Evaluation of Metabolic Markers for the Prediction of DDI of Various CYP3A Substrates and Inhibitors

NCT02975037 | Completed Phase 1 DMC

• 1 other identifier: CYP3A_DDI
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation and validation of metabolic markers for the prediction of drug-drug interaction of various CYP3A4 substrates (sildenafil) and inhibitors (erythromycin/itraconazole) in healthy male subjects

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Quantification of endogenous metabolites (plasma)

  Metabolomic profiles to predict CYP3A activity

  day 1 0h, day 3 0h, day 5 0h

• Quantification of endogenous metabolites (urine)

  Metabolomic profiles to predict CYP3A activity

  day -1 12h~day 1 0h, day 1 0h~12h, day 3 0h~12h, day 4 12h~ day 5 0h, day 5 0h~12h

Secondary Outcomes (2)

• Peak plasma concentration (Cmax)

  day 1 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 3 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 5 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h

• Area under the plasma concentration versus time curve (AUC)

  day 1 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 3 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 5 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h

Other Outcomes (1)

• Quantification of mRNA (whole blood)

  day -1 12h, day 1 0, 12h, day 3 0, 12h, day 4 12h, day 5 0, 12h

Study Arms (2)

sildenafil+clarithromycin

EXPERIMENTAL

Sildenafil 25 mg PO (single dose); Clarithromycin 250 mg PO (3 doses); Sildenafil 25 mg PO + Clarithromycin 250 mg PO (single dose)

Drug: Sildenafil; Drug: Clarithromycin

sildenafil+itraconazole

EXPERIMENTAL

Sildenafil 25 mg PO (single dose); Itraconazole 100 mg PO (3 doses); Sildenafil 25 mg PO + Itraconazole 100 mg PO (single dose)

Drug: Sildenafil; Drug: Itraconazole

Interventions

Sildenafil DRUG

sildenafil 25 mg PO

Also known as: VIAGRA TAB, Pfizer Pharmaceuticals Korea Limited, Korea

sildenafil+clarithromycin; sildenafil+itraconazole

Clarithromycin DRUG

clarithromycin 250 mg PO

Also known as: CLARI TAB, Hanmi Pharm.Co.,Ltd., Korea

sildenafil+clarithromycin

Itraconazole DRUG

itraconazole 100 mg PO

Also known as: ITRA TAB, Hanmi Pharm.Co.,Ltd., Korea

sildenafil+itraconazole

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: Between 19 to 50 years of age, inclusive
• Weight: within 17-28 of Body Mass Index (BMI)
• Subject who are reliable and willing to make themselves available during the study period.
• Subject who are willing to follow the study protocol, and give their written informed consent voluntarily.

You may not qualify if:

• History of hypersensitive reaction to medication (midazolam, itraconazole, rifampicin)
• History of significant clinical illness needs medical caution, including cardiovascular, immunologic, hematologic, neuropsychiatric, respiratory, gastrointestinal, hepatic, or renal disease or other chronic disease
• History or evidence of drug abuse
• Use any prescriptive medication, Korean traditional medication not considered acceptable by the clinical investigator during the last 14 days period before first dosing, or use any medication not considered acceptable by the clinical investigator during the last 7 days period before first dosing (if used medication is considered acceptable by investigator, patients can be included)
• Participation in clinical trials of any drug within 3 months prior to the participation of the study
• Judged to be inappropriate for the study by the investigator

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, South Korea

Location

MeSH Terms

Interventions

Sildenafil Citrate; Clarithromycin; Itraconazole

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Erythromycin; Macrolides; Polyketides; Lactones; Triazoles; Azoles

Study Officials

• Joo-Youn Cho

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: November 29, 2016
• Study Start: February 6, 2017
• Primary Completion: March 4, 2017
• Study Completion: June 23, 2017
• Last Updated: October 27, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)