Age-Associated Memory Impairment (AAMI) MedDRA version: 9.1 Level: LLT Classification code 10027175 Term: Memory impairment
Conditions
Interventions
Product Name: LX6171 40 mg/ml
Product Code: LX6171 40 mg/ml
Pharmaceutical Form: Oral suspension
Current Sponsor code: LX6171
Other descriptive name: LP-512064, ((3'-chlorobiphenyl-4-yl) (1-(pyrimidin
Sponsors
Lexicon Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Stage A of the study: - Males or females 60-80 years old; - Females must be post-menopausal (defined as two years without menses) or surgically sterile (defined by surgical sterilization, hysterectomy or bilateral salpingo-oophorectomy); - Vital signs (after at least 3 minutes resting in a supine position) which are within the following ranges or considered not clinically significant if outside these ranges: - Systolic blood pressure, 100-140 mmHg - Diastolic blood pressure, 60-100 mmHg - Heart rate, 60-100 bpm - Non-smokers or very light smokers (less than or equal to 10 cigarettes per day) who are able to abstain from smoking during the residential part of the study; - Body weight between 50 and 100 kg and body mass index (BMI) between 18 and 30 kg/m2 or, if outside the range, not clinically significant and agreed with Sponsor and Investigator; - Negative urine screen for drugs of abuse at screening and on the day of admission (Day 1); - Negative hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), and HIV 1 and HIV 2 antibody test results must be obtained within the last 21 days prior to study admission; - Ability to provide written, informed consent. Stage B of the study: - Adult males and females 60-80 years (inclusive) old; - Females must be post-menopausal (defined as two years without menses) or surgically sterile (defined by surgical sterilization, hysterectomy or bilateral salpingo-oophorectomy); - Complaints of memory loss in everyday life as reflected by a score of 25 or more on the Memory Complaint Questionnaire (MAC-Q); - Memory test performance of one standard deviation below the mean established for young adults on the Logical Memory I Subtest of the Wechsler Memory Scale-Revised (WMS-R) , but not more than a standard deviation below the age-adjusted mean on the test (score of 11 to 19, inclusive); - Vital signs (after at least 3 minutes resting in a supine position) which are within the following ranges or considered not clinically significant if outside these ranges: o Systolic blood pressure, 100-140 mmHg o Diastolic blood pressure, 60-100 mmHg o Heart rate, 60-100 bpm - Body weight between 50 and 100 kg and BMI between 18 and 30 kg/m2 or, if outside the range, not clinically significant and agreed with Sponsor and Investigator; - Negative urine screen for drugs of abuse at screening; - Negative hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), and HIV 1 and HIV 2 antibody test results must be obtained within the last 28 days prior to study admission; - Non-smokers or very light smokers (less than or equal to 10 cigarettes per day) who are able to abstain from smoking during the residential part of the study - Ability to provide written, informed consent; Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Stage A of the study: - A need for or having taken any medication within 21 days of dosing, with the exception of hormone replacement therapy, ibuprofen and paracetamol; - Administration of any investigational agent within 12 weeks of study entry; - Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the absorption, distribution, metabolism, or excretion of LX6171; - Clinically significant abnormal physical findings; - Clinically significant laboratory abnormality; - Clinically significant abnormalities on resting Electrocardiogram (ECG); - Donation or loss of greater than 400 mL of blood within 12 weeks of study entry; - Serious adverse reaction or hypersensitivity to any drug; - Known history of hepatic disease or significantly abnormal liver function tests (greater than 1.5 times the upper limit of normal) on study entry; - History of alcoholism or substance abuse within three years prior to study entry; - Known history of significant hematological abnormalities; - Concurrent conditions that could interfere with the safety and/or tolerability measurements; - Inability to communicate or cooperate with the study staff for any reason Stage B of the study: - Any neurological disorder that could produce cognitive deterioration as determined by history, clinical neurological examination, and, if indicated neuroradiologic examinations. Such disorders include Alzheimer’s Disease, Mild Cognitive Impairment, Parkinson's disease, stroke, intracranial hemorrhage, local brain lesions including tumors, and normal pressure hydrocephalus; - History of any infective or inflammatory brain disease, including those of viral, fungal, or syphilitic etiologies; - Evidence of dementia as determined by a score of 26 or less on a Mini-Mental State Examination (MMSE); - Evidence of depression as determined by a score of 11 or higher on the Geriatric Depression Scale (GDS); - Evidence of delirium, confusion, or other disturbances of consciousness; - Clinically significant cardiovascular, hepatic, renal, endocrine, neurological, or psychiatric disorders that could be responsible for memory loss in the judgment of the investigator; - Current psychiatric diagnosis according to DSM-IV criteria of depression, mania, or any major psychiatric disorder; - Evidence of significant cerebral vascular pathology as determined by a Hachinski Ischemic Score of 4 or more, or by neuroradiologic examination; - History of repeated minor head injury (e.g. in boxing) or a single injury resulting in a period of unconsciousness for 20 minutes or more; - Baseline laboratory values indicative of clinically significant co morbidity; - History of myocardial infarction within the past 12 months or evidence of recent infarction on ECG; - Current diagnosis or history of alcoholism or drug dependence, and not able/willing to commit to alcohol restrictions; - A need for having taken any medication within 21 days of dosing, with the exception ofhormone replacement therapy, ibuprofen, paracetamol, daily vitamins and aspirin; - Use of dietary supplements containing Huperzine A, gingko biloba, phosfatidylserine or docosahexanoic acid (DHA) within 15 days of baseline evaluation or reasonably expected to use these supplements during the course of the study are not eligible to participate. - Administration of any investigational agent within 12 weeks of study entry; - Donation or loss of greater than 400 mL of blood within 12 weeks of stu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In stage A, the primary objective is: - To compare the relative bioavailability of a single dose of 300 mg LX6171 using a 40mg/mL and an 80mg/mL formulated suspension; - To evaluate plasma concentrations of LX6171 and its major metabolite LP-523122 after a single 300 mg administration of LX6171 oral suspension at two concentrations (40 mg/mL and 80 mg/mL), in order to determine doses to be utilized over a 28 day period (see stage B). In stage B, the primary objective is: - To evaluate the safety and tolerability of 2 dose levels LX6171 oral suspension when administered for 28 days, in subjects exhibiting AAMI;Secondary Objective: In stage A, the secondary objective is: - To evaluate the safety and tolerability of single doses of 300 mg of LX6171 utilizing two different concentrations of oral suspension (40 mg/mL and 80 mg/mL) in healthy elderly subjects In stage B, the secondary objective is: - To evaluate effects of multiple doses of LX6171 oral suspension on cognition in subjects exhibiting AAMI; - To evaluate plasma concentrations of LX6171 and its major metabolite LP-523122 after administration of LX6171 oral suspension for 28 days, in subjects exhibiting AAMI;Primary end point(s): Stage A and B: - pharmacokinetic characteristics - safety and tolerability Stage B: Weekly cognition will be assessed using the following instruments: - A standardized, validated cognitive assessment battery from Cognitive Drug Research (CDR) - Memory Assessment Clinics Self-Rating Scale (MAC-S) - Rey Auditory Verbal Learning Test (RAVLT) - One-Week Delayed Recall Test (OWDRT) | — |
Countries
Netherlands
Outcome results
None listed