Safety and pharmacokinetics of the orally available antiprionic compound PRI‐002: A single and multiple ascending dose phase I study

INTRODUCTION: PRI‐002 is an orally available anti–amyloid beta (Aβ) prionic compound developed for direct disassembly of toxic Aβ oligomers relevant to Alzheimer's disease. METHODS: Two placebo‐controlled clinical phase I trials with oral dosing of PRI‐002 were conducted in healthy young subjects: A single ascending dose trial (4, 12, 36, 108, or 320 mg PRI‐002 or placebo) in 40 participants followed by a multiple ascending dose study with daily 160 mg PRI‐002 for 14 days or 320 mg for 28 days in 24 participants. The main objectives were safety, tolerability, and evaluation of pharmacokinetic (PK) parameters. RESULTS: PRI‐002 was safe and well tolerated after single and multiple oral administration up to the highest doses. PRI‐002 was absorbed rapidly and drug exposure increased proportional to dose. During repeated daily administration, the drug accumulated by a factor of about three. Steady‐state conditions were reached after 1 to 2 weeks. CONCLUSIONS: The safety and PK results encourage further clinical development of PRI‐002.