Multiple Ascending Dose Study of TC-5619 in Healthy Elderly Subjects and Subjects With Alzheimer's Disease

Study Overview
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Brief Summary
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This is a Phase 1 study to examine the safety, tolerability and pharmacokinetics of TC-5619 in elderly subjects with and without Alzheimer's disease. Group 1 includes elderly subjects with Alzheimer's disease to receive TC-5619 or placebo for 28 days to evaluate safety and tolerability. Group 2 includes healthy elderly subjects in a dose escalation design to receive TC-5619 or placebo for 10 days to evaluate safety, tolerability and pharmacokinetics.

Official Title
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Two-Part, Sequential Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TC-5619-238 in Elderly Subjects With and Without Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: TC-5619
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Groups 1 & 2): Normal body mass index (BMI) Non-smoking for a minimum of 3 months Subjects must be in reasonably good health, based on medical history, physical examination, vital signs, and ECG. Group 1 Only: Subjects a Mini Mental State Examination score between 12-22, inclusive. Diagnosis of probable Alzheimer's Disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria Subjects must have a reliable caregiver. Exclusion Criteria (Groups 1 & 2): Subjects with clinically significant heart disease, pulmonary disease, diabetes, neurologic or psychiatric disease (Group 1 subjects must have Alzheimer's Disease), or any other illness that could interfere with interpretation of study results. Subjects with a past or current history of seizures cannot participate. Current use of donepezil, rivastigmine or galantamine.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects will receive a placebo capsule orally once a day for 28 days (Group 1) or 10 days (Group 2). | Drug: Placebo<br>* Group 1: matching placebo administered once daily for 28 days. Group 2: matching placebo administered once daily for 10 days.<br>|
| Experimental: TC-5619<br>Subjects will receive a TC-5619 orally once a day for 28 days (Group 1) or 10 days (Group 2). | Drug: TC-5619<br>* Group 1: 25 mg TC-5619 administered once daily for 28 days. Group 2: 50-150 mg TC-5619 administered once daily for 10 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Number of participants with treatment-emergent adverse events | Group 1: screening, Days -14, Day -1, Days 1, 2, 3, 27-33; Group 2: Day -14, Day -1, Days 1 -14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profiles | Plasma concentrations (pharmacokinetic profiles) of TC-5619-238 over time (Groups 1 & 2) and urine (Group 2) samples after multiple doses | Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14 | 
| Markers of inflammation in cerebrospinal fluid | Changes in markers of inflammation in cerebrospinal fluid (Group 1 only) | Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14 | 
| Markers of inflammation in plasma | Dose related changes in markers of inflammation in plasma over time (Groups 1 & 2) | Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease