Safety and efficacy of the choline analogue SAR97276 for malaria treatment: results of two phase 2, open-label, multicenter trials in African patients
Posted on 2017-05-04 - 05:00
Abstract Background Malaria remains one of the most important infectious diseases. Treatment options for severe malaria are limited and the choline analogue SAR97276A is a novel chemical entity that was developed primarily as treatment for severe malaria. Before starting clinical investigations in severely ill malaria patients, safety and efficacy of SAR97276A was studied in patients with uncomplicated malaria. Here, we summarize two open-label, multi-center phase 2 trials assessing safety and efficacy of parenterally administered SAR97276A in African adults and children with falciparum malaria. Results Study 1 was conducted in Burkina Faso, Gabon, Benin and Tanzania between August 2008 and July 2009 in malaria patients in an age de-escalating design (adults, children). A total of 113 malaria patients received SAR97276A. Adults were randomized to receive a single dose SAR97296A given either intramuscularly (IM) (0.18 mg/kg) or intravenously (IV) (0.14 mg/kg). If a single dose was not efficacious a second adult group was planned to test a three dose regimen administered IM once daily for 3 days. Single dose SAR97276A showed insufficient efficacy in adults (IM: 20 of 34 cured, 59%; and IV: 23/30 cured, 77%). The 3-day IM regimen showed acceptable efficacy in adults (27/30, 90%) but not in children (13/19, 68%). SAR97276A was well tolerated but no further groups were recruited due lack of efficacy. Study 2 was conducted between October 2011 and January 2012 in Burkina Faso, Gabon and Kenya. SAR97276A administered at a higher dose given IM was compared to artemether–lumefantrine. The study population was restricted to underage malaria patients to be subsequently enrolled in two age cohorts (teenagers, children). Rescue therapy was required in all teenaged malaria patients (8/8) receiving SAR97276A once daily (0.5 mg/kg) for 3 days and in 5 out of 8 teenaged patients treated twice daily (0.25 mg/kg) for 3 days. All patients (4/4) in the control group were cured. The study was stopped, before enrollment of children, due to lack of efficacy but the overall safety profile was good. Conclusions Monotherapy with SAR97276A up to twice daily for 3 days is not an efficacious treatment for falciparum malaria. SAR97276A will not be further developed for the treatment of malaria. Trial registration at clinicaltrials.gov: NCT00739206, retrospectively registered August 20, 2008 for Study 1 and NCT01445938 registered September 26, 2011 for Study 2.
CITE THIS COLLECTION
DataCiteDataCite
3 Biotech3 Biotech
3D Printing in Medicine3D Printing in Medicine
3D Research3D Research
3D-Printed Materials and Systems3D-Printed Materials and Systems
4OR4OR
AAPG BulletinAAPG Bulletin
AAPS OpenAAPS Open
AAPS PharmSciTechAAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität HamburgAbhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)ABI Technik (German)
Academic MedicineAcademic Medicine
Academic PediatricsAcademic Pediatrics
Academic PsychiatryAcademic Psychiatry
Academic QuestionsAcademic Questions
Academy of Management DiscoveriesAcademy of Management Discoveries
Academy of Management JournalAcademy of Management Journal
Academy of Management Learning and EducationAcademy of Management Learning and Education
Academy of Management PerspectivesAcademy of Management Perspectives
Academy of Management ProceedingsAcademy of Management Proceedings
Academy of Management ReviewAcademy of Management Review
Held, Jana; Supan, Christian; Salazar, Carmen; Tinto, Halidou; Bonkian, Léa; Nahum, Alain; et al. (2017). Safety and efficacy of the choline analogue SAR97276 for malaria treatment: results of two phase 2, open-label, multicenter trials in African patients. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.3772109.v1