Study to Evaluate HT-6184 in Healthy Subjects
Condition: Normal Healthy Subjects
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objectives of this study are to evaluate the safety and tolerability of HT-6184
      when administered as single oral doses at escalating dose levels in healthy volunteer
      subjects.

      The secondary objectives of this study are to characterize the pharmacokinetics (PK) and
      pharmacodynamics (PD) of HT-6184. Results of the PD analyses will be used to determine the
      minimal biologically effective dose (MBED): the lowest dose that achieves >70% target
      inhibition compared to unstimulated vehicle controls over 24 hours in 4 of 6 treated
      volunteers.
    

Detailed description: 
      This is a phase 1, randomized, placebo-controlled, single-center, single and multiple
      ascending dose study designed to evaluate the safety, tolerability, PK, and PD of HT-6184.

      Each cohort in the study will be comprised of 8 subjects, 6 subjects will receive HT-6184 and
      2 subjects will receive placebo. A dose range of 1 mg - 4 mg HT-6184 will be explored in the
      SAD and MAD escalation cohorts in adult healthy volunteer subjects. Safety and PK data from
      the 8 completed cohorts will be reviewed.

      For the SAD portion subjects will be divided into 4 cohorts of 8 subjects in each cohort.
      Four (4) ascending single doses (1 dose level per cohort) will be investigated.

      Subjects will be screened for eligibility to participate in the study up to 26 days (Day -28)
      prior to admission to the study center on Day -2. Eligible subjects will be admitted to the
      study center on Day -2 and will be discharged on Day 2 after all scheduled assessments have
      been completed. Following discharge, subjects will return to the study center for follow-up
      visits on Day 7 and receive a follow-up phone call on Day 30.

      A modified Fibonacci escalation schedule starting at 1 mg, (escalating by 100%) 2 mg,
      (escalating by 50%) 3 mg, and (escalating by 33%) 4 mg. The study will have an ongoing
      assessment of all available safety, tolerability, and concentration data prior to initiation
      of the next cohort.

      For the MAD portion subjects will be divided into 4 cohorts of 8 subjects in each cohort.
      Four (4) ascending multiple doses (1 dose level per cohort) will be investigated.

      Subjects will be screened for eligibility to participate in the study up to 26 days (Day -28)
      prior to admission to the study center on Day -2. Eligible subjects will be admitted to the
      study center on Day -2 and will be discharged on Day 13 after all scheduled assessments have
      been completed. Following discharge, subjects will return to the study center for a follow-up
      visit on Day 21 and receive a follow-up phone call on Day 42.
    

Intervention name(s): HT-6184; HT-6184 Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral capsule; Oral capsule
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: SAD portion in 4 cohorts, with 8 subjects in each cohort, 4 ascending single doses, MAD portion in 4 cohorts, with 8 subjects in each cohort, 4 multiple ascending doses.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment