Trial Targeting Gut Bacterial Androgen Production to Reverse Therapeutic Resistance to Abiraterone in Patients With Metastatic Prostate Cancer

Inclusion Criteria:

* Males aged 18 years of age and above.
* Prostate adenocarcinoma
* Absolute PSA ≥ 2.0 ng/mL at screening.
* PSA (+/- radiographic) progression after having been on abiraterone and prednisone for at least 12 weeks.
* Must be maintained on a GnRH analogue or have undergone orchiectomy.
* Participants must have a life expectancy ≥ 6 months
* Ability to swallow study medication tablets
* Willing to abstain from alcohol during and for 14 days after treatment with metronidazole
* Willing and able to collect urine and stool samples per protocol

Exclusion Criteria:

* Active infection or other medical condition that would make dexamethasone use contraindicated
* Any chronic medical condition requiring a higher systemic dose of corticosteroid
* Pathological finding consistent with small cell carcinoma of the prostate
* Has imminent or established spinal cord compression based on clinical findings and/or MRI.
* Chronic liver disease with Child-Pugh class C cirrhosis (see calculator in protocol)
* Bilirubin \>3x ULN or AST and ALT \>5x ULN
* Congenital prolonged QTc syndrome or QTc \> 500 msec (non-paced rhythm)
* History of pituitary or adrenal dysfunction
* Uncontrolled diabetes (Hemoglobin A1c \> 10%) or increasing doses of insulin within the past 4 weeks due to poorly controlled glucoses.
* Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational drug study
* Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including, but not limited to:

  * Any uncontrolled major infection.
  * Crohn's disease or ulcerative colitis.
  * Known or suspected toxic megacolon and/or known small bowel ileus.
  * Known allergy to any of the compounds under investigation.
* On antibacterial therapy within 30 days prior to administration of study treatment.
* Any condition or situation which, in the opinion of the investigator, would put the subject at risk, or interfere with the subject's participation in this study.