Relation Between Blood Concentration of Colchicine and Response to Colchicine Treatment in Gout Flare

NCT03933007 | Terminated Phase 4

• 2 other identifiers: P170409J2018-002542-37
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Gout, secondary to sodium urate crystal deposition, is responsible of recurrent inflammatory painful flares. Efficacy of colchicine which is the first line drug for the treatment and prophylaxis of gout flare varies and only half of treated patients experience good response. This study aims to optimize colchicine prescription for the treatment and prophylaxis of gout flare. Current data suggest that efficiency of colchicine relies on its maximum blood concentration (Cmax). In this study, the investigators hypothesize that responders to colchicine treatment have higher colchicine Cmax than non-responder patients following the recommended dose regimen (1 mg then 0.5 mg 1 hour later). The individual pharmacokinetics (PK) of colchicine remains poorly investigated while the assessment of individual drug metabolisms can be performed. The hypothesis of this study stands that several factors contribute to the variability of colchicine Cmax. The analysis of individual PK profile and a well-characterized metabolism of colchicine will permit a personalized treatment regimen for the treatment and prophylaxis of gout flares.

Conditions

Gout Flare

Outcome Measures

Primary Outcomes (1)

• Maximum plasma concentration of colchicine

  Maximum plasma concentration of colchicine in responders and non-responders to colchicine treatment for gout flare during pharmacokinetic study performed 1 month after flare resolution and before initiation of urate-lowering therapy.

  From drug administration to 6 hour post-drug administration

Secondary Outcomes (6)

• Maximum Plasma Concentration [Cmax]

  From drug administration to 6 hour post-drug administration

• Time needed to reach Cmax [Tmax ]

  From drug administration to 6 hour post-drug administration

• Absorption rate constant [Ka]

  From drug administration to 6 hour post-drug administration

• Volume of distribution [Vd]

  From drug administration to 6 hour post-drug administration

• Area under the curve [AUC]

  From drug administration to 6 hour post-drug administration

Study Arms (1)

Pharmacokinetic study

OTHER

all participants will undergo pharmacokinetic study and take colchicine (1.5 mg over 1 hour), midazolam (1 mg) and fexofenadine (120 mg)

Drug: Colchicine,; Drug: midazolam,; Drug: fexofenadine

Interventions

Colchicine, DRUG

the day of phenotyping assay * Colchicine : 1.5 mg over 1 hour (1 mg + 0.5 mg 1 hour later)

Pharmacokinetic study

midazolam, DRUG

Midazolam 1 mg

Pharmacokinetic study

fexofenadine DRUG

Fexofenadine 120 mg

Pharmacokinetic study

Eligibility Criteria

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

You may qualify if:

• Patients (\> 18 years old) with gout flare defined by following items :
• Identification of sodium urate crystals in synovial fluid analysis
• Or gout flare diagnosis according to Nijmegen criteria (score \> 8/13)
• Man (2 pts)
• History of flare (2 pts)
• Flare involving first metatarsophalangeal joint (2.5 pts)
• Maximum of flare within 24h (0.5pt),
• Redness (1 pt),
• History of hypertension or cardiovascular diseases (1.5 pts),
• Serum urate level \> 360 µmol/l during flare (3.5 pts)
• Duration of flare \< 48 h
• Monoarticular involvement

You may not qualify if:

• Hypersensitivity to colchicine, fexofenadine, benzodiazepine or the excipients of these drugs
• Contra-indication to colchicine : chronic kidney disease stage 4-5, severe hepatic impairment, treatment by macrolide antibiotics
• Used of pain-killers other than acetaminophen
• Involvement in another clinical trial with drug administration
• Illiteracy
• Pregnant woman or breastfeeding

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Lariboisière-Service de Rhumatolologie

Paris, 75010, France

Location

MeSH Terms

Interventions

Colchicine; Midazolam; fexofenadine

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hang-Korng EA, PhD, MD

  AP-HP - Groupe hospitalier Lariboisière Fernand Widal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: all participants will perform the pharmacokinetic study and take colchicine 1 mg + 0.5 mg 1 hour later, midazolam 1 mg and fexofenadine 120 mg.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: all participants will perform the pharmacokinetic study and take colchicine 1 mg + 0.5 mg 1 hour later, midazolam 1 mg and fexofenadine 120 mg. A pharmacokinetic study is an interventional study with only one arm.

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: May 1, 2019
• Study Start: September 10, 2019
• Primary Completion: October 10, 2019
• Study Completion: February 28, 2024
• Last Updated: June 3, 2024

Record last verified: 2024-05

Locations

FR (1)