Studies of a Candidate Aminoquinoline Antimalarial (AQ-13)

Phase 2 Proof of Concept Study of a Candidate Aminoquinoline Antimalarial (AQ-13)

This is an initial efficacy study of a candidate antimalarial in human subjects with uncomplicated malaria caused by the most common and most important parasite in Africa (Plasmodium falciparum). This study will enroll 66 adult Malian males with uncomplicated P. falciparum malaria and randomize them to treatment with 1750 mg of the investigational drug (AQ-13) by mouth over 3 days or the current standard treatment, which is 2 doses of Coartem twice daily for 3 days. The hypothesis underlying this study is that AQ-13 will be similarly effective to Coartem for the treatment of uncomplicated P. falciparum malaria due to both chloroquine-susceptible and chloroquine-resistant parasites. Funding Source - FDA Office of Orphan Product Development (OOPD).

This is an initial efficacy study (Phase 2 Proof of Concept Study) of a candidate antimalarial in human subjects with uncomplicated malaria caused by the most common and most important parasite in Africa (Plasmodium falciparum). This study will enroll 66 adult Malian males with uncomplicated P. falciparum malaria and randomize them to treatment with 1750 mg of the investigational drug (AQ-13) by mouth over 3 days or the current standard treatment, which is 80 mg of artemether and 480 mg of lumefantrine twice daily for 3 days. The hypothesis underlying this study is that AQ-13 will be similarly effective to Coartem for the treatment of uncomplicated P. falciparum malaria due to both chloroquine-susceptible and chloroquine-resistant parasites.

Inclusion Criteria

1. Adult Malian males ≥ 18 years of age,
2. Uncomplicated malaria with ≥ 2,000 asexual P. falciparum parasites per ul, and
3. Informed consent obtained and signed.

Exclusion Criteria

1. Severe or complicated malaria (including temperature ≥ 40o C),
2. ≥ 100,000 asexual parasites per ul of blood,
3. Anemia or other laboratory results (other than malaria) that require treatment (e.g., Hb ≤ 7 gm/dL, K+ ≤ 3.5 millimolar (mM), BP ≥ 140/90),
4. Seizures or impaired consciousness,
5. Recent antimalarial treatment by history (within ≤ 2 weeks),
6. Chronic medications (including inducers of Cytochrome P450 3A4 [CYP3A4] activity such as rifampin and nevirapine),
7. Ventricular or atrial arrhythmias, or second or third degree heart block on the screening ECG or Holter recording,
8. Infection with other plasmodial species on the blood smear (P. ovale, P. ovale, P. vivax).