PMID- 17213921
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20070813
LR  - 20220310
IS  - 1555-5887 (Electronic)
IS  - 1555-5887 (Linking)
VI  - 2
IP  - 1
DP  - 2007 Jan 5
TI  - Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and 
      chloroquine in healthy volunteers.
PG  - e6
LID - e6
AB  - OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an 
      investigational aminoquinoline active against multidrug-resistant malaria 
      parasites (AQ-13), including its effects on the QT interval, and (2) whether it 
      has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. 
      DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and 
      CQ in healthy volunteers. Randomizations were performed at each step after 
      completion of the previous dose. SETTING: Tulane-Louisiana State 
      University-Charity Hospital General Clinical Research Center in New Orleans. 
      PARTICIPANTS: 126 healthy adults 21-45 years of age. INTERVENTIONS: 10, 100, 300, 
      600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of 
      AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), 
      pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, 
      hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose 
      tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) 
      tract-related symptoms were the most common AEs. Although symptoms were more 
      frequent with AQ-13, the numbers of volunteers who experienced symptoms with 
      AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 
      10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 
      14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. 
      However, AQ-13 was cleared more rapidly than CQ (respectively, median oral 
      clearance 14.0-14.7 l/h versus 9.5-11.3 l/h; p < or = 0.03). QTc prolongation was 
      greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval 
      [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 
      0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. 
      CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 
      and CQ, and similar linear pharmacokinetics.
FAU - Mzayek, Fawaz
AU  - Mzayek F
AD  - Center for Infectious Diseases, Tulane University Health Sciences Center, New 
      Orleans, Louisiana, United States of America.
FAU - Deng, Haiyan
AU  - Deng H
FAU - Mather, Frances J
AU  - Mather FJ
FAU - Wasilevich, Elizabeth C
AU  - Wasilevich EC
FAU - Liu, Huayin
AU  - Liu H
FAU - Hadi, Christiane M
AU  - Hadi CM
FAU - Chansolme, David H
AU  - Chansolme DH
FAU - Murphy, Holly A
AU  - Murphy HA
FAU - Melek, Bekir H
AU  - Melek BH
FAU - Tenaglia, Alan N
AU  - Tenaglia AN
FAU - Mushatt, David M
AU  - Mushatt DM
FAU - Dreisbach, Albert W
AU  - Dreisbach AW
FAU - Lertora, Juan J L
AU  - Lertora JJ
FAU - Krogstad, Donald J
AU  - Krogstad DJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - M01 RR005096/RR/NCRR NIH HHS/United States
GR  - U01 CI000211/CI/NCPDCID CDC HHS/United States
PT  - Journal Article
DEP - 20070105
PL  - England
TA  - PLoS Clin Trials
JT  - PLoS clinical trials
JID - 101257529
PMC - PMC1764434
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2007/01/11 09:00
MHDA- 2007/01/11 09:01
PMCR- 2007/01/01
CRDT- 2007/01/11 09:00
PHST- 2006/05/11 00:00 [received]
PHST- 2006/11/03 00:00 [accepted]
PHST- 2007/01/11 09:00 [pubmed]
PHST- 2007/01/11 09:01 [medline]
PHST- 2007/01/11 09:00 [entrez]
PHST- 2007/01/01 00:00 [pmc-release]
AID - 06-PLCT-CT-00032R2 [pii]
AID - 10.1371/journal.pctr.0020006 [doi]
PST - epublish
SO  - PLoS Clin Trials. 2007 Jan 5;2(1):e6. doi: 10.1371/journal.pctr.0020006.