Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Metamizole (Dipyrone) on Renal Function in Salt-depleted Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01995006
Recruitment Status : Completed
First Posted : November 26, 2013
Last Update Posted : April 17, 2015
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE November 20, 2013
First Posted Date  ICMJE November 26, 2013
Last Update Posted Date April 17, 2015
Study Start Date  ICMJE January 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 25, 2013)
Glomerular filtration rate (GFR) [ Time Frame: up to 7 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
  • 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 ]
    • 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-∞)
Original Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2013)
  • Effective renal plasma flow (ERPF) [ Time Frame: Day 1 and 7 ]
  • 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 ]
    • 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-∞)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Metamizole (Dipyrone) on Renal Function in Salt-depleted Healthy Subjects
Official Title  ICMJE 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
Brief 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). 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: metamizole
    metamizol tablets (500mg): 1000mg TID during 7 days
    Other Name: dipyrone
  • Drug: Naproxen
    Naproxen tablets (500mg): 500 mg BID during 7 days
    Other Name: Naproxen sodium
Study Arms  ICMJE
  • Experimental: Metamizole
    Metamizole 1000mg TID Day 1 till Day 7
    Intervention: Drug: metamizole
  • Active Comparator: Naproxen
    Naproxen 500 mg BID Day 1 till Day 7
    Intervention: Drug: Naproxen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 12, 2014)
15
Original Estimated Enrollment  ICMJE
 (submitted: November 25, 2013)
16
Actual Study Completion Date  ICMJE April 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • 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

Exclusion Criteria:

  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01995006
Other Study ID Numbers  ICMJE EKBB 264/13
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Basel, Switzerland
Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Manuel Haschke, PD University Hospital, Basel, Switzerland
PRS Account University Hospital, Basel, Switzerland
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP