defined as systolic blood pressure of greater than 160 mmHg and/or diastolic blood pressure of greater than 95 mmHg. Out-of-range results can be confirmed with a double repeat to determine eligibility. 36. Any clinically significant abnormality in ECG rhythm, conduction or morphology, including but not limited to: - Clinically significant PR (PQ) interval prolongation (PR greater than 220 ms); - Intermittent second or third degree atrioventricular (AV) block (AV block II Mobitz Type I, Wenckebach, while asleep or in deep rest is not exclusionary); - Incomplete, full or intermittent bundle branch block (QRS less than 115 msec with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy); - Abnormal T wave morphology suggesting ischemic heart disease; - Prolonged QTcF of greater than 470 msec or family history of long QT syndrome, or shortened QTcF of less than 360 msec or family history of short QT syndrome. 37. Aspartate transaminase or alanine transaminase levels greater than 1.5 upper limit of normal at screening, or between screening and baseline. 38. Screening creatinine clearance of less than 50 mL/min as determined by the Cockcroft-Gault formula. 39. Clinically significant abnormal findings in laboratory tests of coagulation, or hematology or a screening hemoglobin value of less than 113 g/L. 40. A positive pregnancy test at screening or between screening and Day 8 (fertile females only). 41. Positive urine drug screen for drugs of abuse (list as per protocol) unless there is documentation that the subject has been prescribed the corresponding medication and the medication is otherwise acceptable for the study. 42. Heart rate less than or equal to 50 bpm.
Outcome results
None listed