InhibitionPhase 1NCT03990129
Pharmacokinetic Interactions of Metamizole (Dipyrone) in Healthy Subjects
A Phase 1 study testing Metamizole in people with Inhibition and Induction, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Inhibition, Induction, Drug-Drug Interaction
- What is being tested?
- Metamizole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSwitzerland
- Study dates
- 4 Sep 2018to 31 Oct 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Clinical Trial Unit, University Hospital Basel
Basel, Canton of Basel-City, 4053
About this study
Official title: Single-center, Open, Controlled Study to Investigate the Interaction of Metamizole With the Cytochrome p450 System in Healthy Subjects by Application of the Basel Cocktail
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.
Read the detailed description
12 healthy male subjects meeting the inclusion and exclusion criteria were enrolled. On day 1, they ingested a capsule containing the Basel Cocktail (1A2: caffeine, 2B6: efavirenz, 2C9: flurbiprofen, 2C19: omeprazole, 2D6: metoprolol, 3A4: midazolam) in fastened state. Blood samples were withdrawn over 24 hours and the AUC ratios between metabolite and parent were calculated to determine the phenotype.
Probands began metamizole treatment (3000 mg/day) at the day of the 24h measurement. After 3-4 day, probands were returning to the facility to ensure safety during the metamizole treatment, blood cell count and metamizole metabolites were measured. After the 7 days of treatment, probands were exposed again to the Basel Cocktail in a fastened state. Probands were still exposed to metamizole to ensure potential inhibition. 24 hours plasma samples were withdrawn, area under the curve (AUC) ratios were calculated and compared to the basal state. After an end of study visit on the day of the 24h blood sample (following the second study day), probands were discharged.
- Conditions
- Inhibition, Induction, Drug-Drug Interaction
- Being tested
- Metamizole
- Keywords
- Metamizole, Dipyrone, Basel Cocktail, Drug-Drug Interaction, Phenotyping
- Medical subject headings
- Inhibition, Psychological
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetamizoleDrug
One week treatment with metamizole (500 mg tablets, 2-2-2)
| Study group | Role | What they receive |
|---|---|---|
| Study population | Other | All participants Receives: Drug: Metamizole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 hours
Cmax
Maximal Concentration in plasma of parent and metabolite
Measured: 24 hours
tmax
time to reach Cmax
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2019
- Study start4 Sep 2018
- Primary completion31 Oct 2018
- Study completion31 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InhibitionStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Two phase study, before-after comparison
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephan Krähenbühl, Prof. Dr. MD, Principal investigator, Head of Clinical Pharmacology, University Hospital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03990129
- Sponsor's protocol ID
- 2018-00753
- Other IDs
- 2018
- Status last verified
- Jun 2019
- First submitted
- 14 Jun 2019
- Last updated
- 20 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-center, Open, Controlled Study to Investigate the Interaction of Metamizole With the Cytochrome p450 System in Healthy Subjects by Application of the Basel Cocktail
- ClinicalTrials.gov ID
- NCT03990129
- Acronym / sponsor ID
- 2018-00753
- Conditions
- Inhibition, Induction, Drug-Drug Interaction
- Keywords
- Metamizole, Dipyrone, Basel Cocktail, Drug-Drug Interaction, Phenotyping
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 4 Sep 2018 (actual)
- Primary completion
- 31 Oct 2018 (actual)
- Study completion
- 31 Oct 2018 (actual)
- First posted
- 18 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
12 healthy male subjects meeting the inclusion and exclusion criteria were enrolled. On day 1, they ingested a capsule containing the Basel Cocktail (1A2: caffeine, 2B6: efavirenz, 2C9: flurbiprofen, 2C19: omeprazole, 2D6: metoprolol, 3A4: midazolam) in fastened state. Blood samples were withdrawn over 24 hours and the AUC ratios between metabolite and parent were calculated to determine the phenotype.
Probands began metamizole treatment (3000 mg/day) at the day of the 24h measurement. After 3-4 day, probands were returning to the facility to ensure safety during the metamizole treatment, blood cell count and metamizole metabolites were measured. After the 7 days of treatment, probands were exposed again to the Basel Cocktail in a fastened state. Probands were still exposed to metamizole to ensure potential inhibition. 24 hours plasma samples were withdrawn, area under the curve (AUC) ratios were calculated and compared to the basal state. After an end of study visit on the day of the 24h blood sample (following the second study day), probands were discharged.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Two phase study, before-after comparison
| Arm | Type | Receives |
|---|---|---|
| Study population | Other | Drug: MetamizoleAll participants |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetamizoleOne week treatment with metamizole (500 mg tablets, 2-2-2) | Drug | Study population |
Primary outcome
Effect on AUC ratio between parent and metabolite
Time frame: 12 hours
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
Cmax
Time frame: 24 hours
Maximal Concentration in plasma of parent and metabolite
tmax
Time frame: 24 hours
time to reach Cmax
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephan Krähenbühl, Prof. Dr. MD principal investigator
Head of Clinical Pharmacology, University Hospital Basel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metamizole in people with Inhibition and Induction, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect on AUC ratio between parent and metabolite (time frame: 12 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2019.