阿茲海默病

The primary objective of this study is to establish bioequivalence (BE) in extent of exposure between 45 mg Donepezil “T.B.C.” (two patches of 22.5 cm2 patch, each contains 22.5 mg donepezil) and 5 mg donepezil (ARICEPT® as the reference) film-coated tablet in healthy volunteers based on systemic exposure using area under the plasma concentration-time curve (AUC) of one 4-day dosing interval of patch at steady state (AUC0,ss,patch) comparing to 4 times of daily AUC of oral 5 mg donepezil at steady state (AUC0,ss,oral). The secondary objectives of this study are: 1. To determine PK parameters for both the parent drug and its major active metabolite (6-O-desmethyl donepezil) of 45 mg Donepezil “T.B.C” (22.5 mg/patch*2) and ARICEPT®. 2. To evaluate the tolerability and safety of 45 mg Donepezil “T.B.C” (22.5 mg/patch* 2). 3. To evaluate adhesion performance of 45 mg Donepezil “T.B.C” (22.5 mg/patch*2).

Donepezil

45

The primary objective of this study is to establish bioequivalence (BE) in extent of exposure between 45 mg Donepezil “T.B.C.” (two patches of 22.5 cm2 patch, each contains 22.5 mg donepezil) and 5 mg donepezil (ARICEPT® as the reference) film-coated tablet in healthy volunteers based on systemic exposure using area under the plasma concentration-time curve (AUC) of one 4-day dosing interval of patch at steady state (AUCss,patch) comparing to 4 times of daily AUC of oral 5 mg donepezil at steady state (AUCss,oral).

1. Main inclusion criteria:
1. Males and non-pregnant females aged between ≧ 20 years and < 40 yearsold at the time of obtaining informed consent.
2. Subjects who have not been smoking for at least 4 weeks prior to study treatment.
3. Subjects agree not to apply creams, lotions, powders, or other topical products to the skin area where the patch will be placed.
4. Subjects whose body mass index (BMI) at screening is 18.5 kg/m2 or above and less than 25.0 kg/m2. BMI = Body Weight (kg) / [Height (m) x Height (m)]
5. Subjects who are willing and able to provide written informed consent by their own will.
6. Subjects who are judged to be in good health by the investigator based upon the results of physical examinations (PEs), medical history, and routine laboratory tests.
7. Subjects who are willing to and can comply with the conditions described in the study protocol.

2. Main exclusion criteria:
1. Subjects who are pregnant or lactating.
2. History of significant dermatologic cancers (e.g. melanoma, squamous cell carcinoma), significant dermatologic diseases/conditions (eg. atopy, psoriasis, vitiligo), or conditions known to alter skin appearance or physiologic response (eg. diabetes, porphyria).
3. Subjects with the following conditions at the application site(s) that would interfere with the placement of the patch, skin assessment, or reaction to drug:
a. presence of open sores.
b. obvious differences in skin color between applications sites.
c. excessive hair.
d. scar tissue tattoo.
e. coloration.
4. Any significant medical illness that required intervention within 8 weeks before treatment.
5. Subjects with any clinically significant infectious, psychiatric, gastrointestinal (GI) tract, hepatic, renal, respiratory, endocrine, hematological, neurological, cardiovascular diseases or congenital metabolic disorders within 4 weeks before study drug administration that may have an impact on the evaluation of the drug.
6. Subjects with any medical history of GI, hepatic, or renal surgery including but not limited to excision of liver, kidney or GI tract that may have an impact on pharmacokinetics of the drug.
7. Subjects who have any history of medically significant allergy to donepezil or any of the excipients in donepezil patch.
8. Subjects who have any history of allergy to foods.
9. Those with clinically abnormal symptoms, medical history of organ dysfunction, subjective symptoms, objective findings, vital signs, and abnormal electrocardiogram (ECG) or clinical laboratory test values, which need medical intervention.
10. Corrected QT wave (QTc) interval of > 450 msec with 12-lead ECG at screening.
11. Subjects who are carriers of Hepatitis B virus, Hepatitis C virus, or are syphilis (STS) positive, or human immunodeficiency virus (HIV) positive.
12. Subjects who are suspected with or who has a history of drug or alcohol abuse or dependence according to DSM IV criteria at screening.
13. Subjects who consumed caffeine-containing food or beverages within 72 hours before study drug administration.
14. Exposure to any supplements or herbs (including Chinese medicine), or beverages containing alcohol or grapefruit, within 2 weeks of study drug administration.
15. Exposure to St. John’s wort containing medications within 4 weeks of study drug administration.
16. Use of any prescription drugs within 4 week before study drug administration.
17. Use of any OTC medications within 2 week before study drug administration.
18. Subjects who enrolled in another clinical trial and exposed to any investigational drug within 16 weeks of study enrollment.
19. Subject had blood donation below 250 ml within 60 days or over 250 ml within 90 days prior to the first dose of the study.
20. If a subject is of child-bearing potential, she must be practicing sexual abstinence or be using and willing to continue to use a medically acceptable form of birth control for at least 1 month prior to screening (that period will extend to 3 months for oral contraceptive use) and for at least 60 days after the last dose of study drug. For a subject to be considered not to be of child-bearing potential, she must have been amenorrheic for at least 2 years, or must have had a hysterectomy, a bilateral tubal ligation, and/or a bilateral oophorectomy (as determined by the medical history). A male study subject with a female partner of childbearing potential must use a condom and ensure that his partner uses a suitable method of contraception as outlined above.
21. Subjects who are inappropriate to participate in the study, as judged by the investigator or sub-investigator.

