Drug-Drug Interaction Study of Voriconazole With Clarithromycin.

NCT05380245 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: Dir/A&R/AWKUM/2018/1408-25AWKUM-16002974
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The current study evaluated the Pharmacokinetic (PK) drug-drug interaction (PK-DDI) of voriconazole with clarithromycin in healthy male volunteers. The drug interaction study was designed as a single oral dose, open-label, crossover, and randomized trial. In the first phase of the study, the principal investigator developed a high-performance-liquid chromatography (HPLC) method and validation according to standard ICH guidelines for the quantification of voriconazole in the biological matrix. During the second step, Enrolled volunteers were divided randomly into group A and group B by the "permuted block randomization" technique. Then, voriconazole either alone (2 x 200mg, tab, P/O) or in combination with clarithromycin (Voriconazole 2 x 200mg, tab + clarithromycin 500mg, tab, P/O) was administered to enrolled volunteers in two sequences. Finally, sample collection was carried out and blood samples were collected at specified time periods (i.e., 0.0 (pre-dose), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, and 24 hours) in EDTA or heparinized tubes from the enrolled human volunteers. Further processing of the sample was done for extractions and subsequent analysis with the developed analytical method.

Conditions

Healthy

Keywords

Voriconazole (Voriz); Clarithromycin (CLRM); Washout period; Randomized; Pharmacokinetic drug-drug interaction (PK-DDI); Clinical significance

Outcome Measures

Primary Outcomes (2)

• Plasma Concentration of voriconazole

  Determine the Plasma Concentration particularly the Maximum Plasma Concentration (Cmax) of voriconazole either alone or co-administration with clarithromycin.

  At "Day 1" Pre-dose, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour post-dose and At "Day 16" Pre-dose, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour post-dose.

• Area under the Plasma Concentration versus Time Curve (AUC) of voriconazole

  Determine the Area under the Plasma Concentration versus Time Curve (AUC) of voriconazole either alone or co-administration with clarithromycin.

  At "Day 1" Pre-dose, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour post-dose and At "Day 16" Pre-dose, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour post-dose.

Secondary Outcomes (1)

• Maximum Time to Reach (Cmax) of voriconazole (Tmax)

  At "Day 1" Pre-dose, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour post-dose and At "Day 16" Pre-dose, 0.5hour, 1hour, 1.5hour, 2hour, 3hour, 4hour, 6hour, 8hour, 12hour, 24hour post-dose.

Study Arms (2)

Treatment Voriconazole (alone), then Voriconazole + Clarithromycin.

EXPERIMENTAL

On Day-1, Group-A participants first received Voriconazole (alone) (Dose: 400mg, Dosage form: Tablet, Frequency: Once (OD), Duration of administration: Single Dose, Kind of administration: Oral). After a washout period of two weeks. Then, on Day-16 they received Voriconazole (Dose: 400mg, Dosage form: Tablet, Frequency: Once (OD), Duration of administration: Single Dose, Kind of administration: Oral) along with Clarithromycin (Name of medication of Intervention Formulation: Tablet Klaricid, Dose: 500mg, Dosage form: Tablet, Frequency: Once (OD), Duration of administration: Single Dose, Kind of administration: Oral).

Drug: Voriconazole 200 mg x 2 Tablets; Drug: Clarithromycin 500 mg x 1Tablets

Treatment Voriconazole + Clarithromycin, then Voriconazole (alone).

EXPERIMENTAL

On Day-1, Group-B participants first received Voriconazole (Dose: 400mg, Dosage form: Tablet, Frequency: Once (OD), Duration of administration: Single Dose, Kind of administration: Oral) along with Clarithromycin (Name of medication of Intervention Formulation: Tablet Klaricid, Dose: 500mg, Dosage form: Tablet, Frequency: Once (OD), Duration of administration: Single Dose, Kind of administration: Oral).After a washout period of two weeks. Then, on Day-16 they received Voriconazole (alone) (Dose: 400mg, Dosage form: Tablet, Frequency: Once (OD), Duration of administration: Single Dose, Kind of administration: Oral).

Drug: Voriconazole 200 mg x 2 Tablets; Drug: Clarithromycin 500 mg x 1Tablets

Interventions

Voriconazole 200 mg x 2 Tablets DRUG

Name of medication of Reference Formulation: Tablets Voriconazole Vfend®, 200 mg by Pfizer, Inc. (USA), (Batch No: 00005505; Mfg. date 09/2016).

Also known as: Vfend®

Treatment Voriconazole (alone), then Voriconazole + Clarithromycin.; Treatment Voriconazole + Clarithromycin, then Voriconazole (alone).

Clarithromycin 500 mg x 1Tablets DRUG

Name of medication of Intervention Formulation: Tablet Klaricid, 500 mg by Abbott, Lab Pvt. Ltd. (Karachi, Pakistan), Batch No: 81573XU; Mfg. date 10/2017.

Also known as: klaricid®

Treatment Voriconazole (alone), then Voriconazole + Clarithromycin.; Treatment Voriconazole + Clarithromycin, then Voriconazole (alone).

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male Pakistani volunteers in good health aged 18-35 years were enrolled as participants in this study.
• The selection was based on:
• A complete detailed medical history,
• Clinical examination,
• Voriconazole hypersensitivity test,
• Evaluation of various biochemical tests like Blood Glucose Level, Hemoglobin (Hb) Level, Serum Glutamic-Pyruvic Transaminase (SGPT) Or Alanine Amino Transferase and Aspartate (ALT and AST, respectively) Level, Urine Test, Albumin to Creatinine Ratio (ACR) Test, Glomerular Filtration Rate (GFR) Level, etc.

You may not qualify if:

• Those volunteers were having a history of voriconazole hypersensitivity reaction were excluded from the study.
• Deviation from normal values in the biochemical test report was excluded from the study.
• Having any pathology like chronic renal disease, and hepatic impairment was excluded from the study.
• Having any cardiovascular, gastrointestinal tract, and hematopoietic disorders were excluded from the study.
• Alcohol addicted, smokers and volunteers who cannot sign the permission consent form were excluded from the study.

Sponsors & Collaborators

• Abdul Wali Khan University Mardan: lead

Study Sites (1)

Medical Dispensary, Abdul Wali Khan University Mardan, Pakistan.

Mardan, KPK, 25000, Pakistan

Location

Related Publications (1)

• Mushtaq M, Fatima K, Ahmad A, Mohamed Ibrahim O, Faheem M, Shah Y. Pharmacokinetic interaction of voriconazole and clarithromycin in Pakistani healthy male volunteers: a single dose, randomized, crossover, open-label study. Front Pharmacol. 2023 Jun 9;14:1134803. doi: 10.3389/fphar.2023.1134803. eCollection 2023.

  PMID: 37361220 DERIVED

MeSH Terms

Interventions

Voriconazole; Clarithromycin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Dr. Mehwish Mushtaq, MPhil

  Abdul Wali Khan University Mardan (AWKUM), Pakistan / Metrics Research Organization CRO, Pakistan.

  PRINCIPAL INVESTIGATOR

• Dr. Yasar Shah, Ph.D.

  Abdul Wali Khan University Mardan (AWKUM), Pakistan.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: A single dose, randomized, crossover, open-labeled and two sequence study with a two-week washout period, evaluated the impact of clarithromycin on the pharmacokinetics (PK) profile of voriconazole Pakistani healthy male volunteers.

Study Record Dates

• First Submitted: April 3, 2022
• First Posted: May 18, 2022
• Study Start: November 1, 2018
• Primary Completion: November 16, 2018
• Study Completion: November 30, 2018
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)