Table 1 Characteristics of the studies [10,11,12, 15]

Phase and design

Phase 2, open-label dose-escalation study

Phase 3, multi-centre, comparative, open-label, parallel-group, controlled clinical trial

Phase 3b/4, randomised, multicentre, open-label, longitudinal, controlled trial

Single-arm, open-label, cohort event monitoring study

Dates

Jun 2006 to Dec 2006

Nov 2007 to Sep 2008

Oct 2011 to Feb 2016

Jun 2017 to Apr 2019

Location and setting

One clinical unit in Gabon

Seven centres in Burkina Faso, Democratic Republic of Congo, Gabon, Côte d’Ivoire, Kenya, Mali, and the Philippines

Seven centres in Burkina Faso, Guinea, and Mali

Six centres in Cameroon, Democratic Republic of Congo, Gabon, Côte d’Ivoire, and Republic of Congo

Patients

Aged 2–14 years, body weight 10–40 kg

Aged ≤ 12 years, bodyweight ≥ 5 to < 25 kg

Adults and children aged 6 months and older, bodyweight ≥ 5 kg

Any age, bodyweight ≥ 5 kg

Treatments

Pyronaridine-artesunate 6:2 mg/kg, 9:3 mg/kg and 21:4 mg/kg tablets; 9:3 mg/kg granules

Pyronaridine–artesunate granules versus artemether–lumefantrine crushed tablets

Pyronaridine–artesunate (tablets or granules) or dihydroartemisinin–piperaquine (tablets or crushed tablets) versus either artesunate–amodiaquine (tablets or dissolved tablets) or artemether–lumefantrine (tablets or dispersible tablets)

Pyronaridine–artesunate (tablets and granules)

Primary outcomes

Tolerability, safety, and pharmacokinetics, PCR-adjusted ACPR at day 28

Day-28 PCR-adjusted ACPR > 90%, safety

2-year incidence rate of all malaria episodes; day 28 and 42 ACPR in uncomplicated malaria, safety

Hepatic event incidence, clinical effectiveness (see text for definitions)