| Eligibility |
Inclusion Criteria:
1. Age = 18 to = 64 years.
2. Able and willing to voluntarily complete the informed consent process.
3. Available for and agree to all study procedures, including feces, urine, and blood
collection and adherence to diet control, inpatient monitoring, follow-up visits, and
compliance with all study procedures.
4. Male subjects who are sexually abstinent or surgically sterilized (vasectomy), or
those who are sexually active with a female partner(s) and agree to use an acceptable
method of contraception (such as a condom with spermicide) combined with an acceptable
method of contraception for their non-pregnant female partner(s) (as defined in
Inclusion Criterion # 5) after informed consent, throughout the study, and for a
minimum of 3 months after the last dose of IMP, and who do not intend to donate sperm
in the period from Screening until 3 months following administration of the IMP.
5. Female subjects who meet 1 of the following:
1. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
(human chorionic gonadotropin) at Screening and a negative urine pregnancy test
at baseline prior to the start of IMP and must agree to use acceptable method(s)
of contraception, combined with an acceptable method of contraception for their
male partner(s) (as defined in Inclusion Criterion # 4) after informed consent,
throughout the study and for a minimum of 3 months after the last dose of IMP.
Acceptable methods of contraception include hormonal contraception, hormonal or
non-hormonal intrauterine device, bilateral tubal occlusion, complete abstinence,
and/or vasectomized partner with documented azoospermia 3 months after procedure.
2. WOCBP must not be breastfeeding.
3. Premenopausal women with at least 1 of the following:
i. Documented hysterectomy ii. Documented bilateral salpingectomy iii. Documented
bilateral oophorectomy iv. Documented tubal ligation/occlusion v. Sexual abstinence is
preferred or usual lifestyle of the subject d. Postmenopausal women (12 months or more
amenorrhea verified by follicle- stimulating hormone [FSH] assessment and over 45
years of age in the absence of other biological or physiological causes).
Exclusion Criteria:
1. Acute or chronic medical, surgical, psychiatric, or social condition or laboratory
abnormality that may increase subject risk associated with study participation,
compromise adherence to study procedures and requirements, or may confound
interpretation of study safety or PD results and, in the judgment of the Investigator,
would make the subject inappropriate for enrollment.
2. Body mass index < 18.5 or = 35 kg/m2.
3. History of or current immunodeficiency disorder including human immunodeficiency virus
(HIV) antibody positivity.
4. Hepatitis B surface antigen positivity (subjects with hepatitis B surface antibody
positivity and hepatitis B core antibody positivity are not excluded, provided that
the hepatitis B surface antigen is negative).
5. Hepatitis C antibody positivity, unless a hepatitis C virus ribonucleic acid test is
performed, and the result is negative.
6. History of febrile illness, confirmed bacteremia, or other active infection deemed
clinically significant by the Investigator within 30 days prior to the anticipated
first dose of IMP.
7. History of (within the past month) passage of 3 or more loose stools per day, where
"loose stool" is defined as a Type 6 or Type 7 on the Bristol Stool Chart (see
Appendix 1).
8. Inflammatory or irritable bowel disorder of any grade experienced within the previous
60 days.
9. Active or past history of GI bleeding within 60 days prior to the Screening Visit as
confirmed by hospitalization-related event(s) or medical history of hematemesis or
hematochezia.
10. Underlying cardiovascular disease or uncontrolled gastroesophageal reflux disease
11. Intolerance of or allergic reaction to EcN, esomeprazole and all other PPIs, or any of
the ingredients in SYNB1353 or placebo formulations.
12. Allergy or intolerance to multiple antibiotics which would preclude use of antibiotics
for eradication of SYNB1353 in case of colonization.
13. Currently taking or plans to take Methotrexate, Azuridine, Nitrous Oxide, Phenytoin,
or Carbamazepine.
14. Currently taking or plans to take any type of systemic (e.g., oral or intravenous)
antibiotic within 28 days prior to the first anticipated dose of IMP through final
assessment, including planned surgery, hospitalizations, dental procedures, or
interventional studies that are expected to require antibiotics. Exception: topical
antibiotics are allowed.
15. Major surgery (an operation upon an organ within the cranium, chest, abdomen, or
pelvic cavity) or inpatient hospital stay within the past 3 months prior to Screening.
16. Dependence on alcohol or drugs of abuse.
17. Administration or ingestion of an investigational drug within 30 days or 5 half-lives,
whichever is longer, prior to the Screening Visit, or current enrollment in an
investigational study.
18. Screening laboratory parameters (e.g., chemistry panel, hematology, coagulation) and
ECG outside of the normal limits based on standard ranges or as judged to be
clinically significant by the Investigator. A single repeat evaluation is acceptable.
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