@article{Held2017-eo,

title = {Safety and efficacy of the choline analogue SAR97276 for  malaria treatment: results of two phase 2, open-label,  multicenter trials in African patients},

author = {Jana Held and Christian Supan and Carmen L Ospina Salazar and Halidou Tinto and L\'{e}a Nad`ege Bonkian and Alain Nahum and Ali Si\'{e} and Salim Abdulla and Cathy Cantalloube and Elhadj Djeriou and Marielle Bouyou-Akotet and Bernhards Ogutu and Benjamin Mordm\"{u}ller and Andrea Kreidenweiss and Mohamadou Siribie and Sodiomon B Sirima and Peter G Kremsner},

doi = {10.1186/s12936-017-1832-x},

issn = {1475-2875},

year  = {2017},

date = {2017-05-01},

urldate = {2017-05-01},

journal = {Malar. J.},

volume = {16},

number = {1},

pages = {188},

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.},

keywords = {Africa; Choline analogue; Malaria; P. falciparum; Phase 2;   SAR97276A},

pubstate = {published},

tppubtype = {article}

}