title: Antimalarial efficacy of a quantified extract of Nauclea pobeguinii stem bark in human adult volunteers with diagnosed uncomplicated falciparum malaria. Part 1: a clinical phase IIA trial.
abstract: The aim of this phase IIA clinical trial was to assess the efficacy of an 80 % ethanolic quantified extract (containing 5.6 % strictosamide as the putative active constituent) from Nauclea pobeguinii stem bark denoted as PR 259 CT1 in a small group of adult patients diagnosed with uncomplicated falciparum malaria. Results obtained from a phase I clinical trial on healthy male volunteers indicated that the oral administration during meals of two 500 mg capsules three times daily (each eight hours) during seven days was well tolerated and showed only mild and self-resolving adverse effects. This PR 259 CT1 drug regimen was obtained by mathematical conversion of animal doses obtained in several in vivo studies in mice to human equivalent doses as in falciparum malaria patients. The phase IIA study was an open cohort study in eleven appraisable adult patients suffering from proven Plasmodium falciparum malaria. The study was specifically designed to assess the efficacy of PR 259 CT1 administered with a dose regimen of two 500 mg capsules three times daily for three days, followed by outpatient treatment of one 500 mg capsule three times daily for the next four days, in order to prove that this therapeutic dose, which was calculated from animal doses, was effective to treat adult malaria patients and consequently useful for a future Phase IIB clinical trial. This study would then substitute a dose-escalating trial, which in general is used to find the appropriate dose for clinical studies. The phase IIA clinical trial was carried out according to the WHO 2003 14-day test, and the results revealed that all eleven patients were completely cleared of parasitemia and fever on days 3, 7, and 14 except for one patient, who experienced a recurrence of parasitemia at days 7 until 14. Besides this adequate clinical and parasitological response (ACPR), this trial also demonstrated that PR 259 CT1 was well tolerated with only mild and self-resolving adverse effects including fatigue and headache, which were in accordance with those found in the phase I clinical trial. Moreover, all symptoms progressively disappeared, and no symptoms were observed on day 14. Although the number of patients included in this study was rather limited, the statistical analysis nevertheless suggested the efficacy and tolerability of PR 259 CT1, which indicated that this herbal medicinal product might be considered as a putative candidate for a large scale clinical trial.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Kinshasa, Kinshasa XI, Democratic Republic of Congo.
authors.forename: Kahunu
authors.initials: K
authors.lastname: Mesia
authors.forename: Lutete
authors.initials: L
authors.lastname: Tona
authors.forename: Ma Miezi
authors.initials: MM
authors.lastname: Mampunza
authors.forename: Nsengi
authors.initials: N
authors.lastname: Ntamabyaliro
authors.forename: Tsobo
authors.initials: T
authors.lastname: Muanda
authors.forename: Tamfum
authors.initials: T
authors.lastname: Muyembe
authors.forename: Kanyanga
authors.initials: K
authors.lastname: Cimanga
authors.forename: Jozef
authors.initials: J
authors.lastname: Totté
authors.forename: Tony
authors.initials: T
authors.lastname: Mets
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Vlietinck
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008517:Phytotherapy / Q000379:methods*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D018547:Plant Stems / Q000737:chemistry; D019666:Rubiaceae / Q000737:chemistry*; D014748:Vinca Alkaloids / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D010936:Plant Extracts; D014748:Vinca Alkaloids; C539462:strictosamide