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 |