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.
Keywords: Alzheimer´s disease (AD); MAD; PRI‐002; SAD; anti‐Aβ‐prionic; first‐in‐human (FIH); multiple ascending dose; pharmacokinetics; phase I; safety; single ascending dose.
© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.