A Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TPI-287 in Alzheimer's Disease

Exclusion Criteria

• •7. Has a reliable study partner who agrees to accompany the subject to visits, and spends at least 5 hours per week with the subject
• •8. Agrees to 2 lumbar punctures
• •9. Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations
• •10. Males and all WCBP agree to abstain from sex or use an adequate method of contraception for the duration of the study and for 30 days after the last dose of study drug.
• •1. Any medical condition other than AD that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia)
• •2. History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof)
• •3. History of significant peripheral neuropathy
• •4. History of major psychiatric illness or untreated depression
• •5. Neutrophil count \<1,500/mm3, platelets \<100,000/mm3, serum creatinine \>1.5 x upper limit of normal (ULN), total bilirubin \>1.5 x ULN, alanine aminotransferase (ALT) \>3 x ULN, aspartate aminotransferase (AST) \>3 x ULN, or INR \>1.2 at Screening or baseline evaluations
• •6. Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of study data
• •7. Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection
• •8. Current clinically significant viral infection
• •9. Major surgery within four weeks prior to Screening
• •10. Unable to tolerate MRI scan at Screening
• •11. Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening
• •12. Subjects who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule or study evaluations
• •13. Any previous exposure to microtubule inhibitors (including TPI 287) within 5 years of Screening. Treatment with microtubule inhibitors other than TPI287 while on study will not be allowed
• •14. Participation in another AD clinical trial within 3 months of Screening
• •15. Treatment with another investigational drug within 30 days of Screening. Treatment with investigational drugs other than TPI 287 while on study will not be allowed
• •16. Known hypersensitivity to the inactive ingredients in the study drug
• •17. Pregnant or lactating
• •18. Positive pregnancy test at Screening or Baseline (Day 1)
• •19. Cancer within 5 years of Screening, except for non-metastatic skin cancer.