Quinine administered intravenously, 20 mg/kg loading dose followed by 10 mg/kg every eight hours

Time for parasite counts to fall by 50%

The percentage reduction in parasite counts 24 hours after first dose

The percentage reduction in parasite counts 12 hours after first dose

Time in hours from the initiation of therapy until the disappearance of fever (tympanic temperature < 38.0) that lasted at least 24 hours.

The complete resolution of clinical signs and symptoms, malaria-related laboratory abnormalities, and elimination of asexual parasites by Day 7, with no recurrence up to Day 28 (+/- 2 days), and the 48h parasite count to be < 25% of baseline with no clinical deterioration

Early treatment failure is indicated by one or more of the following:

• Parasite count on Day 2 > Day 0, irrespective of temperature
• Parasite count on Day 3 > 0 with tympanic temperature ≥ 38.0°C
• Parasite count on Day 3 ≥ 25% of baseline
• Administration of rescue antimalarial treatment

• Signs of severe malaria on any day between Day 4 and Day 28 in the presence of parasitaemia, without previously meeting any of the criteria of early treatment failure
• Presence of parasitaemia and tympanic temperature ≥ 38.0°C (or history of fever), on any day between Day 4 and Day 28, without previously meeting any of the criteria of early treatment failure

o Parasitaemia on any day from Day 7 to Day 28 and tympanic temperature ≤ 38.0°C

Time in hours to return to full consciousness (Blantyre Coma Scale = 5), if level of consciousness is reduced (Blantyre Coma Scale <5) prior to dosing or within 24hours of first dosing.

For the Blantyre Coma Scale

Total - maximum 5, eye movement - maximum 1, best motor response - maximum 2, best verbal response - maximum 2

Time in hours to return to normal per os status. Normal per os was when the investigator considered the patient to be able to eat and drink normally.

A loading dose of 20 mg/kg was given over four hours and thereafter 10 mg/kg was given every eight hours until the subject was able to swallow. Thereafter, patients were given quinine syrup or crushed tablets (10 mg/kg every eight hours) or another suitable treatment to ensure they received at least seven days of therapy, or be converted to another suitable treatment or a suitable course of combination therapy, in accordance with national drugs policy where applicable

Total of all reporting groups

Blantyre Coma scale scores out of 5, full consciousness, by adding the scores of the following 3 domains. Any score ≤ 4 is considered abnormal,

Eye Movement

1 Watches or follows 0 Fails to watch or follow

Best Motor Response 2 Localizes painful stimulus 1 Withdraws limb from painful stimulus 0 No response or inappropriate response

Best Verbal Response 2 Cries appropriately with pain, or if verbal, speaks

1 Moan or abnormal cry with pain 0 No vocal response with pain

Parasite clearance time (PCT). Time in hours from the initiation of therapy until the first of two successive parasite negative smears (zero parasite counts) are obtained

Time for parasite counts to fall by 90%

Time for parasite counts to fall by 50%

The percentage reduction in parasite counts 24 hours after first dose

The percentage reduction in parasite counts 12 hours after first dose

Time in hours from the initiation of therapy until the disappearance of fever (tympanic temperature < 38.0) that lasted at least 24 hours.

The complete resolution of clinical signs and symptoms, malaria-related laboratory abnormalities, and elimination of asexual parasites by Day 7, with no recurrence up to Day 28 (+/- 2 days), and the 48h parasite count to be < 25% of baseline with no clinical deterioration

For some subjects, this endpoint was not evaluable and/or not all data was received.

Early treatment failure is indicated by one or more of the following:

• Parasite count on Day 2 > Day 0, irrespective of temperature
• Parasite count on Day 3 > 0 with tympanic temperature ≥ 38.0°C
• Parasite count on Day 3 ≥ 25% of baseline
• Administration of rescue antimalarial treatment

• Signs of severe malaria on any day between Day 4 and Day 28 in the presence of parasitaemia, without previously meeting any of the criteria of early treatment failure
• Presence of parasitaemia and tympanic temperature ≥ 38.0°C (or history of fever), on any day between Day 4 and Day 28, without previously meeting any of the criteria of early treatment failure

Parasitological success defined as a reduction in parasite count of ≥ 90% of baseline at 24 hours after the first dose

The Per Protocol (PP) population included the subjects in the MITT population who had received at least 80% of doses up to the time of discharge from the hospital, had evaluable data up to and including Day 28 and had no major protocol violations.

o Parasitaemia on any day from Day 7 to Day 28 and tympanic temperature ≤ 38.0°C

Time in hours to return to full consciousness (Blantyre Coma Scale = 5), if level of consciousness is reduced (Blantyre Coma Scale <5) prior to dosing or within 24hours of first dosing.

For the Blantyre Coma Scale

Total - maximum 5, eye movement - maximum 1, best motor response - maximum 2, best verbal response - maximum 2

Time in hours to return to normal per os status. Normal per os was when the investigator considered the patient to be able to eat and drink normally.