Effects of Isotretinoin on CYP2D6 Activity

NCT03076021 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: STUDY00002324R01GM124264
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Specific Aim: To investigate if isotretinoin (13-cis-retinoic acid) administration decreases CYP2D6 activity in adolescent patients.

Conditions

CYP2D6 Polymorphism

Outcome Measures

Primary Outcomes (1)

• CYP2D6 Activity as Measured by the Molar Concentration Ratio of Dextromethorphan (DM)/Dextrophan (DX)

  dextromethorphan (DM)/dextrophan (DX) molar concentration Metabolic Ratio. The metabolic ratio is unit-less as the molar concentrations cancel out.

  1 week to 6 months

Study Arms (1)

Adolescents

OTHER

dextromethorphan pre- and post isotretinoin

Drug: Isotretinoin; Drug: dextromethorphan

Interventions

Isotretinoin DRUG

Drug interaction study

Also known as: accutane

Adolescents

dextromethorphan DRUG

Drug interaction study

Also known as: robitussin pediatric

Adolescents

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-pregnant
• ≥ 12 years
• Patients with severe acne that are expected to receive isotretinoin for therapeutic reasons

You may not qualify if:

• Weight \< 80 lbs
• Allergy or adverse reaction to dextromethorphan, vitamin A or isotretinoin
• Pregnant or planning to become pregnant
• Unable to follow isotretinoin risk evaluation and mitigation strategies (REMS) program (also known as iPLEDGE program)
• Chronic or persistent cough accompanying asthma, smoking or chronic obstructive pulmonary disease,
• Productive cough,
• Fever,
• Known kidney disease,
• Known liver disease,
• Diabetes
• Obesity, body mass index ≥ 30 kg/m2
• Bipolar disease,
• Attention deficit disorder,
• Social phobia,
• Concurrent or use within 14 days of drugs known to interact with dextromethorphan or cytochrome P450 2D6 (CYP2D6) or drugs known to increase the risk of adverse effects from dextromethorphan

Sponsors & Collaborators

• University of Washington: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Zhao Y, Vary JC Jr, Yadav AS, Czuba LC, Shum S, LaFrance J, Huang W, Isoherranen N, Hebert MF. Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne. Br J Clin Pharmacol. 2024 Mar;90(3):759-768. doi: 10.1111/bcp.15938. Epub 2023 Nov 21.

  PMID: 37864393 RESULT

MeSH Terms

Interventions

Isotretinoin; Dextromethorphan

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Mary Hebert
• Organization: University of Washington

mhebert@u.washington.edu

206-616-5016

Study Officials

• Mary F Hebert, PharmD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pharmacy, Adjunct Professor of Obstetrics and Gynecology

Model Details: Prospective, pre-post drug interaction study evaluating an approved drug (Phase 4) with a Phase 1 study design.

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 9, 2017
• Study Start: July 26, 2016
• Primary Completion: November 27, 2023
• Study Completion: November 27, 2023
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)