Journal article
A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers
Cancer prevention research (Philadelphia, Pa.), Vol.12(12), pp.903-912
12/2019
DOI: 10.1158/1940-6207.CAPR-19-0310
PMCID: PMC7008944
PMID: 31484659
Abstract
9cUAB30 is a synthetic analogue of 9-cis retinoic acid with chemoprevention activity in cell lines and animal models. The purpose of this phase I placebo-controlled, double-blinded, dose escalation study of 9cUAB30 was to evaluate its safety, pharmacokinetics, and determine a dose for future phase II studies. Participants received a single dose of study drug (placebo or 9cUAB30) on day 1 followed by a 6-day drug-free period and then 28 days of continuous daily dosing starting on day 8. Fifty-three healthy volunteers were enrolled into five dose cohorts (20, 40, 80, 160, and 240 mg). Participants were randomized within each dose level to receive either 9cUAB30 (
= 8) or placebo (
= 2). 9cUAB30 was well tolerated, with no dose limiting toxicities reported and no evidence of persistent elevations in serum triglycerides or cholesterol. Treatment-emergent grade 3 hypertension occurred in 1 of 8 participants at the 20 mg dose level and in 2 of 8 at the 240 mg dose level, all considered unlikely related to study agent; no other grade 3 adverse events were observed. The AUC increased, as expected, between day 1 (single dose) and day 36 (steady state). Pharmacokinetics were linear in dose escalation through 160 mg. 9cUAB30 administered by daily oral dosing has a favorable safety and pharmacokinetic profile. On the basis of the observed safety profile and lack of linearity in pharmacokinetics at doses greater than 160 mg, the recommended phase II dose with the current formulation is 160 mg once daily.
Details
- Title: Subtitle
- A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers
- Creators
- Jill M Kolesar - University of KentuckyShannon Andrews - University of Wisconsin Carbone Cancer CenterHeather Green - University of Wisconsin Carbone Cancer CenterTom C Havighurst - University of Wisconsin–MadisonBarbara W Wollmer - University of Wisconsin Carbone Cancer CenterKatina DeShong - University of Wisconsin Carbone Cancer CenterDouglas E Laux - University of IowaHelen Krontiras - University of Alabama at BirminghamDonald D Muccio - University of Alabama at BirminghamKyungMann Kim - University of Wisconsin Carbone Cancer CenterClinton J Grubbs - University of Alabama at BirminghamMargaret G House - National Cancer InstituteHoward L Parnes - National Cancer InstituteBrandy M Heckman-Stoddard - National Cancer InstituteHoward H Bailey - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cancer prevention research (Philadelphia, Pa.), Vol.12(12), pp.903-912
- DOI
- 10.1158/1940-6207.CAPR-19-0310
- PMID
- 31484659
- PMCID
- PMC7008944
- ISSN
- 1940-6207
- eISSN
- 1940-6215
- Grant note
- UL1 TR000427 / NCATS NIH HHS P30 DK079626 / NIDDK NIH HHS N01CN35153 / NCI NIH HHS P30 CA014520 / NCI NIH HHS UL1 TR002373 / NCATS NIH HHS
- Language
- English
- Date published
- 12/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984359917002771
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