PMID- 19220279
OWN - NLM
STAT- MEDLINE
DCOM- 20091214
LR  - 20211020
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 67
IP  - 3
DP  - 2009 Mar
TI  - Reduction of dietary fat absorption by the novel gastrointestinal lipase 
      inhibitor cetilistat in healthy volunteers.
PG  - 309-15
LID - 10.1111/j.1365-2125.2008.03311.x [doi]
AB  - AIMS: To assess the efficacy, pharmacodynamics, safety and tolerability of a 
      range of doses of cetilistat, a novel inhibitor of gastrointestinal lipases, in 
      healthy volunteers. METHODS: Three Phase I, randomized, placebo-controlled, 
      parallel-group studies were conducted. Enrolled subjects in the three studies (n 
      = 99) received a controlled calorie diet (total intake 2160 calories daily, 30% 
      from fat). Twenty-four subjects were randomized to placebo and 66 were randomized 
      to the following cetilistat doses: 50 mg three times daily [t.i.d. (n = 7)], 60 
      mg t.i.d. (n = 9), 100 mg t.i.d. (n = 7), 120 mg t.i.d. (n = 9), 150 mg t.i.d. (n 
      = 16), 240 mg t.i.d. (n = 9) and 300 mg t.i.d. (n = 9). Nine subjects received 
      the approved orlistat dose (120 mg t.i.d.). Treatment was for 5 days, with a 
      2-day run-in period and 1-day post-treatment follow-up. The primary outcome 
      measure was daily faecal fat excretion. Secondary outcomes included plasma lipid 
      levels, tolerability [gastrointestinal adverse events (AEs)] and safety. RESULTS: 
      Cetilistat increased faecal fat excretion relative to baseline at all doses. 
      Cetilistat was well tolerated, with gastrointestinal AEs the most common (51%). 
      Steatorrhoea (oily stool) was more frequent in the orlistat group (4.11 events 
      per subject) than in any cetilistat dose group (0.14-1.81 events per subject). 
      Most AEs (98%) were mild or moderate in intensity. CONCLUSIONS: Cetilistat 
      increased dietary fat excretion in healthy volunteers receiving a controlled 
      calorie diet. Cetilistat was well tolerated at all doses examined and 
      tolerability appeared to be improved relative to orlistat. Faecal fat excretion 
      in the cetilistat groups was at least comparable to the orlistat 120 mg t.i.d. 
      group.
FAU - Bryson, Andrew
AU  - Bryson A
AD  - Alizyme Therapeutics Ltd, Great Abington, Cambridge, UK. 
      andrew.bryson@alizyme.com
FAU - de la Motte, Stephan
AU  - de la Motte S
FAU - Dunk, Christopher
AU  - Dunk C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20080919
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Anti-Obesity Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Dietary Fats)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lactones)
RN  - 95M8R751W8 (Orlistat)
RN  - EC 3.1.1.3 (Lipase)
RN  - LC5G1JUA39 (cetilistat)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anti-Obesity Agents/administration & dosage/adverse effects/*pharmacology
MH  - Benzoxazines/administration & dosage/adverse effects/*pharmacology
MH  - Dietary Fats/antagonists & inhibitors/*pharmacokinetics
MH  - Double-Blind Method
MH  - Enzyme Inhibitors/administration & dosage/adverse effects/*pharmacology
MH  - Humans
MH  - Intestinal Absorption/*drug effects
MH  - Lactones/administration & dosage/adverse effects/pharmacology
MH  - Lipase/*antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - Obesity/drug therapy
MH  - Orlistat
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC2675041
EDAT- 2009/02/18 09:00
MHDA- 2009/12/16 06:00
PMCR- 2010/03/01
CRDT- 2009/02/18 09:00
PHST- 2009/02/18 09:00 [entrez]
PHST- 2009/02/18 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - BCP3311 [pii]
AID - 10.1111/j.1365-2125.2008.03311.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2009 Mar;67(3):309-15. doi: 
      10.1111/j.1365-2125.2008.03311.x. Epub 2008 Sep 19.