PMID- 26499175
OWN - NLM
STAT- MEDLINE
DCOM- 20161214
LR  - 20171116
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 174
IP  - 2
DP  - 2016 Feb
TI  - A randomized, phase IIa exploratory trial to assess the safety and preliminary 
      efficacy of LEO 43204 in patients with actinic keratosis.
PG  - 305-11
LID - 10.1111/bjd.14245 [doi]
AB  - BACKGROUND: LEO 43204 is a novel ingenol derivative in development for the 
      treatment of actinic keratosis. OBJECTIVES: To compare the safety and preliminary 
      efficacy of three doses of LEO 43204 with ingenol mebutate in actinic keratoses 
      (AKs). METHODS: Patients with at least three visible, discrete, nonkeratotic AKs 
      on four separate selected treatment areas on the forearms received LEO 43204 gel 
      (0.025%, 0.05% and 0.075%) and ingenol mebutate 0.05% gel, by 
      investigator-blinded, randomized allocation, for 2 consecutive days. Patients 
      were assessed at 8 weeks. Primary outcomes included maximum composite local skin 
      response (LSR) score and adverse events (AEs). Secondary outcomes included a 
      reduction in the number of visible AKs. RESULTS: Forty patients completed the 
      trial. For all treatments, mean LSR scores peaked at week 1, and were below 
      baseline by week 8. Mean maximum composite LSR scores for LEO 43204 0.025%, 0.05% 
      and 0.075% were 9.2 (Dunnett adjusted P = 0.02), 10.1 (Dunnett adjusted P = 0.90) 
      and 11.2 (Dunnett adjusted P < 0.01), respectively, vs. ingenol mebutate 0.05% 
      gel (10.0). The most frequent AEs across all treatments were application site 
      pruritus, burning sensation and tenderness. Mean reduction in the number of AKs 
      was comparable for ingenol mebutate and the two lowest doses of LEO 43204 
      (71.9-73.1%), but LEO 43204 0.075% gave a significantly larger reduction (81.8%; 
      Dunnett adjusted P = 0.04). CONCLUSIONS: LEO 43204 had a similar safety profile 
      to ingenol mebutate and a dose-response relationship for LSRs was demonstrated. 
      The highest LEO 43204 dose (0.075%) significantly reduced the AK count when 
      compared with ingenol mebutate.
CI  - (c) 2015 The Authors. British Journal of Dermatology published by John Wiley & Sons 
      Ltd on behalf of British Association of Dermatologists.
FAU - Sinnya, S
AU  - Sinnya S
AD  - Dermatology Research Centre, The University of Queensland, School of Medicine, 
      Translational Research Institute, Brisbane, QLD, Australia.
AD  - Dermatology Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.
FAU - Tan, J M
AU  - Tan JM
AD  - Dermatology Research Centre, The University of Queensland, School of Medicine, 
      Translational Research Institute, Brisbane, QLD, Australia.
AD  - Dermatology Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.
FAU - Prow, T W
AU  - Prow TW
AD  - Dermatology Research Centre, The University of Queensland, School of Medicine, 
      Translational Research Institute, Brisbane, QLD, Australia.
FAU - Primiero, C
AU  - Primiero C
AD  - Dermatology Research Centre, The University of Queensland, School of Medicine, 
      Translational Research Institute, Brisbane, QLD, Australia.
FAU - McEniery, E
AU  - McEniery E
AD  - Dermatology Research Centre, The University of Queensland, School of Medicine, 
      Translational Research Institute, Brisbane, QLD, Australia.
FAU - Selmer, J
AU  - Selmer J
AD  - LEO Pharma A/S, Ballerup, Denmark.
FAU - Osterdal, M L
AU  - Osterdal ML
AD  - LEO Pharma A/S, Ballerup, Denmark.
FAU - Soyer, H P
AU  - Soyer HP
AD  - Dermatology Research Centre, The University of Queensland, School of Medicine, 
      Translational Research Institute, Brisbane, QLD, Australia.
AD  - Dermatology Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160109
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Dermatologic Agents)
RN  - 0 (Diterpenes)
RN  - 0 (LEO 43204)
RN  - IC77UZI9G8 (ingenol)
SB  - IM
CIN - Br J Dermatol. 2016 Feb;174(2):260-1. PMID: 26871916
MH  - Administration, Cutaneous
MH  - Aged
MH  - Aged, 80 and over
MH  - Dermatologic Agents/*administration & dosage/adverse effects
MH  - Diterpenes/administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Keratosis, Actinic/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
EDAT- 2015/10/27 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/10/27 06:00
PHST- 2015/10/19 00:00 [accepted]
PHST- 2015/10/27 06:00 [entrez]
PHST- 2015/10/27 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1111/bjd.14245 [doi]
PST - ppublish
SO  - Br J Dermatol. 2016 Feb;174(2):305-11. doi: 10.1111/bjd.14245. Epub 2016 Jan 9.