Multiple Ascending Dose Study of TC-5619 in Elderly Subjects With Alzheimer's Disease
This is a Phase 1, multi-center, study design that will examine the safety, tolerability, maximum tolerated dose, and pharmacokinetics of TC-5619-238 in elderly subjects with and without Alzheimer's Disease.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Diagnostic
|Official Title:||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|
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Group 1: screening, Days -14, Day -1, Days 1, 2, 3, 27-33; Group 2: Day -14, Day -1, Days 1 -14 ] [ Designated as safety issue: Yes ]Number of participants with treatment-emergent adverse events
- Pharmacokinetic profiles [ Time Frame: Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14 ] [ Designated as safety issue: Yes ]Plasma concentrations (pharmacokinetic profiles) of TC-5619-238 over time (Groups 1 & 2) and urine (Group 2) samples after multipe doses
- Markers of inflammation in cerebrospinal fluid [ Time Frame: Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14 ] [ Designated as safety issue: No ]Changes in markers of inflammation in cerebrospinal fluid (Group 1 only)
- Markers of inflammation in plasma [ Time Frame: Group 1: Days 1, 2, 28-32; Group 2: Day 1, 2, 4, 8, 10-14 ] [ Designated as safety issue: No ]Dose related changes in markers of inflammation in plasma over time (Groups 1 & 2)
|Study Start Date:||September 2010|
|Study Completion Date:||May 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
Supplied as a blend of API with excipients in a hard gelatin capsule (gelatin and titanium dioxide). Excipients used are microcrystalline cellulose, colloidal silicon dixoide, croscarmellose sodium, and magnesium stearate.
Active Comparator: TC-5619-238
TC-5619-238 (tosylate sale) will be provided as a 25mg dose strength in hard gelatin capsules.
TC-5619-238 is supplied as a blend of active pharmaceutical ingredient (API) with excipients in a hard gelatin capsule (gelatin and titanium dioxide). Excipients used are microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, and magnesium stearate.
This is a multi-center study design to establish the safety, tolerability, maximum tolerated dose, and pharmacokinetics of the alpha-7 receptor agonist TC-5619-238 in elderly subjects with Alzheimer's Disease. In addition, the study may provide preliminary evidence supporting the potential therapeutic benefits of using TC-5619-238 in subjects with Alzheimer's Disease, including modulation of systemic- and neuro-inflammation.
30 subjects (20 active, 10 placebo) w/Alzheimer's Disease will receive 28 days of dosing with 25mg of TC-5619-238 or placebo. Subjects will have an initial 3-day in-clinic assessment, followed by 23 days of out-patient treatment, and a final in-clinic assessment period of 6 days. CSF and plasma collection pre-dose on Days 1 and 28, PK will be collected on Days -1, 1, 2, 28-32.
Group 2 (without Alzheimer's Disease): First cohort will receive a daily dose of 50mg or matching placebo. Cohorts 2 and 3 will receive doses of 100mg and 150mg (or matching placebo), respectively. Subjects will have a screening period (Days -14 to -1), 11 days of in-clinic dosing (Days -1 to Day 10), 4 days in-clinic post-treatment follow-up (Days 11-14) and 1 day end-of-study safety assessment (Day 15). Each cohort will include 6 elderly subjects on active treatment and 2 elderly subjects on placebo treatment. Cohort dose escalation to next highest dose will occur after a safety assessment of tolerability for the cohort, plus a preliminary PK assessment on half of the treated subjects. Plasma collection pre-dose on Days 1, 2, 4, 8, and 10-14.
|United States, California|
|Collaborative Neuroscience Network|
|Long Beach, California, United States, 90806|
|San Francisco Clinical Research Center|
|San Francisco, California, United States, 94109|
|United States, Florida|
|Hallandale Beach, Florida, United States, 33009|
|Miami Springs, Florida, United States, 33166|
|Comprehensive Phase One|
|Miramar, Florida, United States, 333025|
|Compass Research, LLC|
|Orlando, Florida, United States, 32806|
|United States, Georgia|
|Atlanta Center For Clinical Research|
|Atlanta, Georgia, United States, 30308|
|United States, New Jersey|
|Princeton Medical Institutes|
|Princeton, New Jersey, United States, 08540|
|United States, Texas|
|Community Clinical Research|
|Austin, Texas, United States, 78754|
|United States, Utah|
|Aspen Clinical Research|
|Orem, Utah, United States, 84058|
|Principal Investigator:||George Gerson, MD||Comprehensive Phase One|