First-in-Human Study of an Oral Plasmodium Falciparum Plasma Membrane Protein Inhibitor
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): SJ733; Cobicistat
Intervention type(s): Drug; Drug
Intervention description(s): 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.; Commercially available cobicistat 150 mg tablets will be used. It will be administered as a single oral dose together with SJ733.
Other intervention name(s): (+)-SJ000557733; Tybost®
Intervention MeSH terms: Cobicistat
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Antimalarial; First-in-Human; Pharmacokinetic