Table 1 Key clinical studies evaluating the safety of the six-dose regimen of AL.

van Vugt et al 1999 [6]

Randomized, double-blind

Six-dose regimen

Adults & children (>2 years)

120 out of 359^†

Thailand

Possible treatment-related AEs were reported by 16.7% of patients. These AEs could also have been related to malaria and were mild or moderate in severity. No neurological or cardiac safety issues were identified.

van Vugt et al 2000 [7]

Randomized, open-label

MAS*

Adults & children (≥ 2 years)

150 out of 200

Thailand

Most AEs considered drug-related were mild or moderate in severity. Possibly related AEs occurred at a frequency of 22% in the AL group compared with 46% in the MAS group. In the AL group 6% had nervous system AEs compared with 34% in the MAS group (relative risk: 0.18; p < 0.0001). Gastrointestinal AEs were also less frequent in the AL compared with MAS groups (12.7% vs 26%; relative risk: 0.49; p < 0.043). No ECG abnormalities were identified.

Lefèvre et al 2001 [8]

Randomized, open-label

MAS*

Adults & adolescents (≥ 12 years)

164 out of 219

Thailand

Nearly 90% in both treatment groups reported treatment emergent signs/symptoms and these were of mild or moderate severity. 18.3% of patients taking AL and 21.8% of patients taking MAS reported gastrointestinal symptoms while 27.4% and 16.4% of patients, respectively reported headache, dizziness and sleep disorder. Skin reactions were reported by 4.9% of patients taking AL and 3.6% of patients taking MAS. There were no cardiac complications and no significant renal, hepatic or haemopoietic dysfunction.

Falade et al 2005 [9]

Open-label

Nil

Infants & children (5 to 25 kg)

310

Kenya, Tanzania, Nigeria

The most commonly reported AEs were cough, anaemia, anorexia, vomiting and diarrhoea. Some differences in AEs were seen in the different body weight groups but as these were generally mild, differences were not considered clinically relevant. Only one patient had a SAE (urticaria) that was considered to be related to study medication and this event resolved when treatment was withdrawn. No cardiac safety issues were identified and there were no significant abnormal laboratory values associated with AL treatment.

Hatz et al 2008 [10]

Open-label

Nil

Adult, non-immune travellers

165

EU, Colombia

Treatment was well tolerated and most AEs were mild or moderate in severity. The most frequently reported AEs were headache, insomnia, diarrhoea, nausea and vomiting and these AEs (along with anorexia, vertigo and chills) were most probably related to signs and symptoms of malaria. No allergic reactions were reported in any of the patients. There were few SAEs and none of these were considered related to AL. No significant effects were observed during ECGs and there were no significant effects seen with regard to laboratory parameters.

Abdulla et al 2008 [11]

Randomized, investigator-blind

Dispersible formulation of AL

Infants & children (5 to <35 kg)

452 out of 899

Kenya, Tanzania, Mali, Benin, Mozambique

There was no difference in the pattern of AEs seen in patients who received treatment with crushed AL tablets compared with those who received the dispersible formulation. No new or unexpected AEs were identified and the most commonly reported AEs were also related to malaria. The most common drug-related AE was vomiting; this was more frequently reported in the lowest weight category. The number of SAEs was low (1-2% in both groups) and most of these were infections. There were no signs of ototoxicity. There were no clinically relevant findings or differences between study groups for ECG assessments, vital signs, or laboratory parameters.