Microbiome Derived Metabolism and Pharmacokinetics

NCT05065671 | Completed Phase 1 FDA Drug

• 1 other identifier: Pro2021000945
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will perform single-dose pharmacokinetic (PK) studies in humans following administration of drugs with known microbiome derived metabolism (MDM) in parallel with preclinical studies. By directly comparing laboratory measurements to clinical results, the investigators will be able to confirm the relevance of MDM in vivo, create microbiome-dependent PK profiles of the MDM positive drugs, and establish methodology to capture the contribution of MDM to inter-individual variability in clinical drug PK profiles.

Conditions

Microbial Colonization

Outcome Measures

Primary Outcomes (6)

• Drug area under the plasma concentration versus time curve (AUC)

  We will calculate the plasma area under the curve for the microbiome derived metabolism positive probe drugs

  After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)

• Drug peak plasma concentration

  We will measure the peak plasma concentration for microbiome derived metabolism positive probe drugs

  After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)

• Drug trough plasma concentrations

  We will measure the trough plasma concentration for microbiome derived metabolism positive probe drugs

  After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)

• Drug volume of distribution

  We will calculate the volume of distribution for microbiome derived metabolism positive probe drugs

  After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)

• Drug half-life

  We will calculate drug half-life for microbiome derived metabolism positive probe drugs

  After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)

• Drug plasma clearance

  We will calculate drug plasma clearance for each microbiome derived metabolism positive drug.

  After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)

Other Outcomes (2)

• Quantitation of microbiome derived metabolism positive drug metabolites in urine

  After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)

• Quantitation of microbiome derived metabolism positive drugs in urine

  After a single dose of a microbiome derived metabolism positive drug (over an 8 hour period for each drug)

Study Arms (2)

Tolcapone

EXPERIMENTAL

Tolcapone 100 mg by mouth once

Drug: Tolcapone 100 MG

Duloxetine

EXPERIMENTAL

Duloxetine 20 mg by mouth once

Drug: Duloxetine 20 MG

Interventions

Tolcapone 100 MG DRUG

Tolcapone 100 mg by mouth once

Tolcapone

Duloxetine 20 MG DRUG

Duloxetine 20 mg by mouth once

Duloxetine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 65 years of age
• Body mass index between 18.5 - 29.9 kg/m2

You may not qualify if:

• Estimated creatinine clearance \< 50 mL/min
• Liver impairment (liver enzymes \> 2 times upper limit)
• Antibiotics in the past 3 months
• History of gastrointestinal disease
• History of autoimmune disorder
• Chronic viral infection
• Smoker
• Alcohol intake (defined as having up to 1 drink per day for women and up to 2 drinks per day for men)
• Use of immune modulating medications
• Diabetes mellitus
• Any history or contraindication to the study medications

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead

Study Sites (1)

Robert Wood Johnson University Hospital Somerset

Somerville, New Jersey, 08876, United States

Location

MeSH Terms

Conditions

Communicable Diseases

Interventions

Tolcapone; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitrophenols; Phenols; Ketones; Nitro Compounds; Thiophenes; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: October 4, 2021
• Study Start: February 1, 2022
• Primary Completion: September 23, 2025
• Study Completion: September 23, 2025
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)