A Phase I/Ib Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of DSM265 in Healthy Subjects and to Assess the Antimalarial Activity of DSM265 in Healthy Subjects with an Induced Blood Stage Plasmodium falciparum Infection.

INTERVENTION: This is essentially a single centre, double‐blind, randomised, placebo‐controlled, ascending dose study in healthy subjects. This study is divided into three parts. The third part defines the pharmacokinetics, safety and tolerability following multiple oral dosing of DSM265. Three cohorts consisting of 8 subjects each, will be enrolled in this part. This stage will begin after the completion of the last single‐dose cohort. A suitable starting dose for Part 3 will be determined from the results of the analysis of drug levels in the blood of subjects from Part 1. Doses for Part 3 of the study will be selected to cover the predicted exposure that was effective in the pre‐clinical studies. Cohort B1: 6 subjects will receive x mg DSM265, 2 subjects placebo; Cohort B2: 6 subjects will receive xx mg DSM265, 2 subjects placebo; Cohort B3: 6 subjects will receive xxx mg DSM265, 2 subjects placebo. Participants will be admitted to the study unit and will stay in the unit for the 5 days for drug administration and post dose follow up assessments. The mode of administration is an oral suspension of DSM265, administered as a single daily dose for 3 consecutive days. Participants in each cohort will receive the same dose on each day. CONDITION: Malaria PRIMARY OUTCOME: The purpose of the study is to determine the maximum oral dose of DSM265 that can be tolerated by healthy adults. SECONDARY OUTCOME: Nil INCLUSION CRITERIA: 1. Written informed consent must be obtained before any assessment is performed. 2. Healthy male and female (of non‐childbearing potential) subjects age 18 to 55 years, in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. a. Women are considered post‐menopausal and not of child bearing potential if they have had at least 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels at the local laboratory levels for post‐menopause; or have had surgical bilateral oophorectomy or bilateral salpingectomy (with or without hysterectomy) at least six months ago. Women on oral contraceptives are to be excluded from the study, also women who have had a tubal ligation. 3. At screening and baseline, vital signs (systolic and diastolic blood