PMID- 17577466
OWN - NLM
STAT- MEDLINE
DCOM- 20070803
LR  - 20220317
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 29
IP  - 3
DP  - 2007 Mar
TI  - Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children 
      with attention-deficit/hyperactivity disorder: a phase III, multicenter, 
      randomized, double-blind, forced-dose, parallel-group study.
PG  - 450-63
AB  - BACKGROUND: Lisdexamfetamme dimesylate (LDX) is a therapeutically inactive 
      amphetamine prodrug. It was developed with the goal of providing an extended 
      duration of effect that is consistent throughout the day, with a reduced 
      potential for abuse, overdose toxicity, and drug tampering. Following ingestion, 
      the pharmacologically active d-amphetamine molecule is gradually released by 
      rate-limited hydrolysis. OBJECTIVES: The aims of this study were to assess the 
      efficacy and tolerability of LDX in school-aged children with 
      attention-deficit/hyperactivity disorder (ADHD) treated in the community, and to 
      characterize the duration of action of LDX compared with placebo. METHODS: This 
      Phase III, multicenter, randomized, double-blind, forced-dose, parallel-group 
      study was conducted at 40 centers across the United States. Male and female 
      children aged 6 to 12 years with ADHD were randomly assigned to receive LDX 30, 
      50, or 70 mg with forced-dose titration, or placebo, PO QD for 4 weeks. Efficacy 
      was assessed using the ADHD Rating Scale Version IV (ADHD-RS-IV), the Conners' 
      Parent Rating Scale (CPR'), and the Clinical Global Impression of Improvement 
      scale. Tolerability was assessed throughout the study. RESULTS: Of the 290 
      randomized patients (201 boys, 89 girls; mean [SD] age, 9 [1.8] years), 230 
      completed the trial (LDX 30 mg, n=56; LDX 50 mg, n=60; LDX 70 mg, n=60; and 
      placebo, n=54). The most common reasons for study discontinuation (n=60) were 
      lack of efficacy (LDX 30 mg, 1%; LDX 50 mg, 0%; LDX 70 mg, 1 %; and placebo, 17%) 
      and adverse events (AEs) (LDX 30 mg, 9%; LDX 50 mg, 5%; LDX 70 mg, 14%; and 
      placebo, 1%). Significant improvements in ADHD-RS-IV scores were seen with all 
      doses of LDX compared with placebo (all, P<0.001), and in CPRS scores with all 
      LDX doses versus placebo throughout the day (all, P<0.001 for all comparisons). 
      Efficacy was observed by the first week of treatment, and improvements were 
      observed throughout the day up to approximately 6 PM. The most frequently 
      reported AEs among patients receiving LDX were typical of amphetamine products: 
      decreased appetite (39% with active treatment vs 4% with placebo), insomnia (19% 
      vs 3%), upper abdominal pain (12% vs 6%), headache (12% vs 10%), irritability 
      (10% vs 0%), vomiting (9% vs 4%), weight decrease (9% vs 1%), and nausea (6% vs 
      3%); most were mild to moderate and occurred in the first week. CONCLUSION: In 
      this population of children with ADHD, treatment once daily with the prodrug LDX 
      at doses of 30 to 70 mg appeared to be effective and had a tolerability profile 
      similar to those of currently marketed extended-release stimulants.
FAU - Biederman, Joseph
AU  - Biederman J
AD  - Department of Pediatric Psychopharmacology, Massachusetts General Hospital, 
      Boston, Massachusetts 02114, USA. jbiederman@partners.org
FAU - Krishnan, Suma
AU  - Krishnan S
FAU - Zhang, Yuxin
AU  - Zhang Y
FAU - McGough, James J
AU  - McGough JJ
FAU - Findling, Robert L
AU  - Findling RL
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Delayed-Action Preparations)
RN  - K3Z4F929H6 (Lysine)
RN  - SJT761GEGS (Lisdexamfetamine Dimesylate)
RN  - TZ47U051FI (Dextroamphetamine)
SB  - IM
MH  - Administration, Oral
MH  - Attention Deficit Disorder with Hyperactivity/*drug therapy
MH  - Central Nervous System Stimulants/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Child
MH  - Delayed-Action Preparations
MH  - Dextroamphetamine/administration & dosage/adverse effects/*therapeutic use
MH  - Diagnostic and Statistical Manual of Mental Disorders
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Lisdexamfetamine Dimesylate
MH  - Lysine
MH  - Male
MH  - Treatment Outcome
EDAT- 2007/06/20 09:00
MHDA- 2007/08/04 09:00
CRDT- 2007/06/20 09:00
PHST- 2007/01/31 00:00 [accepted]
PHST- 2007/06/20 09:00 [pubmed]
PHST- 2007/08/04 09:00 [medline]
PHST- 2007/06/20 09:00 [entrez]
AID - S0149-2918(07)80083-X [pii]
AID - 10.1016/s0149-2918(07)80083-x [doi]
PST - ppublish
SO  - Clin Ther. 2007 Mar;29(3):450-63. doi: 10.1016/s0149-2918(07)80083-x.