AZD3293: Pharmacokinetic and Pharmacodynamic Effects in Healthy Subjects and Patients with Alzheimer's Disease. (Record no. 3160)

MARC details
000 -LEADER
fixed length control field 03804nam a22006737a 4500
008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION
fixed length control field 180309s20172017 xxu||||| |||| 00| 0 eng d
022 ## - INTERNATIONAL STANDARD SERIAL NUMBER
International Standard Serial Number 1387-2877
024 ## - OTHER STANDARD IDENTIFIER
Standard number or code 10.3233/JAD-160701 [doi]
024 ## - OTHER STANDARD IDENTIFIER
Standard number or code JAD160701 [pii]
040 ## - CATALOGING SOURCE
Original cataloging agency Ovid MEDLINE(R)
099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC)
PMID 27767991
245 ## - TITLE STATEMENT
Title AZD3293: Pharmacokinetic and Pharmacodynamic Effects in Healthy Subjects and Patients with Alzheimer's Disease.
251 ## - Source
Source Journal of Alzheimer's Disease. 55(3):1039-1053, 2017
252 ## - Abbreviated Source
Abbreviated source J Alzheimers Dis. 55(3):1039-1053, 2017
253 ## - Journal Name
Journal name Journal of Alzheimer's disease : JAD
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Year 2017
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Manufacturer FY2017
266 ## - Date added to catalog
Date added to catalog 2018-04-19
520 ## - SUMMARY, ETC.
Abstract AZD3293 (LY3314814) is a promising new potentially disease-modifying BACE1 (beta-secretase) inhibitor in Phase III clinical development for the treatment of Alzheimer's disease. Reported here are the first two Phase I studies: (1) a single ascending dose study evaluating doses of 1-750 mg with a food-effect component (n = 72), and (2) a 2-week multiple ascending dose study evaluating doses of 15 or 50 mg once daily (QD) or 70 mg once weekly (QW) in elderly subjects (Part 1, n = 31), and 15, 50, or 150 mg QD in patients with mild to moderate Alzheimer's disease (Part 2, n = 16). AZD3293 was generally well tolerated up to the highest doses given. No notable food effects were observed. PK following multiple doses (Part 2) were tmax of 1 to 3 h and mean t1/2 of 16 to 21 h across the 15 to 150 mg dose range. For single doses of >=5 mg, a >=70% reduction was observed in mean plasma Abeta40 and Abeta42 concentrations, with prolonged suppression for up to 3 weeks at the highest dose level studied. Following multiple doses, robust reductions in plasma (>=64% at 15 mg and >=78% at >=50 mg) and cerebrospinal fluid (>=51% at 15 mg and >=76% at >=50 mg) Abeta peptides were seen, including prolonged suppression even with a QW dosing regimen. AZD3293 is the only BACE1 inhibitor for which prolonged suppression of plasma Abeta with a QW dosing schedule has been reported. Two Phase III studies of AZD3293 (AMARANTH, NCT02245737; and DAYBREAK-ALZ, NCT02783573) are now ongoing.
546 ## - LANGUAGE NOTE
Language note English
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Alzheimer Disease/dt [Drug Therapy]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Antipsychotic Agents/pk [Pharmacokinetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Antipsychotic Agents/tu [Therapeutic Use]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Imidazoles/pk [Pharmacokinetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Imidazoles/tu [Therapeutic Use]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Spiro Compounds/pk [Pharmacokinetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Spiro Compounds/tu [Therapeutic Use]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Adolescent
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Adult
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Age Factors
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Aged
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Aged, 80 and over
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Amyloid beta-Peptides/bl [Blood]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Amyloid beta-Peptides/cf [Cerebrospinal Fluid]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Cross-Over Studies
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Dose-Response Relationship, Drug
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Double-Blind Method
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Drug Administration Schedule
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Female
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Follow-Up Studies
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Food
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Healthy Volunteers
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Humans
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Male
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Middle Aged
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Neurologic Examination
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Peptide Fragments/bl [Blood]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Peptide Fragments/cf [Cerebrospinal Fluid]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Time Factors
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Young Adult
651 ## - SUBJECT ADDED ENTRY--GEOGRAPHIC NAME
Institution MedStar Harbor Hospital
657 ## - INDEX TERM--FUNCTION
Medline publication type Clinical Trial, Phase I
657 ## - INDEX TERM--FUNCTION
Medline publication type Journal Article
657 ## - INDEX TERM--FUNCTION
Medline publication type Randomized Controlled Trial
700 ## - ADDED ENTRY--PERSONAL NAME
Local Authors Goldwater, Ronald
790 ## - Authors
All authors Alexander RC, Cebers G, Eketjall S, Ereshefsky L, Goldwater R, Haeberlein SB, Han D, Kugler AR, Maltby J, Olsson T, Rosen L, Russell M, Ye N
856 ## - ELECTRONIC LOCATION AND ACCESS
DOI <a href="http://dx.doi.org/10.3233/JAD-160701">http://dx.doi.org/10.3233/JAD-160701</a>
Public note http://dx.doi.org/10.3233/JAD-160701
942 ## - ADDED ENTRY ELEMENTS (KOHA)
Koha item type Journal Article
Item type description Article
Holdings
Withdrawn status Lost status Damaged status Not for loan Collection Home library Current library Date acquired Total Checkouts Full call number Barcode Date last seen Price effective from Koha item type
          MedStar Authors Catalog MedStar Authors Catalog 04/19/2018   27767991 27767991 04/19/2018 04/19/2018 Journal Article

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