Dementia and Alzheimer's Disease
Conditions
Interventions
Memogain will be administered intranasally for 7 days b.i.d. (14 doses in
total). The 12 subjects from cohort 2 that were on Memogain treatment will be
administered galantamine 16 mg once, as well a
Sponsors
NEURODYN LIFE SCIENCES INC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male or postmenopausal female subjects, aged 65 years and over. Healthy status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), haematology, blood chemistry, and urinalysis; 2. Body Mass Index (BMI) between 18 kg/m² and 30 kg/m², inclusive, and with a minimum weight of 50 kg; 3. Able to participate and willing to give written informed consent and to comply with the study restrictions; 4. Absence of cognitive impairment evident by a score of 26 or higher on the Mini Mental State Examination (MMSE); 5. Non-smokers.
Exclusion criteria
Exclusion criteria: 1. Legal incapacity or inability to understand or comply with the requirements of the study; 2. Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history taking and physical examinations obtained during the screening visit and/or at the start of the first study day for each period as judged by the investigator; 3. Any disease associated with cognitive impairment, including (but not restricted to) schizophrenia and dementia; 4. Clinically relevant abnormal laboratory results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), electrocardiogram (ECG) and vital signs, or physical findings at screening and/or at the start of the first study day for each period (as judged by the investigator). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects; 5. Systolic blood pressure (SBP) greater than 145 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg; 6. Notable resting bradycardia (HR 100 bpm) at screening or baseline visit; 7. Male: QtcF >450 or 460 or 1.5 times the upper limit of normal at screening; 15. Evidence of significant renal insufficiency, indicated by a glomerular filtration rate lower than the lower limit of normal (related to age) at screening; 16. Concomitant use of cholinergic (e.g. varenicline, donepezil, rivastigmine) or anti-cholinergic (e.g. clozapine, olanzapine) medication within 21 days prior to dosing; 17. Concomitant use of inhibitors or inducers of CYP2D6 (e.g., kinidine, paroxetine, fluoxetine) or of CYP3A4 (e.g., ketoconazol, ritonavir) within 21 days prior to dosing; 18. Subject is unable to refrain f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability / safety endpoints • Treatment-emergent (serious) adverse events ((S)AEs) up to 5 pharmacokinetic half-lives after study drug (i.e. Memogain) discontinuation. • Treatment-emergent abnormalities in vital signs (blood pressure and pulse rate) until end of study (EOS). • Treatment-emergent marked ECG abnormalities up to 5 pharmacokinetic half-lives after study drug discontinuation (i.e. Memogain). • Treatment-emergent marked laboratory abnormalities up to 5 pharmacokinetic half-lives after study drug discontinuation (i.e. Memogain). • The above 4 endpoints will also be investigated after galantamine administration in cohort 2 • Post-dose nasal examinations. Pharmacokinetic endpoints PK model A population PK model will be developed to describe the pharmacokinetic profile of Memogain and galantamine in plasma. The estimated population values of the model parameters (both fixed and random effects) are used to determine individual empirical Bayes' estimates of the primary pharmacokinetic parameters such as CL/F, V/F and Vss/F, and of derived observable parameters including, but not limited to, Cmax, tmax, AUC-0-, and apparent terminal half-life. Additional PK parameters may be calculated if appropriate. CSF To investigate possible differences between concentration of galantamine cleaved from Memogain and concentrations of galantamine following oral administration in the central nervous system, CSF galantamine and Memogain concentrations will be compared within-subject in cohort 2 (Memogain 11mg). 12 subjects that were on active treatment in cohort 2 will be randomized to one of four different CSF sampling time points (i.e. 3 subjects per time point). In total, two CSF samples will be taken per subject (one after Memogain administration on Day 1, and one after galantamine oral administration) to characterise the time-concentration curve for Memogain and galantamine. PK/PD relationship The relationship between plasma Memogain and | — |
Countries
Netherlands
Outcome results
None listed