PMID- 32935460
OWN - NLM
STAT- MEDLINE
DCOM- 20220324
LR  - 20220324
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Print)
IS  - 2160-763X (Linking)
VI  - 10
IP  - 4
DP  - 2021 Apr
TI  - A Randomized, Double-Blind, Placebo- and Positive-Controlled, 4-Period Crossover 
      Study of the Effects of Solriamfetol on QTcF Intervals in Healthy Participants.
PG  - 404-413
LID - 10.1002/cpdd.867 [doi]
AB  - Solriamfetol, a dopamine and norepinephrine reuptake inhibitor, is approved 
      (United States and European Union; Sunosi) to treat excessive daytime sleepiness 
      associated with narcolepsy (75-150 mg/day) or obstructive sleep apnea 
      (37.5-150 mg/day). A thorough QT/QTc study assessed solriamfetol effects on QT 
      interval (Fridericia correction for heart rate; QTcF). This randomized, 
      double-blind, placebo- and positive-controlled, 4-period crossover study compared 
      single doses of 300 and 900 mg solriamfetol, 400 mg moxifloxacin, and placebo in 
      healthy adults. Placebo- and predose-adjusted mean differences in QTcF (ddQTcF; 
      primary end point) were analyzed, and solriamfetol pharmacokinetics were 
      characterized. Fifty-five participants completed all periods. Upper bounds of 
      2-sided 90% confidence intervals (CIs) for ddQTcF for both solriamfetol doses 
      were <10 milliseconds at all postdose time points. Assay sensitivity was 
      demonstrated with moxifloxacin; lower bounds of 2-sided 90%CIs for ddQTcF > 5 
      milliseconds at 1, 2, and 3 hours postdose. There were no QTcF increases > 60 
      milliseconds or QTcF values > 480 milliseconds at either solriamfetol dose. 
      Solriamfetol median t(max) was 2-3 hours; exposure was dose-proportional. More 
      participants experienced adverse events (AEs) after solriamfetol 900 versus 
      300 mg (70% vs 29%); none were serious (all mild/moderate), and there were no 
      deaths. Common AEs were nausea, dizziness, and palpitations. Neither solriamfetol 
      dose resulted in QTcF prolongation > 10 milliseconds.
CI  - (c) 2020 The Authors. Clinical Pharmacology in Drug Development published by Wiley 
      Periodicals LLC on behalf of American College of Clinical Pharmacology.
FAU - Zomorodi, Katie
AU  - Zomorodi K
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
FAU - Chen, Dan
AU  - Chen D
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
FAU - Lee, Lawrence
AU  - Lee L
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
FAU - Swearingen, Dennis
AU  - Swearingen D
AD  - Celerion, Tempe, Arizona, USA.
FAU - Carter, Lawrence P
AU  - Carter LP
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200915
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Carbamates)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - 939U7C91AI (solriamfetol)
RN  - U188XYD42P (Moxifloxacin)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Adult
MH  - Carbamates/administration & dosage/*adverse effects/pharmacokinetics
MH  - Cross-Over Studies
MH  - Dopamine Uptake Inhibitors/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - *Electrocardiography
MH  - Female
MH  - Humans
MH  - Long QT Syndrome/*chemically induced
MH  - Male
MH  - Middle Aged
MH  - Moxifloxacin/adverse effects
MH  - Phenylalanine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Young Adult
PMC - PMC8048583
OTO - NOTNLM
OT  - ECG
OT  - JZP-110
OT  - QTc
OT  - Sunosi
OT  - pharmacokinetics
OT  - safety
OT  - solriamfetol
COIS- K. Zomorodi, D. Chen, and L. Carter are employees of Jazz Pharmaceuticals, who in 
      the course of their employment, have received stock options exercisable for, and 
      other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. L . Lee is a 
      former employee of Jazz Pharmaceuticals, who in the course of his employment, has 
      received stock options exercisable for, and other stock awards of, ordinary 
      shares of Jazz Pharmaceuticals plc. D. Swearingen has nothing to disclose.
EDAT- 2020/09/17 06:00
MHDA- 2022/03/25 06:00
PMCR- 2021/04/15
CRDT- 2020/09/16 05:44
PHST- 2020/05/06 00:00 [received]
PHST- 2020/08/17 00:00 [accepted]
PHST- 2020/09/17 06:00 [pubmed]
PHST- 2022/03/25 06:00 [medline]
PHST- 2020/09/16 05:44 [entrez]
PHST- 2021/04/15 00:00 [pmc-release]
AID - CPDD867 [pii]
AID - 10.1002/cpdd.867 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2021 Apr;10(4):404-413. doi: 10.1002/cpdd.867. Epub 2020 
      Sep 15.