A Phase 1, Randomized, Placebo-Controlled, Ascending Cohort, Dose Escalation Study in Normal Healthy Volunteers
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      GSK3179106 is a potent and relatively selective inhibitor of RET kinase which has been
      designed to be a safe and effective therapy for irritable bowel syndrome (IBS) patients .

      This is a randomized, double-blind (sponsor unblind), placebo-controlled, dose escalating,
      four period, single-dose crossover, first time in human study to assess the safety,
      tolerability and pharmacokinetics of GSK3179106 in normal healthy subjects.

      The study will be composed of 2 cohorts, each having screening (21 days prior to first dose
      of study drug), Treatment, and follow-up periods (7-10 days after their last dose [Day 1 of
      dosing period 4]). The Treatment period will include 4 dosing periods. Subjects will
      participate in either Cohort 1 or Cohort 2. The total duration of the study for each subject
      will be approximately 10 weeks. A sufficient number of healthy subjects will be screened to
      enrol 16 subjects who complete the planned study procedures. Each dosing period will be
      staggered so that only 2 of the 8 subjects will be administered study drug initially. Once 24
      hours (h) have elapsed, and provided there are no safety concerns, the remainder of subjects
      scheduled for that dosing period may be dosed. A review of safety and tolerability will occur
      prior to administration of the next dose level. This same procedure will be followed for each
      escalating dosing period. Subjects assigned to Cohort 1 will participate in 1 placebo and 3
      dose escalating periods. Subjects assigned to Cohort 2 will participate in up to 4 dosing
      periods which include up to 2 escalating doses and placebo in Periods 1 and 2, and a pilot
      food effect in Periods 3 and 4. Within each cohort, subjects will return for their next
      scheduled dosing period approximately 14 days after administration of the study drug during
      the prior dosing period. Cohort 2 will proceed after completion of the treatment periods in
      Cohort 1. Each subject will be enrolled in only one cohort. The planned dose range is 10
      milligram (mg) to 200 mg in Cohort 1. The actual doses to be administered may be adjusted
      based on safety, tolerability, and pharmacokinetic data at previous dose levels; these dose
      adjustments may involve either an increase or a decrease in the planned dose for both Cohorts
      1 and 2. There are no formal hypotheses being tested in this study.
    


Intervention name(s): GSK3179106; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): GSK3179106 will be provided as white to slightly colored round or oblong tablet for oral administration with unit dose strength of 5 mg, 25 mg and 100 mg; Placebo will be provided as white to slightly colored round or oblong tablet for oral administration with unit dose strength to match actives across all strengths
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Healthy volunteer; Safety; Pharmacokinetics; Dose escalation; GSK3179106; Rearranged during Transfection; Irritable Bowel Syndrome; Adults