None listed
Conditions
Brief summary
This research project is being conducted to look at evaluate the Pharmacokinetics (PK) and Safety of Two Formulations of a 7-Day Application of Memantine Transdermal Delivery System (TDS) Compared to Oral Administration of NAMENDA XR and to assess TDS adhesion in Healthy 50-80 year old Volunteers
Interventions
Part A
Treatment A: Formulation A - Memantine TDS 362, 50 cm2 22 mg/day target dose (comprising three x patches for a total application area of 150 cm2) worn for seven days, four or three days.
Treatment B: Formulation B - Memantine TDS 360, 50 cm2 18 mg/day target dose (comprising three x patches for a total application area of 150 cm2) worn for seven days.
Treatment C: Comparator – (Memantine Hydrochloride) 28 mg (NAMENDA XR), as a daily oral dose for seven days.
Part B
Treatment D1: Memantine
Part A Treatment A: Formulation A - Memantine TDS 362, 50 cm2 22 mg/day target dose (comprising three x patches for a total application area of 150 cm2) worn for seven days, four or three days. Treatment B: Formulation B - Memantine TDS 360, 50 cm2 18 mg/day target dose (comprising three x patches for a total application area of 150 cm2) worn for seven days. Treatment C: Comparator – (Memantine Hydrochloride) 28 mg (NAMENDA XR), as a daily oral dose for seven days. Part B Treatment D1: Memantine TDS 362 with backing laminate 1, 150 cm2 22 mg/day target dose (comprising one x patch, total application area 150 cm2) worn for three days. There will be a washout period of ast least 15 days between treatments. (Monitoring to adherence not required since the IP is a patch formulation). Patch is applied to the backs of subjects Part C Treatment D1: Memantine TDS 362 with backing laminate 1, 150 cm2 22 mg/day target dose will be applied to the back and worn for three days. The patch will be removed on Day 4. A new Memantine TDS 362 treatment will be applied to the opposite side of the previous patch and will be worn for seven days. Part D Treatment D1: Memantine TDS 362 with backing laminate 1, 150 cm2 22 mg/day target dose worn for seven days
Sponsors
Corium International, Inc.
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
50 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Part A and B - Inclusion Criteria A. General * Caucasian male or female with light/pale skin aged 50 to 80 years (inclusive) on the day of randomization. * Has a Body Mass Index (BMI) between 18-34 kg/m^2 (inclusive) as calculated using the site standard procedures. * 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. B. Contraception and Concomitant Medications * 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. * If the subject is receiving allowed medications for the treatment of non-excluded medical conditions, must be stable for at least 28 days before randomization on Day 1. Any medications not at stable dose for at least 28 days, must be discontinued with a 5 x half-life washout and Sponsor approval prior to randomization on Day 1. Permitted medications must be consistent with the current label for oral Memantine (Namenda XR) tablets. * Negative 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.
Exclusion criteria
Exclusion Criteria A .General * Participation in another clinical study with an investigational product or device within sixty days prior to screening. * Plasma donation within 28 days of screening or any blood donation or blood loss greater than 500 mL within three months of screening. * Has skin color or tone that may not allow reliable evaluation of irritation. * Unwilling to abstain from strenuous physical exercise and from alcohol consumption for forty eight hours prior to scheduled PK blood draws at the clinic visits. * 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. * 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, moles and/or similar abnormalities at the intended application sites which would affect absorption of the Investigational Product. * Unwilling to refrain from using tanning salons, saunas, or sunbathe during the conduct of the study. Unwilling to also refrain from shaving of application site, waxing of application site, or using lotion hair remover on or near application site from twenty one days before patch application and during the conduct of the study. * Smoke more than twenty cigarettes per day B. Medical History * 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. * 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. * Significant or chronic lung disease, including Chronic Obstructive Pulmonary Disease (COPD) and severe or unstable asthma. * Diabetes complicated with retinopathy (by history), neuropathy (by history or physical examination), or nephropathy (by serum creatinine greater than ULN or proteinuria greater than0.2 g/L). Uncomplicated, stable diabetes that is well controlled and actively managed is not exclusionary. * Known or suspected systemic infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV), or tuberculosis (TB) or qualitative syphilis test as judged by the Investigator at screening. * History of severe allergy/hypersensitivity reactions or on-going allergy/hypersensitivity reactions, or history of hypersensitivity to Memantine or other drugs of the N-methyl-D-aspartate (NMDA) antagonist class. * History of cancer within five years of screening or between screening and randomization. Subjects with history of non-metastatic basal cell carcinoma of the skin, carcinoma in situ of the cervix or non-progressive prostate cancer may be enrolled with prior approval from Corium. * Transient Ischemic Attack (TIA) or stroke in the last three years. * History of suspected alcohol or drug dependence within two years of screening, or who are positive for urine drug test at the screening or one day before investigational product administration (with the exception of nicotine dependence, which is permitted). * Myocardial infarction, hospitalization for unstable angina or arrhythmia or unexplained syncope within one year of screening. * Clinically important infection, including chronic, persistent or acute infection, within three months of screening or between screening and randomization. * Any medical or surgical procedure or trauma within 28 days of Day 1. * 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. * Exhibiting symptoms suggestive of bladder outflow obstruction as determined by the Investigator. * Have a history of allergy or sensitivity or hypersensitivity to the ingredients in the TDS patches including glues/adhesives, topical alcohol, medical grade adhesive tapes, sunscreens, cosmetics, lotions, fragrances, and/or latex, which in the opinion of the Principal Investigator, would compromise the safety of the subject or the study. C. Concomitant Medications and Procedural Contraindications * Use of any topical medication in the areas intended for patch application within fourteen days prior to the first patch application and throughout the study; * Use of any topical products with or without medicinal ingredient (including but not limited to perfumes, body lotions, sunscreens, spray or patch oils, creams and alcohol) on the back 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; * Prior or current use of Memantine hydrochloride or to piperidine derivatives and related drugs (not applicable to Part A subjects returning for Part C) D. Physical Examination, Vital Signs, ECG, Laboratories and Imaging. * 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. * 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 used to determine eligibility. * 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 greater 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 450 msec (males), greater than 470 msec (females) or family history of long QT syndrome, or shortened QTcF of less than 360 msec or family history of short QT syndrome. * AST (aspartate transaminase) of ALT (alanine transaminase) levels greater than 1.5 ULN at screening, or between screening and baseline. * Screening creatinine clearance of less than 50 mL/min as determined by the Cockcroft-Gault formula. * Clinically significant abnormal findings in laboratory tests of coagulation, or hematology or has a screening hemoglobin value of less than 113 g/L. * A positive pregnancy test at screening or between screening and randomization (fertile females only). * Heart rate equal to 50 bpm
Outcome results
None listed