Effect of Duloxetine and Venlafaxine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol: A Three-phase Randomized Balanced Cross-over Study in Healthy Volunteers

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Turku University Hospital

ClinicalTrials.gov Identifier:

NCT01443520

First received: September 28, 2011

Last updated: May 21, 2012

Last verified: May 2012

History of Changes

Tracking Information
First Received Date ^ICMJE	September 28, 2011
Last Updated Date	May 21, 2012
Start Date ^ICMJE	October 2011
Primary Completion Date	January 2012 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: September 28, 2011)	Concentration of tramadol and its metabolites in plasma [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours after administration of tramadol ] [ Designated as safety issue: No ]
Original Primary Outcome Measures ^ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01443520 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: September 28, 2011)	Serotonin concentrations [ Time Frame: 0, 4 and 8 hours after tramadol administration ] [ Designated as safety issue: No ] Serotonin concentrations will be analyzed with chromatographical methods from the blood samples drawn 0, 4 and 8 hours after tramadol administration Pharmacodynamic effects [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after administration of tramadol ] [ Designated as safety issue: No ] The psychomotor effects of tramadol will be assessed with the measurement of pupil size with Cogan's pupillometer, Maddox wing test and digit symbol substitution test Analgesia [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the administration of tramadol ] [ Designated as safety issue: No ] The analgesic effect of tramadol will be evaluated using the cold pressor test. Briefly, the subject's hand is immersed into ice-cold water of + 4° C up to the wrist. The subject is told to keep his or her hand in the water and to report when the cold sensation becomes painful. Cold pain threshold is defined as the latency from the immersion of the hand to the subject's first report of pain. Cold pain intensity is assessed at 30 s intervals following immersion of the hand in cold water for up to 60s . A verbal numerical rating scale of 0-100 will be used.
Original Secondary Outcome Measures ^ICMJE	Same as current
Current Other Outcome Measures ^ICMJE
Original Other Outcome Measures ^ICMJE

Descriptive Information
Brief Title ^ICMJE	Effect of Duloxetine and Venlafaxine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol: A Three-phase Randomized Balanced Cross-over Study in Healthy Volunteers
Official Title ^ICMJE
Brief Summary	Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. After oral administration, tramadol is rapidly and almost completely absorbed. Tramadol is extensively metabolised by O- and N-demethylation, which are catalysed by the liver CYP-450 enzymes. O-desmethyltramadol is an active metabolite and its formation is catalysed by CYP2D6. This study is aimed to investigate the possible interaction of oral tramadol with duloxetine and venlafaxine. Duloxetine is known to inhibit CYP2D6. Twelve healthy male or female adult non-smoking volunteers aged 18-40 years with body weights within ±15% of the ideal weight for height are taken into the study. Primary endpoints of the study are plasma concentrations of tramadol and its metabolites.
Detailed Description
Study Type ^ICMJE	Interventional
Study Phase	Phase 4
Study Design ^ICMJE	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Basic Science
Condition ^ICMJE	Healthy
Intervention ^ICMJE	Drug: Placebo The subjects will be given orally placebo twice a day for 8 days prior to the study. Drug: Duloxetine The subjects will be given orally duloxetine 30mg twice a day for 8 days prior to the study. Drug: Venlafaxine The subjects will be given orally venlafaxine 37,5mg twice a day for 8 days prior to the study.
Study Arm (s)	Placebo Comparator: Placebo Intervention: Drug: Placebo Active Comparator: Duloxetine Intervention: Drug: Duloxetine Active Comparator: Venlafaxine Intervention: Drug: Venlafaxine
Publications *
* 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
Enrollment ^ICMJE	12
Completion Date	January 2012
Primary Completion Date	January 2012 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	Inclusion Criteria: Healthy volunteers Age 18-40 Body weight within ±15% of the ideal weight for height Exclusion Criteria: A previous history of intolerance to the study drugs or to related compounds and additives Concomitant drug therapy of any kind for at least 14 days prior to the study Existing or recent significant disease History of hematological, endocrine, metabolic or gastrointestinal disease, including gut motility disorders History of asthma or any kind of drug allergy Previous or present alcoholism, drug abuse, psychological or other emotional problems that are likely to invalidate informed consent, or limit the ability of the subject to comply with the protocol requirements A positive test result for urine toxicology A "yes" answer to any one of the Abuse Questions Pregnancy or nursing Donation of blood for 4 weeks prior and during the study Special diet or life style conditions which would compromise the conditions of the study or interpretation of the results Participation in any other studies involving investigational or marketed drug products concomitantly or within one month prior to the entry into this study Smoking for one month before the start of the study and during the whole study period Any history of coagulation abnormality, also in first degree relatives
Gender	Both
Ages	18 Years to 40 Years
Accepts Healthy Volunteers	Yes
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	Finland

Administrative Information
NCT Number ^ICMJE	NCT01443520
Other Study ID Numbers ^ICMJE	97/180/2011, 2011-003259-20
Has Data Monitoring Committee
Responsible Party	Turku University Hospital
Study Sponsor ^ICMJE	Turku University Hospital
Collaborators ^ICMJE
Investigators ^ICMJE
Information Provided By	Turku University Hospital
Verification Date	May 2012
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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