Clinical trial NCT01116531: Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin
Official title: Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin: a Randomized Controlled Flexible-dose Study in Patients With Neuropathic Pain
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Diabetic Polyneuropathy
Postherpetic Neuralgia
Keywords: Pharmacokinetics
Pharmacodynamics
Interaction
tramadol
duloxetine
pregabalin
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
Collaborators: name: University of Helsinki
First posted: 2010-05-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. Treatment of neuropathic pain often requires a combination of pain medications due to the complex nature of neuropathic pain and frequent inadequate response to drug treatment. Common drugs used concomitantly with tramadol are SNRI antidepressant duloxetine and anticonvulsants such as pregabalin. Both tramadol and duloxetine have serotonergic effects and duloxetine has also a potential to inhibit metabolism of tramadol. The objective of the study is to investigate the pharmacokinetics and pharmacodynamic interaction of oral tramadol with duloxetine and pregabalin in patients with chronic neuropathic pain due to postherpetic neuralgia or diabetic polyneuropathy. All subjects will receive tramadol and duloxetine or tramadol and pregabalin in a randomized double-blind order. Primary end point is O-desmethyltramadol concentration.


Eligibility criteria: Inclusion Criteria:

* Chronic (≥ 6 months) neuropathic pain due to postherpetic neuralgia or diabetic polyneuropathy
* Pain intensity ≥ 4 on a numerical scale of 0-10
* Informed consent

Exclusion Criteria:

* Clinically significant abnormalities in laboratory screening
* Pregnancy
* Depression
* Use of strong opioids (morphine, oxycodone, fentanyl, hydromorphone, methadone)
* A previous history of intolerance or allergy to the study drugs or to related compounds and additives
* Existing or history of seizures, haematological disorders, clinically significant renal, hepatic, respiratory, cardiac or psychiatric disease, dementia, drug allergy
* Previous or present alcoholism, drug abuse, psychological or other emotional problems or cognitive impairment that are likely to invalidate informed consent or limit the ability of the subject to comply with protocol requirements
* Concomitant drug therapy known to cause significant enzyme induction or inhibition of CYP 1A2, 2D6, 3A4, 2B6, drugs metabolised by CYP2D6 enzyme, antidepressants, MAO-inhibitors, non-steroidal anti-inflammatory analgesics.

Primary outcomes:
measure: Concentration of O-desmethyltramadol
timeFrame: 3 weeks
Secondary outcomes:
measure: Plasma 5-HT concentration
timeFrame: baseline, 1, 2 and 3 weeks
measure: Platelet function
timeFrame: baseline and 3 weeks
measure: Pain intensity
timeFrame: daily for 3 weeks
measure: Use of rescue medication
timeFrame: 1,2 and 3 weeks
measure: Behavioral serotonergic effects
timeFrame: 1, 2 and 3 weeks
measure: Concentration of O-desmethyltramadol
timeFrame: baseline, 1 and 2 weeks
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital
Study officials:
affiliation: Turku University Hospital and Turku University
name: Klaus T Olkkola, MD,PhD,Prof
role: PRINCIPAL_INVESTIGATOR
References: