Safety of AMIZATE® in children

A multi-centre, randomized, double-blind, parallel-arm study was conducted to investigate the safety of AMIZATE® in children (Nesse et al., 2013; Appendix D). A total of 438 children between the ages of 6 to 8, and meeting the criteria for mild (Grade I) or moderate (Grade II) malnutrition according to the Gómez classification of nutritional status (Gómez et al., 1955, 1956), were recruited from 6 government schools in India. The children were randomized to receive 1 of following 3 interventions for 4 months (120 days): a chocolate drink consisting of 60 g of cocoa powder in 120 mL drinking water (placebo); a chocolate drink containing 3 g/day of AMIZATE®; or a chocolate drink containing 6 g/day of AMIZATE®. Each intervention arm included 146 subjects. At each study visit, the subjects were assessed for general health and anthropometric measures were taken. Each adverse event was recorded for the duration, severity, action taken, and date and time of resolution at each study visit, and their relatedness to the test article was assessed by the investigator. Blood and urine samples were collected from the children at the screening visit and at the end of the study, and they were analyzed for the standard hematology, clinical chemistry, and urinalysis parameters.

All of the children enrolled completed the study, and only mild adverse events (e.g., vomiting, stomach upset, nausea, loss of appetite, fever, headache, cold and cough) were observed in some of the participants. There was no significant difference in the number of subjects reporting an adverse event across the intervention groups (i.e., 14, 13, and 9 subjects in the placebo, 3 g/day, and 6 g/day dose of AMIZATE®, respectively), or in the number of adverse events reported (i.e., 15, 18, and 16 events in the placebo, 3 g/day, and 6 g/day dose of AMIZATE®, respectively).

In all of the intervention arms, the mean body weight was significantly higher at the end of the 4-month study compared to baseline (controls: +0.753 kg; 3 g/day AMIZATE®: +1.105 kg; 6 g/day AMIZATE®: +1.662 kg). The mean height of children administered the 6 g/day of AMIZATE® was significantly increased at the end of the study compared to baseline (+0.041 cm; p <0.05), while no significant changes in body height were observed in children receiving the 3 g/day dose or the placebo control over the course of the study. Therefore, administration of AMIZATE® did not result in any adverse effects on rate of body growth in this study. Administration of either 3 g/day or 6 g/day of AMIZATE® also did not significantly alter hematology or clinical chemistry parameters compared to those observed in the placebo control group. Routine urinalysis did not reveal any abnormalities that were attributable to the consumption of AMIZATE®. Overall, administration of AMIZATE® at doses up to 6 g/day for 4 months was well tolerated, and no adverse events were reported that could be attributed to its administration.