Planta Med 2012; 78(3): 211-218
DOI: 10.1055/s-0031-1280359
Clinical Study
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

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

Kahunu Mesia1 , Lutete Tona1 , Ma Miezi Mampunza2 , Nsengi Ntamabyaliro1 , Tsobo Muanda1 , Tamfum Muyembe2 , Kanyanga Cimanga1 , 3 , Jozef Totté3 , Tony Mets4 , Luc Pieters3 , Arnold J. Vlietinck3
  • 1Faculty of Pharmaceutical Sciences, University of Kinshasa, Kinshasa XI, Democratic Republic of Congo
  • 2Faculty of Medicine, University of Kinshasa, Kinshasa XI, Democratic Republic of Congo
  • 3Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
  • 4Faculty of Medicine and Pharmacy, Free University of Brussels (VUB), Brussels, Belgium
Further Information

Publication History

received May 24, 2011 revised Sept. 15, 2011

accepted October 25, 2011

Publication Date:
17 November 2011 (online)

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.

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Dr. Kanyanga Cimanga

Department of Pharmaceutical Sciences
University of Antwerp

Universiteitsplein 1

2610 Antwerp

Belgium

Phone: +32 32 65 27 33

Fax: +32 32 56 27 09

Email: kanyanga.cimanga@ua.ac.be