PMID- 29177699
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240330
IS  - 2193-8253 (Print)
IS  - 2193-6536 (Electronic)
IS  - 2193-6536 (Linking)
VI  - 7
IP  - 1
DP  - 2018 Jun
TI  - A Phase IC Study Evaluating the Safety, Tolerability, Pharmacokinetics, and 
      Cognitive Outcomes of BI 409306 in Patients with Mild-to-Moderate Schizophrenia.
PG  - 129-139
LID - 10.1007/s40120-017-0085-5 [doi]
AB  - INTRODUCTION: This randomized, double-blind, parallel-group study investigated 
      the safety, tolerability, pharmacokinetics (PK), and cognitive outcomes of BI 
      409306-a selective phosphodiesterase 9A (PDE9A) inhibitor-in patients with 
      schizophrenia. METHODS: Patients with mild-to-moderate schizophrenia were 
      randomized (1:1:1:1) to receive BI 409306 at 25, 50, or 100 mg or placebo once 
      daily over 14 days. The primary endpoints were safety and tolerability; the 
      secondary endpoints were PK and cognitive outcomes. RESULTS: Of the 40 randomized 
      patients, 38 (95%) completed the study. Patients were predominantly male (87.5%; 
      mean age, 40.2 years). After a single dose, C (max) was reached within 30-45 min. 
      The geometric mean (gMean) C (max) and AUC(0-infinity) ranged from 138 to 998 nmol/L and 
      217 to 2020 nmol∙h/L, respectively. Elimination was rapid (gMean t (1/2) range 
      1.10-1.85 h). After multiple doses, C (max,ss) was reached within 1 h; 
      elimination was similar to that observed after a single dose. Total exposure at 
      steady state and after a single dose were similar (accumulation ratio range: AUC, 
      0.758-1.13 and C(max), 0.768-1.40). No deaths, adverse events (AEs) leading to 
      discontinuation, or serious AEs were observed. Treatment-emergent AEs were mild, 
      with no apparent dose-related trends. There was no worsening of schizophrenia 
      symptoms (Positive and Negative Syndrome Scale) and no trends in suicidality 
      (Columbia Suicide Severity Rating Scale). The Hopkins Verbal Learning 
      Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) showed 
      no effect on cognitive function. CONCLUSION: Administration of BI 409306 in 
      patients with mild-to-moderate schizophrenia resulted in satisfactory safety and 
      tolerability. BI 409306, PK was characterized by rapid absorption, monophasic to 
      biphasic elimination, and minor accumulation with multiple dosing. TRIAL 
      REGISTRATION: ClinicalTrials.gov identifier NCT01892384. FUNDING: Boehringer 
      Ingelheim Pharma GmbH & Co. KG.
FAU - Brown, David
AU  - Brown D
AD  - Community Clinical Research, Inc., Austin, TX, USA.
FAU - Daniels, Kristen
AU  - Daniels K
AD  - Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
FAU - Pichereau, Solen
AU  - Pichereau S
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Sand, Michael
AU  - Sand M
AD  - Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. 
      michael.sand@boehringer-ingelheim.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01892384
PT  - Journal Article
DEP - 20171124
PL  - New Zealand
TA  - Neurol Ther
JT  - Neurology and therapy
JID - 101637818
PMC - PMC5990500
OTO - NOTNLM
OT  - BI 409306
OT  - Cognitive outcome
OT  - PDE9A
OT  - Pharmacokinetics
OT  - Phase I
OT  - Phosphodiesterase inhibitor
OT  - Safety
OT  - Schizophrenia
OT  - Tolerability
EDAT- 2017/11/28 06:00
MHDA- 2017/11/28 06:01
PMCR- 2017/11/24
CRDT- 2017/11/28 06:00
PHST- 2017/08/24 00:00 [received]
PHST- 2017/11/28 06:00 [pubmed]
PHST- 2017/11/28 06:01 [medline]
PHST- 2017/11/28 06:00 [entrez]
PHST- 2017/11/24 00:00 [pmc-release]
AID - 10.1007/s40120-017-0085-5 [pii]
AID - 85 [pii]
AID - 10.1007/s40120-017-0085-5 [doi]
PST - ppublish
SO  - Neurol Ther. 2018 Jun;7(1):129-139. doi: 10.1007/s40120-017-0085-5. Epub 2017 Nov 
      24.