Efficacy of ArTiMist™ in Children

• Quinine (Drug): 20 mg/kg intravenous quinine loading dose, followed by 10 mg/kg intravenously every 8 hours until resumption of normal oral therapy
• Artemether (Drug), also known as ArTiMist™: Artemether sublingual spray 3 mg/kg at protocol specified timepoints until resumption of normal oral therapy

Primary outcomes

• Parasitological Success Defined as a Reduction in Parasite Count of ≥ 90% of Baseline at 24 Hours After the First Dose [24 hours after first dose]
• Time for Parasite Count to Fall by 90% PCT(90) [3h (hours), 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h]: The time taken for the parasite count to fall 90% from baseline
• Time for Parasite Count to Fall by 50% PCT(50) [3 h (hours) , 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h]: The time taken for the parasite count to fall 50% from baseline

Secondary outcomes

• Parasite Clearance Time [3h (hours), 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h]: Time in hours from the initiation of therapy until the first of two successive parasite-negative smears were obtained
• Parasite Reduction Ratio (PRR) at 24 h (Hours) After the First Dose [24 hours after first dose]: Reduction in parasitaemia from baseline at 24 h after the first dose of study medication
• Parasite Reduction Ratio (PRR) at 12 Hours After the First Dose [12 h (hours) after first dose]: Reduction in parasitaemia from baseline at 12 hours after the first dose of study medication

Sex: All

Inclusion Criteria:

1. The patient's parent or attendant relative has provided informed consent and the patient has assented (where relevant) to participation in the trial
2. The patient is a child that weighs between 5 and 15 kg (kilogram)
3. The patient has falciparum malaria as evidenced by

   1. Thick or thin blood smears of > 500 P falciparum per mcl (microlitre)(patients with mixed infections may be included provided >500 P Falciparum /mcl) and /or
   2. Positive RDT (rapid diagnostic test)for malaria
4. The patient has either

   1. severe or complicated malaria as determined by the Investigator based on the WHO criteria for severity, or
   2. the patient has uncomplicated malaria but is unable to tolerate oral medication as a result of gastrointestinal complications such as vomiting or diarrhoea.

Exclusion Criteria:

1. Attending relative or parent does not provide informed consent for participation, or the child if capable does not assent to participation in the trial.
2. Ability to tolerate oral therapy
3. Patient has received any treatment with an artemisinin or quinine in the last 24 hours
4. Patient has evidence of significant co-infections (this does not include mixed Plasmodium infections).
5. Patient is allergic or intolerant to artemisinins.

Participant flow

Outcome results

• Parasitological Success Defined as a Reduction in Parasite Count of ≥ 90% of Baseline at 24 Hours After the First Dose (Primary), Number, participants: ArTiMist 14; Intravenous Quinine 10 (p 0.17)
• Parasite Clearance Time (Secondary), Mean, Hours: ArTiMist 35.7 +/- 41.97; Intravenous Quinine 51.2 +/- 79.04
• Time for Parasite Count to Fall by 90% PCT(90) (Primary), Mean, hours: ArTiMist 17.6 +/- 7.34; Intravenous Quinine 19.8 +/- 13.59 (p 0.70)
• Parasite Reduction Ratio (PRR) at 24 h (Hours) After the First Dose (Secondary), Median, Percent reduction: ArTiMist 100.0 (77 to 100); Intravenous Quinine 96.9 (53 to 100)
• Time for Parasite Count to Fall by 50% PCT(50) (Primary), Mean, hours: ArTiMist 12.0 +/- 6.48; Intravenous Quinine 10.8 +/- 7.42 (p 0.76)
• Parasite Reduction Ratio (PRR) at 12 Hours After the First Dose (Secondary), Median, Percent reduction: ArTiMist 79.6 (-220 to 100); Intravenous Quinine 75.9 (-58 to 100)

Adverse events

Time frame: Adverse events were collected from the start of the study (01 December 2009) to the last study follow up visit on 19 January 2010

Serious adverse events by term

Other adverse events by term

• Results publication: Bendel D, Rulisa S, Ansah P, Sirima S. Efficacy of a novel sublingual spray formulation of artemether in African children with Plasmodium falciparum malaria. Antimicrob Agents Chemother. 2015 Nov;59(11):6930-8. doi: 10.1128/AAC.00243-15. Epub 2015 Aug 24. PMID 26303805

• Daryl Bendel, MBChB MBA Dip Pharm Med MFPM, Study director, Xidea Solutions Limited