Ultralow Dose PAH Binary Mixture Study

NCT03631667 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: LPI-8554R01ES028600
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation of the pharmacokinetics for \[14C\]-benzo\[a\]pyrene (\[14C\]-BaP) and metabolites in plasma and urine over 48 hours following a 50 ng dose (5.4 nCi) alone or with 1250 ng phenanthrene.

Conditions

Environmental Exposure

Keywords

Benzo[a]pyrene; Accelerator Mass Spectrometry; Polycyclic Aromatic Hydrocarbons; Phenanthrene

Outcome Measures

Primary Outcomes (2)

• Peak Plasma Concentration of 14C-BaP Cmax

  Determination of highest concentration of 14C-BaP in plasma. Blood samples collected at 0 (baseline), 0.25, 0.5, 1, 2, 3, 4, 8, 24, and 48 hour after dosing. All time points were used to determine Cmax.

  0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles

• Time at Highest Plasma Concentration of 14C-BaP Tmax

  Determination of time at which plasma concentration of 14C-BaP is highest. Blood samples collected at 0 (baseline), 0.25, 0.5, 1, 2, 3, 4, 8, 24, and 48 hour after dosing. All time points were used to determine Tmax.

  0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles

Secondary Outcomes (2)

• Area Under Plasma Concentration of 14C-BaP Versus Time Curve AUC

  0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles

• Rate of Elimination of 14C-BaP (Half Life)

  0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles

Study Arms (1)

50 ng dose and 50 ng dose plus 1250 ng phenanthrene

EXPERIMENTAL

Cycle 1: Capsule containing 50 ng (5.4 nCi) \[14C\]-benzo\[a\]pyrene (BaP). Cycle 2: Capsule containing 50 ng (5.4 nCi) \[14C\]-benzo\[a\]pyrene (BaP) and 1250 phenanthrene. At least 3 weeks will pass between cycles as a washout period.

Drug: [14C]-benzo[a]pyrene; Drug: [14C]-benzo[a]pyrene plus phenanthrene

Interventions

[14C]-benzo[a]pyrene DRUG

Oral micro-dose (50 ng) (5.4 nCi)

Also known as: Carcinogenic PAH environmental pollutant

50 ng dose and 50 ng dose plus 1250 ng phenanthrene

[14C]-benzo[a]pyrene plus phenanthrene DRUG

Oral micro-dose of 50 ng (5.4 nCi) \[14C\]-benzo\[a\]pyrene plus 1250 ng phenanthrene

Also known as: Binary mixture of carcinogenic PAH and non-carcinogenic PAH

50 ng dose and 50 ng dose plus 1250 ng phenanthrene

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-65 (inclusive)
• If female, must be post-menopausal or have had surgical sterilization to eliminate any possibility for fetal exposure
• Willing to defer blood donation for one month before, throughout, and one month after completion of study activities
• Willing to avoid consuming cruciferous vegetables, I3C or DIM supplements, smoked or cured meat or cheeses, or charcoal-grilled meats for 2 weeks prior to and during each study cycle (gas grilled foods acceptable)

You may not qualify if:

• Smoker (tobacco or other substances) or use of smokeless tobacco in past 3 months or living with smoker
• Regular use of medications that affect gut motility or nutrient absorption (e.g. cholestyramine, sucralfate, orlistat, pro- or anti-motility agents)
• History of gastrointestinal surgery (e.g. bariatric surgery, cholecystectomy) or gastrointestinal disorder (Crohn's disease, celiac disease, IBS, or colitis)
• Current or history of kidney or liver disease
• Occupational PAH exposure (e.g. roofers, asphalt pavers, fire-fighters, etc.)
• Regular use of indole-3-carbinol or DIM dietary supplements

Sponsors & Collaborators

• Oregon State University: lead
• National Institute of Environmental Health Sciences (NIEHS): collaborator
• Lawrence Livermore National Laboratory: collaborator
• Pacific Northwest National Laboratory: collaborator

Study Sites (1)

Oregon State University

Corvallis, Oregon, 97331, United States

Location

MeSH Terms

Interventions

phenanthrene

Results Point of Contact

• Title: David E. Williams, PhD
• Organization: Oregon State University

david.williams@oregonstate.edu

541-737-3277

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Deidentified samples will be analyzed by AMS at Lawrence Livermore National Laboratory and the pharmacokinetics determine at Pacific Northwest National Laboratory.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 15, 2018
• Study Start: October 1, 2018
• Primary Completion: January 1, 2024
• Study Completion: February 1, 2024
• Last Updated: May 22, 2025
• Results First Posted: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)