Enteritis Caused by Radiation Clinical Trial
Official title:
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Orally Administered SYN 020 Delayed Release Capsules in Healthy Subjects
This is a Phase 1, randomized, double-blind, placebo-controlled, multiple-ascending-dose study to assess the PK, safety, and tolerability of SYN-020 oral delayed release capsules (SYN 020) in healthy adults. At least 1 exploratory PD endpoint will also be assessed.
Randomization to treatment will be stratified by sex, with equal numbers of males and females receiving each treatment in each cohort. Up to 5 ascending-dose cohorts of 8 subjects each will be enrolled, and all cohorts will be conducted as planned or until the safety data do not support further escalation. SYN-020 (or placebo) will be administered every 12 hours for 14 consecutive days at escalating doses of 5, 15, 45, and 75 mg in Cohorts 1 through 4, and at a dose not to exceed 75 mg in Cohort 5. Subjects will be screened within 28 days before admission to the clinical research unit (CRU). For each cohort, eligible subjects will be admitted to the CRU on Day -1, and subjects who remain eligible will receive the first dose of study drug in the morning (AM) of Day 1. Subjects will receive study drug every 12 hours for 14 consecutive days. No restriction in food or fluids is required around dosing for any dose other than the AM dose on Days 1 and 14. Subjects will also fast overnight before blood samples are collected for clinical laboratory and/or PD tests on Days 2, 6, 8, 10, 14, and at the follow-up visit on Day 35. A standard Western diet appropriate for a Phase 1 study will be provided at approximately the same times each day during confinement, with each cohort receiving the same meals. Subjects will be discharged from the CRU after the End of Study (EOS) procedures are completed in the AM on Day 15 and will return to the CRU for a follow-up visit on Day 35. For PK assessment, blood samples (primarily on Days 1 and 14) and feces (pre-dose and over selected 48 hour time intervals) will be collected for analysis of SYN 020 concentrations. For PD assessment, blood will be collected and analyzed (or stored for future analysis) for at least 1 of the exploratory endpoints. Fecal samples for PD assessment will be taken from the feces collected for PK assessment. These investigations will explore potential biomarkers for future SYN 020 indications and will be strictly and directly related to the pharmacology of SYN 020. While gastrointestinal microbiome/metabolome analyses include genotyping of the gut bacteria, no human genotyping will be performed. Safety and tolerability will be monitored throughout the study. Safety assessments will include clinical laboratory tests, vital signs, 12-lead ECGs, physical examinations, monitoring for AEs, and ADA testing. Adverse event data will be collected from the time of informed consent through the follow-up visit at Day 35 or until the AE resolves or becomes stable. ;