PMID- 30822774
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20210109
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 44
IP  - 11
DP  - 2019 Oct
TI  - Randomized, double-blind, placebo-controlled study of F17464, a preferential D(3) 
      antagonist, in the treatment of acute exacerbation of schizophrenia.
PG  - 1917-1924
LID - 10.1038/s41386-019-0355-2 [doi]
AB  - F17464, a highly potent preferential D3 antagonist, is a novel compound in 
      development for schizophrenia treatment. This phase II, double-blind, randomized, 
      placebo-controlled, parallel-group study in five European countries evaluated the 
      efficacy and safety of F17464, 20 mg twice daily, versus placebo over 6 weeks in 
      patients with acute exacerbation of schizophrenia. Change from baseline to Day 43 
      of the Positive and Negative Syndrome Scale (PANSS) total score was the primary 
      outcome. The data from 134 randomized patients (67 per group) were analyzed 
      (efficacy/safety). Using analysis of covariance (ANCOVA) after last observation 
      carried forward (LOCF) imputation (primary analysis), the PANSS total score 
      reduction was statistically significantly greater for F17464 than placebo treated 
      subjects at endpoint (p = 0.014); using ANCOVA with Multiple Imputation (MI) 
      method, the between-group difference was in favor of F17464 but did not reach 
      statistical significance. Differences in PANSS positive and general 
      psychopathology subscale score, Marder positive factor score, PANSS response, and 
      PANSS resolution criteria were also statistically significant in favor of F17464 
      (p values < 0.05) using the LOCF method, with similar results as for the primary 
      analysis using the MI method. Treatment-related adverse events (AEs) were 
      reported in 49.3% and 46.3% of patients on F17464 and placebo, respectively. The 
      most common AEs in F17464 group: insomnia, agitation, and increased 
      triglycerides; worsening of schizophrenia/drug ineffective was less frequent in 
      F17464. Interestingly, no weight gain, no extrapyramidal disorder except rare 
      akathisia were observed under F17464. This 6-week trial demonstrated therapeutic 
      efficacy of 40 mg/day F17464 in improving symptoms of acute exacerbation of 
      schizophrenia with a favorable safety profile.
FAU - Bitter, Istvan
AU  - Bitter I
AD  - Department of Psychiatry and Psychotherapy, Semmelweis University, Balassa u.6, 
      Budapest, 1083, Hungary.
FAU - Lieberman, Jeffrey A
AU  - Lieberman JA
AD  - New York Presbyterian Hospital - Columbia University Medical Center, 1051 
      Riverside Drive, New York, NY, 10032, USA.
FAU - Gaudoux, Florence
AU  - Gaudoux F
AD  - Institut de Recherche Pierre Fabre, 3 avenue Hubert Curien, Toulouse, 31000, 
      France.
FAU - Sokoloff, Pierre
AU  - Sokoloff P
AD  - PSAdvice, Impasse Larosa, Ile-aux-Moines, 56780, France.
FAU - Groc, Melanie
AU  - Groc M
AD  - Institut de Recherche Pierre Fabre, 3 avenue Hubert Curien, Toulouse, 31000, 
      France.
FAU - Chavda, Rajeev
AU  - Chavda R
AD  - Galderma, Rue D'Entre-deux-Villes 10, La Tour de Peilz, 1814, Switzerland.
FAU - Delsol, Cecile
AU  - Delsol C
AD  - Institut de Recherche Pierre Fabre, 3 avenue Hubert Curien, Toulouse, 31000, 
      France.
FAU - Barthe, Laurence
AU  - Barthe L
AD  - Institut de Recherche Pierre Fabre, 3 avenue Hubert Curien, Toulouse, 31000, 
      France.
FAU - Brunner, Valerie
AU  - Brunner V
AD  - IRIS Servier, 50 rue Carot, Suresnes Cedex, 92284, France.
FAU - Fabre, Carine
AU  - Fabre C
AD  - Institut de Recherche Pierre Fabre, 3 avenue Hubert Curien, Toulouse, 31000, 
      France.
FAU - Fagard, Marine
AU  - Fagard M
AD  - Institut de Recherche Pierre Fabre, 3 avenue Hubert Curien, Toulouse, 31000, 
      France.
FAU - Montagne, Agnes
AU  - Montagne A
AD  - Institut de Recherche Pierre Fabre, 3 avenue Hubert Curien, Toulouse, 31000, 
      France.
FAU - Tonner, Francoise
AU  - Tonner F
AUID- ORCID: 0000-0002-0327-2170
AD  - Institut de Recherche Pierre Fabre, 3 avenue Hubert Curien, Toulouse, 31000, 
      France. francoise.tonner@pierre-fabre.com.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190301
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Receptors, Dopamine D3)
SB  - IM
MH  - Adult
MH  - Akathisia, Drug-Induced
MH  - Antipsychotic Agents/adverse effects/*therapeutic use
MH  - Dopamine Antagonists/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Receptors, Dopamine D3/*antagonists & inhibitors
MH  - Schizophrenia/*drug therapy
MH  - Sleep Initiation and Maintenance Disorders/chemically induced
MH  - Treatment Outcome
PMC - PMC6785149
EDAT- 2019/03/02 06:00
MHDA- 2020/07/07 06:00
PMCR- 2020/10/01
CRDT- 2019/03/02 06:00
PHST- 2018/09/04 00:00 [received]
PHST- 2019/02/21 00:00 [accepted]
PHST- 2019/02/20 00:00 [revised]
PHST- 2019/03/02 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2019/03/02 06:00 [entrez]
PHST- 2020/10/01 00:00 [pmc-release]
AID - 10.1038/s41386-019-0355-2 [pii]
AID - 355 [pii]
AID - 10.1038/s41386-019-0355-2 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2019 Oct;44(11):1917-1924. doi: 
      10.1038/s41386-019-0355-2. Epub 2019 Mar 1.