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

This title appears in the Scientific Report : 2020

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

IntroductionPRI‐002 is an orally available anti–amyloid beta (Aβ) prionic compound developed for direct disassembly of toxic Aβ oligomers relevant to Alzheimer's disease.MethodsTwo placebo‐controlled clinical phase I trials with oral dosing of PRI‐002 were conducted in healthy young subjects: A...

Personal Name(s):	Kutzsche, Janine
	Jürgens, Dagmar / Willuweit, Antje / Adermann, Knut / Fuchs, Carola / Simons, Stefanie / Windisch, Manfred / Hümpel, Michael / Rossberg, Wolfgang / Wolzt, Michael / Willbold, Dieter (Corresponding author)
Contributing Institute:	Strukturbiochemie; IBI-7 Physik der Medizinischen Bildgebung; INM-4
Published in:	Alzheimer's & dementia / Translational research & clinical interventions Translational research & clinical interventions [...], 6 (2020) 1, S. e12001
Imprint:	Amsterdam [u.a.] Elsevier 2020
DOI:	10.1002/trc2.12001
PubMed ID:	32211506
Document Type:	Journal Article
Research Program:	Physical Basis of Diseases
Link:	Get full text OpenAccess Get full text OpenAccess OpenAccess OpenAccess
	Publikationsportal JuSER

Please use the identifier: http://hdl.handle.net/2128/25100 in citations.
Please use the identifier: http://dx.doi.org/10.1002/trc2.12001 in citations.

IntroductionPRI‐002 is an orally available anti–amyloid beta (Aβ) prionic compound developed for direct disassembly of toxic Aβ oligomers relevant to Alzheimer's disease.MethodsTwo 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.ResultsPRI‐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.ConclusionsThe safety and PK results encourage further clinical development of PRI‐002.