A randomized, placebo-controlled, double-blind, dose escalation, single dose, and steady-state pharmacokinetic study of 9cuab30 in healthy volunteers

Jill M. Kolesar, Shannon Andrews, Heather Green, Tom C. Havighurst, Barbara W. Wollmer, Katina DeShong, Douglas E. Laux, Helen Krontiras, Donald D. Muccio, Kyung Mann Kim, Clinton J. Grubbs, Margaret G. House, Howard L. Parnes, Brandy M. Heckman-Stoddard, Howard H. Bailey

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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 (n = 8) or placebo (n = 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 20mg 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.

Original languageEnglish
Pages (from-to)903-912
Number of pages10
JournalCancer Prevention Research
Issue number12
StatePublished - 2019

Bibliographical note

Funding Information:
The authors would like to thank the University of Wisconsin Carbone Cancer Center (UWCCC) for use of its facilities to complete this research. The authors would like to thank the study participants for making this research possible. This research was supported by a contract from the NCI's Division of Cancer Prevention, a component of the NIH in the U.S. Department of Health and Human Services. Supported by the NCI, N01-CN-35153 and N01-CN-05014-69 (Phase I and II Clinical Trials of Chemoprevention Agent) and the UL1 TR000427 grant from National Center for Advancing Translational Sciences, National Institutes of Health. This work was also supported in part by NIH/NCI P30 CA014520-UW Comprehensive Cancer Center Support Grant.

Publisher Copyright:
© 2019 American Association for Cancer Research.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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