Pharmacokinetics, Safety, and Tolerability of SYN-020
Condition: Enteritis Caused by Radiation (Disorder)
MeSH terms: Enteritis
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1, single-center, open-label, single ascending dose study to assess the PK,
      safety, and tolerability of SYN-020 delayed release capsules administered orally to healthy
      adult male and female subjects with a BMI of 18.5 to 27 kg/m2. Up to 36 subjects will
      participate, in each of up to 6 sequential cohorts. Single doses of 5, 15, 45, and 150 mg
      SYN-020 are planned in Cohorts 1 through 4, respectively. Cohorts 5 and 6, if enrolled, will
      receive doses that were well tolerated in an earlier cohort to determine the effect of BMI
      and/or a high-fat meal on the SYN-020 PK profile.

      For each cohort, eligible subjects will be admitted to the clinic on Day -1, and receive
      study drug in the morning of Day 1. For PK analysis, blood and feces will be collected before
      dosing and for up to 96 hours (blood) or 120 hours (feces) after dosing. Subjects will be
      discharged from the clinic after the End of Study procedures are completed on Day 6.
    

Detailed description: 
      Intestinal alkaline phosphatase (IAP) is a naturally occurring enzyme produced by the small
      intestine in all mammals, including humans, and is considered essential for promoting normal
      gastrointestinal (GI) function and maintaining proper gut homeostasis, as well as appearing
      to play a pivotal role in the mediation of inflammation.

      SYN-020 is a recombinant bovine IAP isotype II being developed by Synthetic Biologics, Inc.
      to reduce the cumulative GI toxicity and inflammation that can be associated with repeat
      administration of radiation in patients with cancer.

      This is a Phase 1, single-center, open-label, single ascending dose study to assess the PK,
      safety, and tolerability of SYN-020 delayed release capsules administered orally to healthy
      adult male and female subjects with a BMI of 18.5 to 27 kg/m2. Up to 36 subjects will
      participate, with 6 subjects (approximately equal numbers of male and females) in each of up
      to 6 sequential cohorts. Single doses of 5, 15, 45, and 150 mg SYN-020 are planned in Cohorts
      1 through 4, respectively. Cohorts 5 and 6, if enrolled, will receive doses that were well
      tolerated in an earlier cohort to determine the effect of BMI and/or a high-fat meal on the
      SYN-020 PK profile, and will be described fully in a protocol amendment.

      For each cohort, eligible subjects will be admitted to the clinical research unit (CRU) on
      Day -1, and subjects who remain eligible will, after a minimum 10-hour overnight fast,
      receive study drug in the morning of Day 1. For PK analysis, blood and feces will be
      collected before dosing and for up to 96 hours (blood) or 120 hours (feces) after dosing.
      Subjects will be discharged from the CRU after the End of Study (EOS) procedures are
      completed on Day 6.
    

Intervention name(s): SYN-020 delayed release capsule
Intervention type(s): Drug
Intervention description(s): SYN-020, is an opaque, white, size 3 HPMC capsule for oral administration containing enteric-coated, delayed-release pellets.
Other intervention name(s): Intestinal Alkaline Phosphatase
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: single ascending dose
Masking: None (Open Label)
Primary purpose: Treatment