HealthyPhase 1NCT01995006
Effect of Metamizole (Dipyrone) on Renal Function in Salt-depleted Healthy Subjects
A Phase 1 study testing metamizole and Naproxen in people with Healthy, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
The planned study is a single-center, randomized, open-label parallel group study in 16 healthy male subjects. Study subjects will be randomly allocated either to the metamizole group (1) or to the naproxen group (2). 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
- Healthy
- What is being tested?
- metamizole and Naproxen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2014to Apr 2014
- 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 male subjects aged between 18 and 45 years (inclusive) at screening
- BMI between 18 and 28 kg/m2 (inclusive) and body weight at least 50 kg at screening.
- systolic blood pressure (SBP): 100-140 mmHg, diastolic blood pressure (DBP): 60-90 mmHg and heart rate (HR): 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.
- 12-lead ECG without clinically relevant abnormalities at screening.
- Signed informed consent prior to any study-mandated procedure.
Show all 9Show fewer
- Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening.
- Ability to communicate well with the investigator and to understand and comply with the requirements of the study.
- leading arm right = writing with right hand
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 treatment with any prescribed or over-the-counter (OTC) medication (including herbal medicines such as St John's Wort) within 2 weeks prior to the intended start of the study.
- Legal incapacity or limited legal capacity at screening.
Show all 11Show fewer
- Positive results from urine drug screen at screening.
- History or clinical evidence of any disease (e.g. GIT-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 Aspirin or other NSAIDs or any excipients of the drug formulations.
- Known food allergy, which make the adherence to the diet impossible
- 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.
About this study
Official title: Effect of Metamizole on Renal Function in Salt-depleted Healthy Subjects Single-center, Randomized, Open, Controlled Parallel-group Study to Investigate the Effects of Oral Metamizole or Naproxen on Renal Function in Healthy Male Salt-depleted Subjects
The planned study is a single-center, randomized, open-label parallel group study in 16 healthy male subjects. Study subjects will be randomly allocated either to the metamizole group (1) or to the naproxen group (2). All participants will start with a low sodium diet (approximately 50 mmol Na+ per day) 7 days before the first drug intake and maintain the diet until the end of the study (14 days in total). Salt-depletion is an accepted model to enhance production of vasodilatory prostaglandins and to increase renal sensitivity to prostaglandin inhibition. On the first day of treatment (Day 1), a single dose of metamizole or naproxen will be administered to investigate the effects after a single dose and to collect single dose pharmacokinetic profiles. Starting on Day 2, all participants will receive therapeutic doses, i.e. 1000 mg metamizole 'ter in die' (TID, three times a day) or 500 mg naproxen 'bis in die' (BID, twice a day) for one week and on Day 7 pharmacokinetics and pharmacodynamics effects will be assessed under near steady-state conditions.
The primary objective is the characterization of the renal effects of metamizole by determination of the glomerular filtration rate (GFR) using the inulin clearance. Secondary objectives are the characterization of the urinary excretion of prostaglandin E2 (PGE2) and the prostaglandin I2 (PGI2) metabolite 6-keto-prostaglandin F1 (PGF1)alpha as well as the urinary excretion of sodium and potassium.
Overall, clinical experience suggests better renal tolerability of metamizole possibly due to less potent COX-inhibition compared to classical nonsteroidal antiinflammatory drugs (NSAIDs). If this could be confirmed, metamizole would be a valuable alternative for treatment of painful conditions in patients with impaired renal function. Therefore, the aim of this study is to examine the effects of metamizole on renal function in comparison with the non-specific COX-inhibitor naproxen.
- Conditions
- Healthy
- Being tested
- metamizole, Naproxen
- Keywords
- Effect, metamizole, salt-depleted, subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metamizoleDrug
Also called dipyrone
metamizol tablets (500mg): 1000mg TID during 7 days
NaproxenDrug
Also called Naproxen sodium
Naproxen tablets (500mg): 500 mg BID during 7 days
| Study group | Role | What they receive |
|---|---|---|
| Metamizole | Experimental | Metamizole 1000mg TID Day 1 till Day 7 Receives: Drug: metamizole |
| Naproxen | Active comparator | Naproxen 500 mg BID Day 1 till Day 7 Receives: Drug: Naproxen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glomerular filtration rate (GFR)
Measured: up to 7 days
Secondary outcomes (3)
Measurement of the urinary excretion of the prostaglandin E2 (PGE2) and of the prostacyclin (PGI2) metabolite 6-keto-PGF1alpha
Measured: Day 1 and Day 7
Measurement of urine levels of sodium, potassium and creatinine and the urinary output
Measured: Day 1 and Day 7
Plasma pharmacokinetic (PK) parameters of each drug will be derived either directly from observed data or by analysis of the concentration-time profiles
- The maximum plasma concentration (Cmax) and time to reach Cmax (tmax)
- The terminal elimination rate constant with the respective half-life (t½)
- The area under the plasma concentration-time curve from zero to different time points (AUC0-24, AUC0-∞)
Measured: Day 1 and Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2013 (estimated)
- Study startJan 2014
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Manuel Haschke, PD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01995006
- Sponsor's protocol ID
- EKBB 264/13
- Status last verified
- Apr 2015
- First submitted
- 20 Nov 2013
- Last updated
- 17 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Metamizole on Renal Function in Salt-depleted Healthy Subjects Single-center, Randomized, Open, Controlled Parallel-group Study to Investigate the Effects of Oral Metamizole or Naproxen on Renal Function in Healthy Male Salt-depleted Subjects
- ClinicalTrials.gov ID
- NCT01995006
- Acronym / sponsor ID
- EKBB 264/13
- Conditions
- Healthy
- Keywords
- Effect, metamizole, salt-depleted, subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 26 Nov 2013 (estimated)
- 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.