1. Main inclusion criteria:
1. Males and non-pregnant females aged between ≧ 20 years and < 40 yearsold at the time of obtaining informed consent.
2. Subjects who have not been smoking for at least 4 weeks prior to study treatment.
3. Subjects agree not to apply creams, lotions, powders, or other topical products to the skin area where the patch will be placed.
4. Subjects whose body mass index (BMI) at screening is 18.5 kg/m2 or above and less than 25.0 kg/m2. BMI = Body Weight (kg) / [Height (m) x Height (m)]
5. Subjects who are willing and able to provide written informed consent by their own will.
6. Subjects who are judged to be in good health by the investigator based upon the results of physical examinations (PEs), medical history, and routine laboratory tests.
7. Subjects who are willing to and can comply with the conditions described in the study protocol.

2. Main exclusion criteria:
1. Subjects who are pregnant or lactating.
2. History of significant dermatologic cancers (e.g. melanoma, squamous cell carcinoma), significant dermatologic diseases/conditions (eg. atopy, psoriasis, vitiligo), or conditions known to alter skin appearance or physiologic response (eg. diabetes, porphyria).
3. Subjects with the following conditions at the application site(s) that would interfere with the placement of the patch, skin assessment, or reaction to drug:
a. presence of open sores.
b. obvious differences in skin color between applications sites.
c. excessive hair.
d. scar tissue tattoo.
e. coloration.
4. Any significant medical illness that required intervention within 8 weeks before treatment.
5. Subjects with any clinically significant infectious, psychiatric, gastrointestinal (GI) tract, hepatic, renal, respiratory, endocrine, hematological, neurological, cardiovascular diseases or congenital metabolic disorders within 4 weeks before study drug administration that may have an impact on the evaluation of the drug.
6. Subjects with any medical history of GI, hepatic, or renal surgery including but not limited to excision of liver, kidney or GI tract that may have an impact on pharmacokinetics of the drug.
7. Subjects who have any history of medically significant allergy to donepezil or any of the excipients in donepezil patch.
8. Subjects who have any history of allergy to foods.
9. Those with clinically abnormal symptoms, medical history of organ dysfunction, subjective symptoms, objective findings, vital signs, and abnormal electrocardiogram (ECG) or clinical laboratory test values, which need medical intervention.
10. Corrected QT wave (QTc) interval of > 450 msec with 12-lead ECG at screening.
11. Subjects who are carriers of Hepatitis B virus, Hepatitis C virus, or are syphilis (STS) positive, or human immunodeficiency virus (HIV) positive.
12. Subjects who are suspected with or who has a history of drug or alcohol abuse or dependence according to DSM IV criteria at screening.
13. Subjects who consumed caffeine-containing food or beverages within 72 hours before study drug administration.
14. Exposure to any supplements or herbs (including Chinese medicine), or beverages containing alcohol or grapefruit, within 2 weeks of study drug administration.
15. Exposure to St. John’s wort containing medications within 4 weeks of study drug administration.
16. Use of any prescription drugs within 4 week before study drug administration.
17. Use of any OTC medications within 2 week before study drug administration.
18. Subjects who enrolled in another clinical trial and exposed to any investigational drug within 16 weeks of study enrollment.
19. Subject had blood donation below 250 ml within 60 days or over 250 ml within 90 days prior to the first dose of the study.
20. If a subject is of child-bearing potential, she must be practicing sexual abstinence or be using and willing to continue to use a medically acceptable form of birth control for at least 1 month prior to screening (that period will extend to 3 months for oral contraceptive use) and for at least 60 days after the last dose of study drug. For a subject to be considered not to be of child-bearing potential, she must have been amenorrheic for at least 2 years, or must have had a hysterectomy, a bilateral tubal ligation, and/or a bilateral oophorectomy (as determined by the medical history). A male study subject with a female partner of childbearing potential must use a condom and ensure that his partner uses a suitable method of contraception as outlined above.
21. Subjects who are inappropriate to participate in the study, as judged by the investigator or sub-investigator.