PMID- 30598342
OWN - NLM
STAT- MEDLINE
DCOM- 20200211
LR  - 20200211
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 41
IP  - 2
DP  - 2019 Feb
TI  - A Phase I, Randomized, Crossover, Open-label Study of the Pharmacokinetics of 
      Solriamfetol (JZP-110) in Healthy Adult Subjects With and Without Food.
PG  - 196-204
LID - S0149-2918(18)30600-3 [pii]
LID - 10.1016/j.clinthera.2018.12.001 [doi]
AB  - PURPOSE: Solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake 
      inhibitor with robust wake-promoting effects, is currently being evaluated for 
      the reduction of sleepiness and improvement of wakefulness in patients with 
      narcolepsy and obstructive sleep apnea. The purpose of this study was to evaluate 
      the effect of food on the pharmacokinetic (PK) parameters and bioavailability of 
      solriamfetol at the highest intended therapeutic dose in healthy adults and to 
      characterize its renal excretion under fasting conditions. METHODS: In this 
      open-label, randomized, crossover study, healthy adult subjects received a single 
      300-mg dose of solriamfetol in a fasted condition (10 h) and in a fed condition 
      (30 min after the start of a standardized high-fat, high-calorie breakfast), with 
      at least a 7-day washout period between doses. Blood samples for PK analyses were 
      collected during both conditions at prespecified time points. Urine samples were 
      collected up to 48 h postdose in the fasted condition. Samples were analyzed for 
      solriamfetol (plasma and urine) and N-acetyl solriamfetol (urine) by using 
      validated LC-MS/MS bioanalytical methods. The effect of food on solriamfetol 
      relative bioavailability was examined by comparing the 90% confidence intervals 
      (CIs) of the fed/fasted ratios of natural log-transformed PK parameters C(max), 
      AUC(0-t), and AUC(0-infinity) with the prespecified range of 80%-125%. Safety and 
      tolerability were also assessed. FINDINGS: A total of 32 subjects were enrolled 
      (50% female; 53.1% black, 46.9% white; mean age, 35.6 years), and 31 were 
      included in the PK analyses. Solriamfetol was rapidly absorbed in both 
      conditions. The 90% CIs for the fed/fasted geometric mean ratios were 89.2-98.8 
      for C(max) (ratio of 93.9%) and 93.8-101.5 for AUC(0-infinity) (ratio of 97.6%), 
      indicating the absence of a food effect. In the fasted condition, 89.8% of 
      solriamfetol was recovered in urine as unchanged drug over 48 h; 1.1% was 
      excreted as a minor metabolite, N-acetyl solriamfetol. A total of 55 adverse 
      events (AEs), all mild, were reported by 18 subjects (56.3%). The frequency and 
      type of AEs were similar in the 2 conditions; the most common AEs (insomnia, 
      headache, hypervigilance, decreased appetite, and nausea) were all mild in 
      severity and resolved without treatment. IMPLICATIONS: Solriamfetol relative 
      bioavailability was bioequivalent in the fed and fasted conditions, showing that 
      solriamfetol can be taken without regard to meals; furthermore, tolerability was 
      similar in both conditions. Renal excretion of unchanged drug is the primary 
      route of elimination.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Zomorodi, Katie
AU  - Zomorodi K
AD  - Jazz Pharmaceuticals, Palo Alto, CA, United States. Electronic address: 
      katie.zomorodi@jazzpharma.com.
FAU - Kankam, Martin
AU  - Kankam M
AD  - Vince and Associates Clinical Research, Overland Park, KS, United States.
FAU - Lu, Yuan
AU  - Lu Y
AD  - Jazz Pharmaceuticals, Palo Alto, CA, United States.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20181228
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Carbamates)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - 939U7C91AI (solriamfetol)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Biological Availability
MH  - Carbamates/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Fasting/*metabolism
MH  - Female
MH  - *Food-Drug Interactions
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phenylalanine/*analogs & derivatives/pharmacokinetics
MH  - Therapeutic Equivalency
OTO - NOTNLM
OT  - JZP-110
OT  - bioequivalence
OT  - food effects
OT  - pharmacokinetics
OT  - renal excretion
OT  - solriamfetol
EDAT- 2019/01/02 06:00
MHDA- 2020/02/12 06:00
CRDT- 2019/01/02 06:00
PHST- 2018/10/12 00:00 [received]
PHST- 2018/11/20 00:00 [revised]
PHST- 2018/12/03 00:00 [accepted]
PHST- 2019/01/02 06:00 [pubmed]
PHST- 2020/02/12 06:00 [medline]
PHST- 2019/01/02 06:00 [entrez]
AID - S0149-2918(18)30600-3 [pii]
AID - 10.1016/j.clinthera.2018.12.001 [doi]
PST - ppublish
SO  - Clin Ther. 2019 Feb;41(2):196-204. doi: 10.1016/j.clinthera.2018.12.001. Epub 
      2018 Dec 28.