PMID- 26445139
OWN - NLM
STAT- Publisher
LR  - 20240228
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
DP  - 2015 Oct 7
TI  - A randomized, placebo-controlled repeat-dose thorough QT study of inhaled 
      loxapine in healthy volunteers.
AB  - OBJECTIVE: This randomized, double-blind, active- and placebo-controlled, 
      crossover, thorough QT study assessed the effect of two inhaled loxapine doses on 
      cardiac repolarization as measured by corrected QT (QTc) interval in healthy 
      subjects (ClinicalTrials.gov NCT01854710). METHODS: Subjects received two doses 
      of inhaled loxapine (10 mg) 2 hours apart + oral placebo, two doses of inhaled 
      placebo + oral placebo, or two doses of inhaled placebo + oral moxifloxacin (400 
      mg; positive control), with >/= 3 days washout between treatments. Two-sided 90% 
      confidence intervals (CIs) were calculated around least-squares mean predose 
      placebo-subtracted individually corrected QT durations (DeltaDeltaQTcIs) at 12 time 
      points throughout 24 hours after dosing. A DeltaDeltaQTcI 95% upper CI exceeding 10 msec 
      was the threshold indicating QTc prolongation (primary endpoint). Secondary 
      endpoints included Fridericia- and Bazettcorrected QT duration and QTcI outliers 
      Pharmacokinetics and adverse events (AEs) were also assessed. RESULTS: Of 60 
      subjects enrolled (mean age, 33.8 years; 52% male), 44 completed the study. Post 
      loxapine dosing, no DeltaDeltaQTcI 95% upper CI exceeded 10 msec; the largest was 6.31 
      msec 5 minutes post dose 2. Methodology was validated by DeltaDeltaQTcI 95% lower CIs 
      exceeding 5 msec at 9 of 12 time points after moxifloxacin dosing. Loxapine 
      plasma concentrations increased rapidly (mean Cmax, 177 ng/mL; median tmax 2 
      minutes after dose 2, 2.03 hours after dose 1). There were no deaths, serious 
      AEs, or AEs leading to discontinuation, and one severe AE. CONCLUSIONS: Primary 
      and secondary endpoints indicated two therapeutic doses of inhaled loxapine did 
      not cause threshold QTc prolongation in this study.
FAU - Cassella, James V
AU  - Cassella JV
FAU - Spyker, Daniel A
AU  - Spyker DA
FAU - Yeung, Paul P
AU  - Yeung PP
LA  - eng
SI  - ClinicalTrials.gov/NCT01854710
PT  - Journal Article
DEP - 20151007
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
EDAT- 2015/10/08 06:00
MHDA- 2015/10/08 06:00
CRDT- 2015/10/08 06:00
PHST- 2015/10/07 00:00 [accepted]
PHST- 2015/10/08 06:00 [entrez]
PHST- 2015/10/08 06:00 [pubmed]
PHST- 2015/10/08 06:00 [medline]
AID - 13795 [pii]
AID - 10.5414/CP202457 [doi]
PST - aheadofprint
SO  - Int J Clin Pharmacol Ther. 2015 Oct 7. doi: 10.5414/CP202457.