Sponsor study identifier
interventional
36
1 country
1
Study Start
May 1, 2017
Actual (reported)Primary Completion
March 1, 2018
Actual (reported)Study Completion
March 1, 2018
Actual (reported)To investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers. The specific aim is the comparative evaluation of the metabolism, pharmacokinetic behavior, and tolerability of the isomers of PQ (RPQ and SPQ and the racemic mixture RSPQ) in normal healthy human volunteers.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
March 1, 2018
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
July 21, 2016
Actual (reported)September 13, 2016
Actual (reported)May 1, 2017
Actual (reported)March 1, 2018
Actual (reported)March 1, 2018
Actual (reported)Primary outcome: Plasma concentration of parent primaquine and carboyprimaquine following a single dose treatment with primaquine (racemate or enantiomers) not to exceed 45 mg
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
between 0-24 Hours
Area Under Curve (AUC) for primaquine up to 24 hours after the primaquine administration
between 0-24 hours
Maximum concentration (Cmax) for primaquine up to 24 hours after the primaquine administration
between 0-24 hours
Area Under Curve (AUC) for carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration
between 0-24 hours
Maximum concentration of carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration
between 0-24 hours
Maximum concentration of selected metabolites primaquine (other than carboxyprimaquine) up to 24 hours after primaquine administration
between 0-24 hours
Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers. Cohort 1 (Low Dose Level)- single dose of 15 mg of S-Primaquine and 15 mg of R-Primaquine compared to 30 mg RS-Primaquine over 24 hours. Participants will cross-over after a one week wash-out period.
Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers. Cohort 2 (High Dose Level)-single dose of 22.5 mg of S-Primaquine and 22.5 mg of R-Primaquine compared to 45 mg RS-Primaquine over 24 hours. Participants will cross-over among the treatment arms following a one week wash-out period between each.
Cohort 1: Eighteen individuals (6 per group) Cohort 2: Eighteen individuals (6 per group) Group 1-15 mg of S-Primaquine followed by one-week washout, 15 mg of R-Primaquine followed by one week washout, and 30 mg of RS-Primaquine. Group 2- 15 mg of R-Primaquine followed by one-week washout, 30 mg of RSPQ followed by one week washout, and 15 mg of SPQ. Group 3- 30 mg of RS-Primaquine followed by one week washout,15 mg of SPQ followed by a one week washout, and 15 mg of RPQ.
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
University of Mississippi
Oxford, Mississippi, 38677, United States
Avula B, Tekwani BL, Chaurasiya ND, Nanayakkara NP, Wang YH, Khan SI, Adelli VR, Sahu R, Elsohly MA, McChesney JD, Khan IA, Walker LA. Profiling primaquine metabolites in primary human hepatocytes using UHPLC-QTOF-MS with 13C stable isotope labeling. J Mass Spectrom. 2013 Feb;48(2):276-85. doi: 10.1002/jms.3122.
Avula B, Khan SI, Tekwani BL, Nanayakkara NP, McChesney JD, Walker LA, Khan IA. Analysis of primaquine and its metabolite carboxyprimaquine in biological samples: enantiomeric separation, method validation and quantification. Biomed Chromatogr. 2011 Sep;25(9):1010-7. doi: 10.1002/bmc.1557. Epub 2010 Nov 5.
Babu L Tekwani, Ph.D
University of Mississippi Medical Center
36 participants (actual enrollment reported by the registry).
First Submitted
July 21, 2016
First Posted
September 13, 2016
Study Start
May 1, 2017
Actual (reported)Trial to Evaluate the Safety, Immunogenicity, and Efficacy of Malaria Infection in Malaria Naïve Adults
Contact the study team to confirm eligibility.
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Fasinu PS, Tekwani BL, Nanayakkara NP, Avula B, Herath HM, Wang YH, Adelli VR, Elsohly MA, Khan SI, Khan IA, Pybus BS, Marcsisin SR, Reichard GA, McChesney JD, Walker LA. Enantioselective metabolism of primaquine by human CYP2D6. Malar J. 2014 Dec 17;13:507. doi: 10.1186/1475-2875-13-507.
Fasinu PS, Avula B, Tekwani BL, Nanayakkara NP, Wang YH, Bandara Herath HM, McChesney JD, Reichard GA, Marcsisin SR, Elsohly MA, Khan SI, Khan IA, Walker LA. Differential kinetic profiles and metabolism of primaquine enantiomers by human hepatocytes. Malar J. 2016 Apr 19;15:224. doi: 10.1186/s12936-016-1270-1.
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Nanayakkara NP, Ager AL Jr, Bartlett MS, Yardley V, Croft SL, Khan IA, McChesney JD, Walker LA. Antiparasitic activities and toxicities of individual enantiomers of the 8-aminoquinoline 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline succinate. Antimicrob Agents Chemother. 2008 Jun;52(6):2130-7. doi: 10.1128/AAC.00645-07. Epub 2008 Mar 31.
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Potter BM, Xie LH, Vuong C, Zhang J, Zhang P, Duan D, Luong TL, Bandara Herath HM, Dhammika Nanayakkara NP, Tekwani BL, Walker LA, Nolan CK, Sciotti RJ, Zottig VE, Smith PL, Paris RM, Read LT, Li Q, Pybus BS, Sousa JC, Reichard GA, Marcsisin SR. Differential CYP 2D6 metabolism alters primaquine pharmacokinetics. Antimicrob Agents Chemother. 2015 Apr;59(4):2380-7. doi: 10.1128/AAC.00015-15. Epub 2015 Feb 2.
Pybus BS, Marcsisin SR, Jin X, Deye G, Sousa JC, Li Q, Caridha D, Zeng Q, Reichard GA, Ockenhouse C, Bennett J, Walker LA, Ohrt C, Melendez V. The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J. 2013 Jun 20;12:212. doi: 10.1186/1475-2875-12-212.
Saunders D, Vanachayangkul P, Imerbsin R, Khemawoot P, Siripokasupkul R, Tekwani BL, Sampath A, Nanayakkara NP, Ohrt C, Lanteri C, Gettyacamin M, Teja-Isavadharm P, Walker L. Pharmacokinetics and pharmacodynamics of (+)-primaquine and (-)-primaquine enantiomers in rhesus macaques (Macaca mulatta). Antimicrob Agents Chemother. 2014 Dec;58(12):7283-91. doi: 10.1128/AAC.02576-13. Epub 2014 Sep 29.
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Vasquez-Vivar J, Augusto O. Hydroxylated metabolites of the antimalarial drug primaquine. Oxidation and redox cycling. J Biol Chem. 1992 Apr 5;267(10):6848-54.
Primary Completion
March 1, 2018
Actual (reported)Study Completion
March 1, 2018
Actual (reported)Last Updated
May 15, 2018
Record last verified: 2018-05
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