PMID- 29204958
OWN - NLM
STAT- MEDLINE
DCOM- 20180724
LR  - 20210223
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 38
IP  - 3
DP  - 2018 Mar
TI  - Pharmacokinetics and Safety of Ingenol Disoxate Gel Administered Under 
      Maximum-Use Conditions to Patients With Actinic Keratosis.
PG  - 249-257
LID - 10.1007/s40261-017-0608-y [doi]
AB  - BACKGROUND AND OBJECTIVES: Ingenol disoxate (LEO 43204) is a field therapy in 
      development for the treatment of actinic keratosis (AK) on areas between 25 and 
      250 cm(2). We evaluated the systemic exposure and safety of ingenol disoxate 
      under maximum-use conditions. METHODS: This was a phase I, open-label, 
      non-randomized, multicenter trial. Patients >/= 18 years of age with >/= 15 
      clinically typical, visible, discrete AK lesions in a treatment area on the full 
      face or approximately 250 cm(2) on the arm or scalp were treated once-daily for 3 
      consecutive days with ingenol disoxate 0.018, 0.1, or 0.037% gel, respectively. 
      RESULTS: The trial included 58 patients. Median age (range) of patients was 68 
      years (42-89) [face, N = 18], 66 years (43-88) [arm, N = 21], and 67 years 
      (37-83) [scalp, N = 19]. The highest quantifiable ingenol disoxate level was 
      observed in the arm group (0.33 nM, area under the concentration-time curve from 
      time zero to the last data point [AUC(tlast)] 3.12 nM.h). Mean composite local 
      skin response scores peaked at Day 4 and declined towards baseline by Day 15 in 
      all treatment groups. Most adverse events (AEs) were of mild or moderate 
      intensity; the most common treatment-related AEs were application-site pain 
      (face, 88.9%; arm, 57.1%; scalp, 100.0%) and application-site pruritus (face, 
      50.0%; arm, 52.4%; scalp, 42.1%). CONCLUSION: Very low systemic exposure to 
      ingenol disoxate was observed when applied to the face, arm, or scalp in patients 
      with AK under maximum-use conditions. No new safety signals were identified. 
      TRIAL REGISTRATION: NCT02424305.
FAU - Lain, Edward
AU  - Lain E
AUID- ORCID: 0000-0002-0762-1251
AD  - Austin Institute for Clinical Research, 302 N Heatherwilde Boulevard #200, 
      Pflugerville, TX, 78660, USA. ted.lain@atxderm.com.
FAU - Skov, Torsten
AU  - Skov T
AD  - LEO Pharma A/S, Ballerup, Denmark.
FAU - Hall, Anders
AU  - Hall A
AD  - LEO Pharma A/S, Ballerup, Denmark.
LA  - eng
SI  - ClinicalTrials.gov/NCT02424305
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Diterpenes)
RN  - 0 (Gels)
RN  - 0 (LEO 43204)
RN  - IC77UZI9G8 (ingenol)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Diterpenes/administration & dosage/*adverse effects/*blood/pharmacokinetics
MH  - Female
MH  - Gels
MH  - Humans
MH  - Keratosis, Actinic/*blood/diagnosis/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Pain/blood/chemically induced
MH  - Pruritus/blood/chemically induced
MH  - Treatment Outcome
EDAT- 2017/12/06 06:00
MHDA- 2018/07/25 06:00
CRDT- 2017/12/06 06:00
PHST- 2017/12/06 06:00 [pubmed]
PHST- 2018/07/25 06:00 [medline]
PHST- 2017/12/06 06:00 [entrez]
AID - 10.1007/s40261-017-0608-y [pii]
AID - 10.1007/s40261-017-0608-y [doi]
PST - ppublish
SO  - Clin Drug Investig. 2018 Mar;38(3):249-257. doi: 10.1007/s40261-017-0608-y.