Paroxetines Effect on Tramadols Metabolism and Pharmakodynamics: a Dose Response Study

NCT00785603 | Unknown Phase 4 DMC

• 1 other identifier: AKF-374
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to examine the connection between the dose of paroxetine and the effect of paroxetine on tramadols metabolism and thereby the effect of tramadol on the median pupil size. In the study 12 healthy volunteers are going through 5 phases where they are suppose to consume a determined dose of tramadol and 5 various doses of paroxetine corresponding to the 5 phases. Fig 1. phases 1 2 3 4 5 Dosis Tramadol mg 50 50 50 50 50 Dosis Paroxetine mg Placebo 10 20 30 50 Paroxetin / placebo 2 ½ placebo 2 placebo 1 ½ placebo 1 placebo tablets ½ paroxetine 1 paroxetine 1 ½ paroxetine 2 ½ paroxetine Fig. 1 summary of the 5 phases There is a variation in the time where maximal plasma concentration is obtained in consumption of respectively tramadol (1 - 2 hours) and paroxetine (6 hours). For that reason there has to be at least 6 hours between the administration of paroxetine and tramadol. The healthy volunteer brings the research medicine home and consumes it before bedtime the night before the day of the study. At eight o'clock next morning the healthy volunteer arrives to the first pupil measurement and consumption of tramadol. Tree hours later the next pupil measurement is carried through. The healthy volunteer accumulates his or her urine until 2 pm. As paroxetine is a irreversible inhibitor of the enzyme CYP2D6 there has to go at least 14 days before the next phase takes place. In that amount of time there can be recreated a new pool of enzyme.

Conditions

Depression; Pain

Keywords

Depression; pain; CYP2D6; interactions; Pupillometry; Tramadol; Paroxetine; MR-ratio

Outcome Measures

Primary Outcomes (1)

• Primary endpoint Pupil measurements Min. diameter mm Reduktion % Latenstime s Maks. constriktions velocity mm/s constriktions velocity mm/s Dilatation velocity mm/s

  3 hours

Secondary Outcomes (1)

• MR-ratio

  8 hours

Interventions

Paroxetine DRUG

tablets of 20 mg paroxetine

Also known as: Paroxetin, copyfarm

Paroxetin placebo DRUG

capsules with lactulose to hide, whether the volunteer are receiving 0, 10, 20, 30 or 50 mg paroxetine

Tramadol DRUG

Capsules of 50 mg tramadol

Also known as: Nobligan

Eligibility Criteria

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

You may qualify if:

• Healthy volunteers judged from the medical anamnesis and examination, inclusive a laboratory examination.
• Signed written approval and authorization, witch give relevant people (the GCP-unit, the the Danish Medicines Agency and the ethics committee of Southern Denmark) access to documents and data of interest to this study
• Age: 18 - 45 years
• Women must use one of the Danish Medicines Agency defined safe contraception. A negative pregnancy test has to ensure that the volunteers are not pregnant at the start of the study
• All the volunteers have to be phenotyped as CYP2D6 extensive metabolizer (EM) by a "tramadol test": the volunteer ingest 50 mg tramadol and all urine is collected fore 8 hours. By a HPLC method the metabolic ratio (MR) of (-)-M1/(+)-M1 is determined in the urine. Volunteers with a MR-ratio smaller than 2 is defined as CYP2D6 EM's

You may not qualify if:

• Any clinical significant observation at the medical- or laboratory examination
• Daily use of medicine or alcohol. Periodic use of medicine can be accepted after individual valuation by a doctor
• Allergy or intolerance to paroxetine or tramadol
• Former participation in a clinical study in the last 3 months

Sponsors & Collaborators

• University of Southern Denmark: lead

MeSH Terms

Conditions

Depression; Pain

Interventions

Paroxetine; Tramadol

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids

Study Officials

• Anette Green Nielsen, Stud. pharm

  Institut of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 4, 2008
• First Posted: November 5, 2008
• Study Start: August 1, 2008
• Primary Completion: August 1, 2008
• Study Completion: February 1, 2009
• Last Updated: February 13, 2009

Record last verified: 2009-02