NCT02661373

First-in-Human Study of an Oral Plasmodium Falciparum Plasma Membrane Protein Inhibitor

Phase 1a, First-In-Human, Dose-Escalation Study of (+)-SJ000557733 (SJ733), an Oral, Novel Inhibitor of Plasmodium Falciparum Plasma Membrane Protein PfATP4

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 44 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

Malaria is an infectious disease caused by a parasite that is passed to humans when an infected mosquito bites a person. About 3.4 billion people live in areas of the world where malaria is regularly found. In many countries, malaria is one of the leading causes of illness and death. Despite this, there are a limited number of drugs, called antimalarials, that can be used to treat malaria and increasing reports of resistance to existing antimalarials. The purpose of this research study is to test a new experimental antimalarial drug called SJ733 to first assess its safety, tolerability and blood levels in healthy adult volunteers. Single-dose, multi-dose and boosted-dose cohorts (both single and multi-dose) will be studied. The pharmacoenhancer (booster), cobicistat, will be given in combination with SJ733 in the boosted dose-cohorts. PRIMARY OBJECTIVES: * To assess the preliminary safety and tolerability of escalating doses of antimalarial SJ733 in healthy human volunteers. * To investigate the pharmacokinetic (PK) profile of escalating doses of antimalarial SJ733 and its metabolite in healthy human volunteers. * To identify a dose of SJ733 that can be tested in a separate Phase 1b human malaria challenge study. * To assess the preliminary safety and tolerability of SJ733 in healthy adult volunteers after multiple oral dosing. * To assess the pharmacokinetics of SJ733 and its metabolite SJ506 after multiple dosing of SJ733 in healthy adult volunteers. * To assess the preliminary safety and tolerability of escalating single oral doses of SJ733 in combination with cobicistat among healthy adult volunteers. * To assess the pharmacokinetics of SJ733 and its metabolite SJ506 after single oral doses of SJ733 in combination with cobicistat among healthy adult volunteers. * To assess the preliminary safety and tolerability of SJ733 in combination with cobicistat in healthy adult volunteers after multiple oral dosing. * To assess the pharmacokinetics of SJ733 and its metabolite SJ506 after multiple dosing of SJ733 in combination with cobicistat among healthy volunteers. SECONDARY OBJECTIVE: * To assess the impact of food intake on the pharmacokinetic profile of antimalarial SJ733.

Detailed description

This is a single site, Phase 1a, first-in-human, oral, primarily single-dose, dose escalation study of (+)-SJ000557733 (SJ733) in healthy adult volunteers. SJ733, is an investigational oral anti-malarial agent is a novel inhibitor of Plasmodium falciparum plasma membrane protein (PfATP4). Subjects meeting eligibility criteria will be enrolled using a leap frog, fixed dose escalation design with an adaptive component where 6 subjects are enrolled per dose cohort. Following successful completion of the safety and pharmacokinetic (PK) assessment resulting from the single-dose escalation portion of the study, a three-dose cohort study will be undertaken. It includes once per day oral dosing for 3 consecutive days. Both single and multi-dose cohorts of SJ733 in combination with cobicistat (boosted cohorts) will also be completed. After the study results from the single-dose cohorts of SJ733 in combination with cobicistat (boosted cohorts) were reviewed, multi-dose cohorts of SJ733 in combination with cobicistat (boosted cohorts) were not conducted and Phase 2 study planning initiated.

Conditions

• Malaria

Interventions

Type	Name	Description
DRUG	SJ733	SJ733 is an oral, novel inhibitor of Plasmodium Falciparum plasma membrane protein PFATP4. It will be administered as a single, multi, or boosted oral dose.
DRUG	Cobicistat	Commercially available cobicistat 150 mg tablets will be used. It will be administered as a single oral dose together with SJ733.

Timeline

• Start date: 2016-03-01
• Primary completion: 2018-03-09
• Completion: 2018-03-09
• First posted: 2016-01-22
• Last updated: 2019-01-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study