None listed
Conditions
Brief summary
This is a Phase 1, open-label, cross-over, randomized, study in healthy subjects conducted in two parts. Part A of the study is a three-way cross-over, partially randomized (for the first two treatment periods) design to evaluate the PK, safety, tolerability and PD of donepezil administered from two different formulations of a TDS (Donepezil TDS LF 50 cm2 and Donepezil TDS HF 50 cm2) compared to oral donepezil (Aricept). Part B of the study is a two-way cross-over, randomized design to evaluate the adhesive properties, safety, tolerability and PK of a larger donepezil TDS (either Donepezil TDS LF 150cm2 or Donepezil TDS HF 100cm2) with two different backing laminate compositions.
Interventions
This is a Phase 1, open-label, cross-over, randomized study in healthy subjects conducted in two parts. Part A of the study is a three-way cross-over, partially randomized (for the first two treatment periods) design to evaluate the PK, safety, tolerability and pharmacodynamics (PD) of two different formulations of donepezil administered from a TDS (Donepezil TDS LF 50 cm2 and Donepezil TDS HF 50 cm2) compared to oral donepezil (Aricept) in healthy subjects. Part B of the study is a two-way cros
This is a Phase 1, open-label, cross-over, randomized study in healthy subjects conducted in two parts. Part A of the study is a three-way cross-over, partially randomized (for the first two treatment periods) design to evaluate the PK, safety, tolerability and pharmacodynamics (PD) of two different formulations of donepezil administered from a TDS (Donepezil TDS LF 50 cm2 and Donepezil TDS HF 50 cm2) compared to oral donepezil (Aricept) in healthy subjects. Part B of the study is a two-way cross-over, randomized design to evaluate the adhesive properties, safety, tolerability and PK of a larger patch size donepezil TDS (either Donepezil TDS LF 150cm2 or Donepezil TDS HF 100cm2) with two different backing laminate compositions. Part A The following treatments will be administered in Part A of the study: Treatment A: Donepezil TDS LF 50 cm2 patch: 3 x 50 cm2 patches will be applied (total application area of 150 cm2) and worn for seven days, target dose 10 mg/day. An overlay will be applied to the patches. Treatment B: Donepezil TDS HF 50 cm2 patch: 2 x 50 cm2 patches will be applied (total application area of 100 cm2) and worn for seven days, target dose 10 mg/day. An overlay will be applied to the patches. Treatment C: Comparator – donepezil hydrochloride 10 mg (Aricept), as a daily oral dose for seven days. A washout of at least 15 days between each treatment is allowed. Part B Part B will commence after at least the first six subjects have completed Day 11 of Treatment Period 1 in Part A. The TDS formulations to be assessed in this part of the study will be selected by the sponsor following review of the safety and PK data from the first six subjects in Part A. Based on these results either the two TDS LF or the two TDS HF formulations listed below will be administered in Part B of the study: Treatment D1: Donepezil TDS LF 150 cm2 patch with backing formulation 1: 1 x 150 cm2 patch will be applied and worn for seven days, target dose 10 mg/day. Treatment D2: Donepezil TDS LF 150 cm2 patch with backing formulation 2: 1 x 150 cm2 patch will be applied and worn for seven days, target dose 10 mg/day. Or Treatment E1: Donepezil TDS HF 100 cm2 patch with backing formulation 1: 1 x 100 cm2 patch will be applied and worn for seven days, target dose 10mg/day. Treatment E1: Donepezil TDS HF 100 cm2 patch with backing formulation 2: 1 x 100 cm2 patch will be applied and worn for seven days, target dose 10mg/day. There is a wash-out period of 10 days before starting the second period in Part B. A new set of participants will be recruited for Part B Part A – Treatments A and B The following two transdermal patch formulations are being compared in Part A of this study: Donepezil TDS LF 50 cm2 (Treatment A) and Donepezil TDS HF 50 cm2 (Treatment B). Each formulation contains 90 mg donepezil per patch. Both Treatment A and Treatment B are transdermal patch formulations consisting of three layers. These formulations differ from each other with respect to the composition of the middle drug–in-adhesive layer and the donepezil delivery is anticipated to be approximately 3-fold higher for Donepezil TDS HF when compared to the LF formulation. Part A Treatment C In Australia Aricept is marketed by Pfizer Australia Pty Ltd. It is indicated for the treatment of mild, moderate and severe Alzheimer’s disease. Donepezil hydrochloride 10 mg (Aricept), as an oral tablet, will be provided in bottles. The site pharmacy will dispense in a single use individualized dosing container according to the dosing schedule. Part B – Treatments D1, D2, E1, E2 The Donepezil TDS LF formulations to be evaluated in this part of the study have a patch size of 150 cm2 and contain 270 mg donepezil per patch. The Donepezil TDS HF formulations to be evaluated in this part of the study have a patch size of 100 cm2 and contain 180 mg donepezil per patch. The TDS LF and HF with backing formulation 1 (Treatments D1 and E1, respectively) are comprised of 5 layers and differ in composition from the Part A TDS treatments by the addition of a thin adhesive layer and a stretchable woven fabric between the top backing layer and the drug-in -adhesive layer. The TDS LF and HF with backing formulation 2 (Treatments D2 and E2, respectively) are comprised of 3 layers and differ in composition from the Part A TDS treatments by the addition of a stretchable woven fabric in the drug-in-adhesive layer. Patches will be applied across the back for both parts of the study.
