Clinical trial NCT02223871
Conditions: Healthy Subjects
Keywords: Malaria ACT-451840
Sponsor: Idorsia Pharmaceuticals Ltd.
Start date: 2014-06-01; Completion date: 2014-07-01
Enrollment: 8 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This was a single-center study using induced blood stage malaria infection to characterize the activity of ACT-451840 against early Plasmodium falciparum blood stage infection

Detailed description:
The primary objective of the study was to characterize the activity of ACT-451840 administered orally on clearance of Plasmodium falciparum blood stage parasites from the blood in healthy subjects .The inoculum used for blood stage Plasmodium falciparum challenge (BSPC) contained an estimated 1,800 viable parasite-infected erythrocytes diluted into 2 mL of normal saline for injection. Blood was collected for malaria parasitemia assessment by polymerase chain reaction (PCR). Parasitemia ≥ 1,000 parasites/mL indicated that the subjects should be treated with ACT-451840 . If PCR counts were \> 5,000 parasites/mL and symptomatic they were dosed within 24 hours. Subsequent PCR blood sampling were performed prior to ACT-451840 dosing and at 2, 4, 8, 12, 16, 20, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144 hours post-dosing and then approximately times per week until 2 consecutive negative samples, until Riamet® rescue treatment and at the final visit.

Arms: arm 1: All the participants were infected with Plasmodium falciparum parasites (malaria) using malaria-infected human erythrocytes. When the parasitemia reached 1000 counts/mL, all the participants received 500 mg of ACT-451840 as a single oral dose. Compulsory commencement of treatment with Riamet® (artemether-lumefantrine) to ensure complete clearance of any gametocytes, occurred 16 days after ACT-451840 administration (or earlier if required) for all participants. Primaquine was to be administered as a single dose only in participants for whom gametocytes were still identified after administration of Riamet® rescue medication
Interventions: intervention 1: ACT-451840: intervention 2: Plasmodium falciparum-infected human erythrocytes: intervention 3: Artemether 20 mg and lumefantrine 120mg combination tablet: intervention 4: Primaquine:
Intervention descriptions: intervention 1: ACT-451840 500 mg was provided in 100 mL amber glass bottles formulated as a powder for oral suspension. The ACT-451840 suspension was prepared extemporaneously by addition of 25 mL of water and administered orally under fed condition. intervention 2: Each participant was inoculated on Day 0 with approximately 1,800 viable Plasmodium falciparum-infected human erythrocytes administered intravenously. intervention 3: Rescue treatment to ensure clearance of Plasmodium falciparum comprising six doses of four tablets (total course of 24 tablets) given over a period of 60 hours. Each dose of tablets administered orally was immediately followed by food or drinks rich in fat (e.g., milk). intervention 4: Rescue treatment to ensure clearance of Plasmodium falciparum, to be taken as a single oral 45 mg dose with food only if gametocytes were identified after administration of Riamet® rescue medication.

Protocol documents: