Pharmacokinetic Interactions of Metamizole (Dipyrone) in Healthy Subjects

NCT03990129 | Completed Phase 1

• 1 other identifier: 2018-00753
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators conducted a single center, two-phased, open, controlled pharmacokinetic study to investigate the drug-drug interaction potential of metamizole. For this reason, healthy male volunteers were screened. Enrolled participants were phenotyped on day 1 using the Basel Cocktail (phenotyping cocktail containing specific substrates for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4). After, they received metamizole treatment for 8 days (3 grams per day). On the 8th day (day 9), they were phenotyped again with the Basel Cocktail and the respective phenotypes (d1 vs. d9) were compared.

Conditions

Inhibition; Induction; Drug-Drug Interaction

Keywords

Metamizole; Dipyrone; Basel Cocktail; Drug-Drug Interaction; Phenotyping

Outcome Measures

Primary Outcomes (3)

• Effect on AUC ratio between parent and metabolite

  AUC ratio between parent and metabolite of specific cytochrome P450 substrates to determine a shift which may indicate either induction or inhibition of the specific cytochrome P450

  12 hours

• Cmax

  Maximal Concentration in plasma of parent and metabolite

  24 hours

• tmax

  time to reach Cmax

  24 hours

Study Arms (1)

Study population

OTHER

All participants

Drug: Metamizole

Interventions

Metamizole DRUG

One week treatment with metamizole (500 mg tablets, 2-2-2)

Study population

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects aged between 18 and 45 years (inclusive) at screening
• BMI between 18 and 28 kg/m2 (inclusive) and bodyweight at least 50 kg at screening
• systolic blood pressure: 100-140 mmHg, diastolic blood pressure: 60-90 mmHg and heart rate: 45-90 bpm (inclusive), measured on the leading arm, in the supine position at screening
• No clinically significant findings on the physical examination at screening
• Signed informed consent prior to any study-mandated procedure
• Hematology and clinical chemistry results not deviating from the normal range to clinically relevant extent at screening
• Ability to communicate well with the investigator to understand and comply with the requirements of the study

You may not qualify if:

• Smoking \>5 cigarettes per day
• History or clinical evidence of alcoholism or drug abuse within the 3- year period prior to screening
• Loss of ≥250 ml of blood within 3 months prior to screening. Treatment with an investigational drug within 30 days prior to screening
• Previous systemic treatment with any prescribed or over the counter medication (including herbal medicines such as St John's Wort) within 2 weeks prior to the intended start of the study
• Inability to stop consumption inducing food products (e.g. grapefruit juice) 72 h before start of the study
• Excessive caffeine consumption (\>8 cups of coffee/ 8l coca cola per day)
• Legal incapacity or limited legal capacity at screening
• Positive results from urine drug screen at screening
• History or clinical evidence of any disease (e.g. gastrointestinal disease: Morbus Crohn, Colitis Ulcerosa, anamnestic gastrointestinal bleeding) and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk for toxicity
• Known hypersensitivity to Metamizole (Novalgin®) or excipients of the drug formulation
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

Clinical Trial Unit, University Hospital Basel

Basel, Canton of Basel-City, 4053, Switzerland

Location

MeSH Terms

Conditions

Inhibition, Psychological

Interventions

Dipyrone

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Aminopyrine; Pyrazolones; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Stephan Krähenbühl, Prof. Dr. MD

  Head of Clinical Pharmacology, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two phase study, before-after comparison

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 18, 2019
• Study Start: September 4, 2018
• Primary Completion: October 31, 2018
• Study Completion: October 31, 2018
• Last Updated: June 20, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)