Sponsors
INCResearch Australia Pty Ltd
Study design
Allocation
Randomised controlled 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
- Has a Body Mass Index (BMI) between 18-32 kg/m2 (inclusive) as calculated using the site standard procedures. - Willing and able to discontinue all nonsteroidal anti-inflammatory drugs (NSAID) or COX-2 analgesic therapy, thirty days prior to Day 1 and until completion of the Study Exit Visit. This includes over-the-counter (OTC) pain medications and topical analgesics that contain an 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. - If the subject is receiving allowed medications for the treatment of non-excluded medical conditions, the dose must be stable for at least twenty eight days before randomization on Day 1. Permitted medications must be consistent with the current label for oral donepezil (Aricept) tablets. - 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 ninety 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.
Exclusion criteria
- Plasma donation within twenty eight days of screening or any blood donation or blood loss > 500 mL within three months of screening. - Unwilling to abstain from new strenuous physical exercise and from alcohol consumption for forty eight hours prior to scheduled PK blood draws at the clinic visits (subjects can maintain their normal exercise routine). - Has cuts, scratches/abrasions, scars, breaks in the skin surface, recent tattoos (within last six months) at the application site, skin with excessive hair, indications of sunburn, excessive skin tanning, stretch marks and/or similar abnormalities at the intended application sites which would affect absorption of the Investigational Product. - Must refrain from using tanning salons, saunas, or sun bathing during the conduct of the study. Must also avoid shaving of application site, waxing of application site, or use of lotion hair remover on or near application site from 48 hours before patch application and during the conduct of the study. - Must abstain from food or beverages containing grapefruit, starfruit, pomegranate, limes, seville oranges, pomelo and food or beverages containing > 5% the aforementioned fruits (examples are: fruit drinks, fruit punches, fruit cocktails, fruit aides) fourteen days prior to the first patch application and throughout the study. - Has a history of or is currently consuming high caffeine levels (greater than ten regular or espresso cups of coffee per day) and/or smoke more than twenty cigarettes per day for more than ten years (ex-smokers can be included in the study if they ceased smoking at least one year from the start of the study) - Significant cardiovascular disease, including moderate or severe congestive heart failure (ejection fraction of < 40%) or clinically significant stenosis or occlusion of a carotid or vertebral artery - Diabetes complicated with retinopathy (by history), neuropathy (by history or physical examination), or nephropathy (by serum creatinine > ULN or proteinuria > 0.2 g/L). Uncomplicated, stable diabetes that is well controlled and actively managed is not exclusionary. - Potential for occupational exposure to anticholinesterase agents in the three weeks prior to randomization or prior to the planned Study Exit Visit - Have a history of allergic reactions to medical grade adhesive tapes, sunscreens, cosmetics, lotions, fragrances, or latex. - Use of adjuvant analgesics, including antidepressants, anticonvulsants, selective serotonin re-uptake inhibitors (SSRIs) and serotonin-norepinephrine re-uptake inhibitors (SNRIs). The use of antidepressant therapy for depressive illness is permitted if judged to be clinically acceptable by the Investigator. - 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 patch application within forty eight hours prior to the first patch application until after the last sample collection of each period. Topical application of products without significant systemic absorption are allowed in areas other than the ones intended for patch application - Use of food or beverages containing xanthine derivatives, xanthine-related compounds and/or energy drinks from forty eight hours prior to each patch application until after the last pharmacokinetic blood sample of each treatment period
Outcome results
None listed