Pharmacokinetic Study of Terpinolene in Healthy Subjects (PKT Study)

NCT ID: NCT06691126

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-04
• Study Completion Date: 2024-12-03

Brief Summary

The study aims to check if our prediction about the uptake, distribution, and elimination of terpinolene (a food additive commonly found in e.g. fruits and herbs) from the human body is accurate.

Detailed Description

Traditionally, the toxicological hazards of chemical substances have been identified and evaluated using animal studies. With the global shift towards limiting the use of animals in human safety assessment, "Next Generation Risk Assessment (NGRA)" has been conceptualized as a human-relevant, exposure-led approach integrating in silico, in chemico and in vitro methodologies. Consequently, in silico physiologically based pharmacokinetic (PBPK) modelling strategies have emerged as a central component of the NGRA paradigm. By mapping compound behaviour (i.e. absorption, distribution, metabolism and excretion) in the body to a physiologically realistic compartmental structure comprising various organs connected by the circulating blood system, PBPK models (i) provide the link between in vitro hazard data and human-relevant exposures and (ii) enable conversion of external doses to internal exposures which can then be compared to internal thresholds of toxicological concern (iTTC).

Established methods exist to develop a PBPK model for any chemical based solely on in vitro and in silico parameters. However, assessment of the predictive accuracies of any PBPK model-derived simulations is highly reliant on the availability of in vivo pharmacokinetic (PK) datasets. This inherently limits the widespread applicability of PBPK modelling to the vast chemical space of non-pharmacological entities whereby there is a paucity of in vivo data. To circumvent this limitation, Ellison et al. introduced a read across framework for evaluating the PBPK model of a target chemical (chemical with no PK data) using PK data from an analogous source chemical (chemical with existing PK data).

In this study, the investigator aims to further evaluate and develop this PK read-across approach to consider non-pharmaceutical compounds. A target compound with no human PK data available was identified, which is a food flavouring agent, terpinolene and its source compound, limonene. A PBPK model for terpinolene will be built and used to compare the in vitro absorption, distribution, metabolism and elimination (ADME) parameters between terpinolene and limonene. To further validate this read-across approach, a prospective clinical study to obtain the missing in vivo PK of terpinolene is proposed.

Conditions

Pharmacokinetics of Terpinolene

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Single arm

n=15, single oral dose of 200mg of food-grade terpinolene in 5ml of olive oil

Group Type: EXPERIMENTAL

Terpinolene in olive oil

Intervention Type: OTHER

Single oral dose of 200mg food-grade terpinolene in 5ml of olive oil

Interventions

Terpinolene in olive oil

Single oral dose of 200mg food-grade terpinolene in 5ml of olive oil

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Aged 21-50
• Chinese, Malay and Indian ethnicities
• Male or female
• Adequate fluency in the English language to understand the informed consent process, study instructions and study assessments
• Sufficient vision and hearing to complete the study procedures
• Willing and able to participate and to give written informed consent

Exclusion Criteria

• Past (<3 months prior to the study) or current major metabolic, endocrine, gastrointestinal or cardiovascular disease
• Individuals diagnosed with non-alcoholic fatty liver disease
• Major surgery in the past 2 months
• On chronic medication
• Allergy to olive oil
• Vegetarian/vegan
• Smoking
• Pregnant or lactating
• Alcohol intake >1 units per day
• Body Mass Index <18.5 kg/m2 or ≥27 kg/m2
• Body weight <54 kg
• Member of the study team or their immediate family members

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institute for Human Development and Potential (IHDP), Singapore

OTHER

Sponsor Role: collaborator

Singapore Institute of Food and Biotechnology Innovation

OTHER_GOV

Sponsor Role: lead

Responsible Party

Chun Yip James Chan

Principal Scientist I

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James Chan, PhD

Role: PRINCIPAL_INVESTIGATOR

Singapore Institute of Food and Biotechnology Innovation (SIFBI), A*STAR

Locations

Human Development Research Centre, IHDP, A*STAR

Singapore, , Singapore

Countries

Singapore

Other Identifiers

2024-099

Identifier Type: -

Identifier Source: org_study_id