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
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Placebo
Drug: Duloxetine
Drug: Venlafaxine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science

Resource links provided by NLM:


Further study details as provided by Turku University Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Enrollment: 12
Study Start Date: October 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
The subjects will be given orally placebo twice a day for 8 days prior to the study.
Active Comparator: Duloxetine Drug: Duloxetine
The subjects will be given orally duloxetine 30mg twice a day for 8 days prior to the study.
Active Comparator: Venlafaxine Drug: Venlafaxine
The subjects will be given orally venlafaxine 37,5mg twice a day for 8 days prior to the study.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01443520

Locations
Finland
Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital
Turku, Finland
Sponsors and Collaborators
Turku University Hospital
  More Information

No publications provided

Responsible Party: Turku University Hospital
ClinicalTrials.gov Identifier: NCT01443520     History of Changes
Other Study ID Numbers: 97/180/2011, 2011-003259-20
Study First Received: September 28, 2011
Last Updated: May 21, 2012
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by Turku University Hospital:
Pharmacokinetics
Pharmacodynamics

Additional relevant MeSH terms:
Venlafaxine
Duloxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic Uptake Inhibitors
Adrenergic Agents
Dopamine Uptake Inhibitors
Dopamine Agents

ClinicalTrials.gov processed this record on August 27, 2014