Pharmacokinetics, Metabolism and Analgesic Effects of Flupirtine
1 other identifier
interventional
36
1 country
1
Brief Summary
Flupirtine is metabolized in-vitro via carbamate cleavage and N acetylation to glucuronides and mercapturic acid derivatives. The formation of reactive, toxic intermediate products may be influenced by genetic polymorphisms of the involved conjugative metabolic pathways. So the purpose of this study is to measure pharmacokinetics, metabolism and analgesic effects of flupirtine in dependence on the function of NAT2, UGT1A1 and GSTP1.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 pain
Started May 2008
Typical duration for phase_1 pain
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2009
CompletedFirst Submitted
Initial submission to the registry
August 28, 2012
CompletedFirst Posted
Study publicly available on registry
August 30, 2012
CompletedAugust 30, 2012
August 1, 2012
1 year
August 28, 2012
August 28, 2012
Conditions
Outcome Measures
Primary Outcomes (3)
bioavailability (F)
ratio of the area under the concentration time curve after oral to intravenous administration of study medication
before and 0.5,1,1.5,2,2.5,3,3.5,4,5,6,8,10,12,16,24,48,72,96,120 h after administration of study medication
delayed onset of muscle soreness (DOMS)
For pain measurements, muscle pain is stimulated by standing on tiptoes of one leg for 30 s, which requires a constriction of the affected calf muscles. The other leg is lifted and the subjects are allowed to hold on to a table to keep their balance. The pain intensity during this stimulation is then rated by means of a 10 cm visual analogue scale (VAS). The VAS is extended from "no pain" to "intolerable pain" with a precision of 1 mm.
before and 2, 4, 6, 8 h after study medication
electric pain threshold
A painful 5 Hz sine waves electrical stimuli (increase of intensity 0.2 mA/s, from 0 to 20 mA), will be applied via two gold electrodes placed on the medial and lateral side of the distal phalangeal joint (middle finger of the left hand as default-testing site). During testing, subjects keep a button continuously pressed until they find the pain intolerably and interrupt the current by releasing the button. The electrical current at which this occurred is defined as pain tolerance, the target parameter of this pain model. Each value of pain tolerance is the median of five subsequent measurements obtained at an interval of 1 min.
before and 2, 4, 6, 8 h (and 10, 12 h on study day 8) after study medication and on study days 1,2,3,4,5,6,7
Secondary Outcomes (2)
amount of excretion (Ae) in urine
in 24 h intervals for 3 days
amount of excretion (Ae) of feces
5 day sampling period
Study Arms (3)
flupirtine per os single dose
ACTIVE COMPARATOR100 mg flupirtine per os, pharmacokinetics of flupirtine, induce delayed onset of muscle soreness (DOMS), electric pain measurement
flupirtine intravenous
ACTIVE COMPARATOR100 mg flupirtine intravenous, pharmacokinetics of flupirtine, induce delayed onset of muscle soreness (DOMS), electric pain measurement
flupirtine per os steady state
ACTIVE COMPARATOR400 mg flupirtine per os, pharmacokinetics of flupirtine, electric pain measurement
Interventions
Administration of 100 mg flupirtine intravenous (3 mg solution intravenously, 1 vial Kadadolon® inject)
Administration of 100 mg flupirtine per os (1 capsule Kadadolon®)
Administration of 400 mg flupirtine (1 Kadadolon® S long retard tablet)
The DOMS exercise protocol consists of two sets of 50 concentric/eccentric contractions of the calf muscles of one leg with a rest of 5 min in-between. The exercise is performed 22-26 h prior to medication. For pain measurements, muscle pain is stimulated by standing on tiptoes of one leg for 30 s, which requires a constriction of the affected calf muscles. The other leg is lifted and the subjects are allowed to hold on to a table to keep their balance. The pain intensity during this stimulation is then rated by means of a 10 cm visual analogue scale (VAS). The VAS is extended from "no pain" to "intolerable pain" with a precision of 1 mm. The stimulation is repeated with the other leg. The sequence of the legs is chosen randomly.
The method has been described to be sensitive to quantify analgesic opioid effects. Painful 5 Hz sine waves electrical stimuli (increase of intensity 0.2 mA/s, from 0 to 20 mA), which predominantly activate C-fibres, will be applied via two gold electrodes placed on the medial and lateral side of the distal phalangeal joint (middle finger of the left hand as default-testing site). During testing, subjects keep a button continuously pressed until they find the pain intolerably and interrupt the current by releasing the button. The electrical current at which this occurred is defined as pain tolerance, the target parameter of this pain model. Each value of pain tolerance is the median of five subsequent measurements obtained at an interval of 1 min.
Eligibility Criteria
You may qualify if:
- age: 18 - 45 years
- sex and genetics: male and female genotyped for NAT2, UGT1A1 and GSTP1
- ethnic origin: Whites
- body weight: 19 - 27 kg/m²
- good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
- written informed consent
You may not qualify if:
- existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of the study drug
- existing or further obstructive lung disease (e.g. bronchial asthma)
- myasthenia gravis
- existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of the study drug
- existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of the study drug
- acute or chronic diseases which could affect drug absorption or metabolism
- history of any serious psychological disorder
- drug or alcohol dependence
- positive drug screening or -only in suspicious case- positive alcohol test
- smokers of 10 or more cigarettes per day
- positive screening results for HIV, HBV and HCV
- volunteers who are on a diet which could affect the pharmacokinetics of the drug (vegetarian)
- heavy tea or coffee drinkers (more than 1l per day)
- lactation and pregnancy test positive or not performed
- volunteers suspected or known not to follow instructions
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Medicine Greifswaldlead
- AWD.pharma GmbH & Co. KGcollaborator
Study Sites (1)
Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald
Greifswald, Mecklenburg-Vorpommern, 17487, Germany
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr. W. Siegmund, MD
Study Record Dates
First Submitted
August 28, 2012
First Posted
August 30, 2012
Study Start
May 1, 2008
Primary Completion
May 1, 2009
Study Completion
June 1, 2009
Last Updated
August 30, 2012
Record last verified: 2012-08