In 3 Phase 2 clinical trials, atovaquone alone, proguanil hydrochloride alone, and the combination of atovaquone and proguanil hydrochloride were evaluated for the treatment of acute, uncomplicated malaria caused by P. falciparum. Among 156 evaluable patients, the parasitological cure rate (elimination of parasitemia with no recurrent parasitemia during follow‑up for 28 days) was 59/89 (66%) with atovaquone alone, 1/17 (6%) with proguanil hydrochloride alone, and 50/50 (100%) with the combination of atovaquone and proguanil hydrochloride.

MALARONE was evaluated for treatment of acute, uncomplicated malaria caused by P. falciparum in 8 Phase 3 randomized, open-label, controlled clinical trials (N = 1,030 enrolled in both treatment groups). The mean age of subjects was 27 years and 16% were children 12 years and younger; 74% of subjects were male. Evaluable patients included those whose outcomes at 28 days were known. Among 471 evaluable patients treated with the equivalent of 4 MALARONE tablets once daily for 3 days, 464 had a sensitive response (elimination of parasitemia with no recurrent parasitemia during follow‑up for 28 days) (Table 8). Seven patients had a response of RI resistance (elimination of parasitemia but with recurrent parasitemia between 7 and 28 days after starting treatment). In these trials, the response to treatment with MALARONE was similar to treatment with the comparator drug in 4 trials.

When these 8 trials were pooled and 2 additional trials evaluating MALARONE alone (without a comparator arm) were added to the analysis, the overall efficacy (elimination of parasitemia with no recurrent parasitemia during follow‑up for 28 days) in 521 evaluable patients was 98.7%.

The efficacy of MALARONE in the treatment of the erythrocytic phase of non-falciparum malaria was assessed in a small number of patients. Of the 23 patients in Thailand infected with P. vivax and treated with atovaquone/proguanil hydrochloride 1,000 mg/400 mg daily for 3 days, parasitemia cleared in 21 (91.3%) at 7 days. Parasite relapse occurred commonly when P. vivax malaria was treated with MALARONE alone. Relapsing malarias including P. vivax and P. ovale require additional treatment to prevent relapse.

The efficacy of MALARONE in treating acute uncomplicated P. falciparum malaria in children weighing ≥5 and <11 kg was examined in an open‑label, randomized trial conducted in Gabon. Patients received either MALARONE (2 or 3 MALARONE pediatric tablets once daily depending upon body weight) for 3 days (n = 100) or amodiaquine (10 mg/kg/day) for 3 days (n = 100). In this study, the MALARONE tablets were crushed and mixed with condensed milk just prior to administration. An adequate clinical response (elimination of parasitemia with no recurrent parasitemia during follow‑up for 28 days) was obtained in 95% (87/92) of the evaluable pediatric patients who received MALARONE and in 53% (41/78) of those evaluable who received amodiaquine. A response of RI resistance (elimination of parasitemia but with recurrent parasitemia between 7 and 28 days after starting treatment) was noted in 3% and 40% of the patients, respectively. Two cases of RIII resistance (rising parasite count despite therapy) were reported in the patients receiving MALARONE. There were 4 cases of RIII in the amodiaquine arm.