PMID- 25310201
OWN - NLM
STAT- MEDLINE
DCOM- 20150728
LR  - 20151119
IS  - 1533-712X (Electronic)
IS  - 0271-0749 (Linking)
VI  - 34
IP  - 6
DP  - 2014 Dec
TI  - Safety and pharmacokinetics of lisdexamfetamine dimesylate in adults with 
      clinically stable schizophrenia: a randomized, double-blind, placebo-controlled 
      trial of ascending multiple doses.
PG  - 682-9
LID - 10.1097/JCP.0000000000000205 [doi]
AB  - To assess the safety and pharmacokinetics of lisdexamfetamine dimesylate (LDX), a 
      d-amphetamine prodrug, this double-blind study enrolled adults with clinically 
      stable schizophrenia who were adherent (>/=12 weeks) to antipsychotic 
      pharmacotherapy. The participants received placebo or ascending LDX doses (50, 
      70, 100, 150, 200, and 250 mg) daily for 5 days at each dose (dose periods, 1-6; 
      days, 1-5). Of the 31 enrolled participants, 27 completed the study (placebo, n = 
      6; LDX, n = 21). Treatment-emergent adverse events (AEs) were reported by 4 
      participants receiving placebo and by 23 participants receiving LDX (all doses) 
      with no serious AEs while on active treatment. For all periods, the mean postdose 
      change on day 5 (up to 12 hours postdose) in systolic and diastolic blood 
      pressure and pulse, respectively, ranged from -4.62 to 8.05 mm Hg, -3.67 to 4.43 
      mm Hg, and -3.57 to 14.43 beats per minute for placebo and -3.83 to 11.25 mm Hg, 
      -1.55 to 5.80 mm Hg, and -0.36 to 21.26 beats per minute for LDX. With ascending 
      LDX dose, the mean (SD) maximum plasma concentration for LDX-derived 
      d-amphetamine ranged from 51.68 (10.28) to 266.27 (56.55) ng/mL. The area under 
      the plasma concentration-time curve for 24 hours ranged from 801.8 (170.2) to 
      4397.9 (1085.9) ng[BULLET OPERATOR]h/mL. The d-amphetamine maximum plasma 
      concentration and area under the plasma concentration-time curve increased 
      linearly with ascending LDX dose. Antipsychotic agents did not markedly affect 
      d-amphetamine pharmacokinetics. Over a wide range of ascending doses, LDX safety 
      profile in adults with schizophrenia was consistent with previous findings with 
      no unexpected treatment-emergent AEs. Pulse tended to increase with LDX dose; 
      overall, blood pressure did not increase with LDX dose. Consistent with previous 
      studies, pharmacokinetic parameters increased linearly with increasing LDX dose.
FAU - Martin, Patrick
AU  - Martin P
AD  - From the *Shire Development LLC, Wayne, PA; daggerCalifornia Clinical Trials Medical 
      Group, Glendale; and double daggerCollaborative Neuroscience Network, Garden Grove, CA.
FAU - Dirks, Bryan
AU  - Dirks B
FAU - Gertsik, Lev
AU  - Gertsik L
FAU - Walling, David
AU  - Walling D
FAU - Stevenson, Annette
AU  - Stevenson A
FAU - Corcoran, Mary
AU  - Corcoran M
FAU - Raychaudhuri, Aparna
AU  - Raychaudhuri A
FAU - Ermer, James
AU  - Ermer J
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Psychopharmacol
JT  - Journal of clinical psychopharmacology
JID - 8109496
RN  - SJT761GEGS (Lisdexamfetamine Dimesylate)
RN  - TZ47U051FI (Dextroamphetamine)
SB  - IM
MH  - Adult
MH  - Cross-Over Studies
MH  - Dextroamphetamine/*administration & dosage/adverse effects/*blood
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Lisdexamfetamine Dimesylate
MH  - Male
MH  - Middle Aged
MH  - Schizophrenia/*blood/*drug therapy
EDAT- 2014/10/14 06:00
MHDA- 2015/07/29 06:00
CRDT- 2014/10/14 06:00
PHST- 2014/10/14 06:00 [entrez]
PHST- 2014/10/14 06:00 [pubmed]
PHST- 2015/07/29 06:00 [medline]
AID - 10.1097/JCP.0000000000000205 [doi]
PST - ppublish
SO  - J Clin Psychopharmacol. 2014 Dec;34(6):682-9. doi: 10.1097/JCP.0000000000000205.