The planned study is a single-center, randomized, open-label parallel group study in 16 healthy male subjects. Study subjects will be randomly allocated either to the metamizole group (1) or to the naproxen group (2). All participants will start with a low sodium diet (approximately 50 mmol Na+ per day) 7 days before the first drug intake and maintain the diet until the end of the study (14 days in total). Salt-depletion is an accepted model to enhance production of vasodilatory prostaglandins and to increase renal sensitivity to prostaglandin inhibition. On the first day of treatment (Day 1), a single dose of metamizole or naproxen will be administered to investigate the effects after a single dose and to collect single dose pharmacokinetic profiles. Starting on Day 2, all participants will receive therapeutic doses, i.e. 1000 mg metamizole 'ter in die' (TID, three times a day) or 500 mg naproxen 'bis in die' (BID, twice a day) for one week and on Day 7 pharmacokinetics and pharmacodynamics effects will be assessed under near steady-state conditions.
The primary objective is the characterization of the renal effects of metamizole by determination of the glomerular filtration rate (GFR) using the inulin clearance. Secondary objectives are the characterization of the urinary excretion of prostaglandin E2 (PGE2) and the prostaglandin I2 (PGI2) metabolite 6-keto-prostaglandin F1 (PGF1)alpha as well as the urinary excretion of sodium and potassium.
Overall, clinical experience suggests better renal tolerability of metamizole possibly due to less potent COX-inhibition compared to classical nonsteroidal antiinflammatory drugs (NSAIDs). If this could be confirmed, metamizole would be a valuable alternative for treatment of painful conditions in patients with impaired renal function. Therefore, the aim of this study is to examine the effects of metamizole on renal function in comparison with the non-specific COX-inhibitor naproxen.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metamizole | Experimental | Drug: metamizoleMetamizole 1000mg TID Day 1 till Day 7 |
| Naproxen | Active comparator | Drug: NaproxenNaproxen 500 mg BID Day 1 till Day 7 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Healthy male subjects aged between 18 and 45 years (inclusive) at screening
- BMI between 18 and 28 kg/m2 (inclusive) and body weight at least 50 kg at screening.
- systolic blood pressure (SBP): 100-140 mmHg, diastolic blood pressure (DBP): 60-90 mmHg and heart rate (HR): 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.
- 12-lead ECG without clinically relevant abnormalities at screening.
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 treatment with any prescribed or over-the-counter (OTC) medication (including herbal medicines such as St John's Wort) within 2 weeks prior to the intended 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 |
|---|---|---|
| metamizoleAlso: dipyronemetamizol tablets (500mg): 1000mg TID during 7 days | Drug | Metamizole |
| NaproxenAlso: Naproxen sodiumNaproxen tablets (500mg): 500 mg BID during 7 days | Drug | Naproxen |
Primary outcome
Glomerular filtration rate (GFR)
Time frame: up to 7 days
3 secondary outcomes
Measurement of the urinary excretion of the prostaglandin E2 (PGE2) and of the prostacyclin (PGI2) metabolite 6-keto-PGF1alpha
Time frame: Day 1 and Day 7
Measurement of urine levels of sodium, potassium and creatinine and the urinary output
Time frame: Day 1 and Day 7
Plasma pharmacokinetic (PK) parameters of each drug will be derived either directly from observed data or by analysis of the concentration-time profiles
Time frame: Day 1 and Day 7
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 17 Apr 2015.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
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.
Manuel Haschke, PD principal investigator
University Hospital, Basel, Switzerland
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 and Naproxen in people with Healthy, 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 9 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 17 Apr 2015. 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?
Glomerular filtration rate (GFR) (time frame: up to 7 days). 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 17 Apr 2015.