Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin

Phase 4

Withdrawn

• Conditions: Diabetic Polyneuropathy; Postherpetic Neuralgia
• Interventions: Drug: Tramadol; Drug: Duloxetine; Drug: Pregabalin

• Registration Number: NCT01116531
• Lead Sponsor: Turku University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-04-19
• Study First Submitted QC: 2010-05-03
• Study First Posted: 2010-05-05
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Status Verified: 2013-05
• Last Update Submitted: 2013-05-30
• Last Update Posted: 2013-05-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Duloxetine and tramadol	Tramadol	To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy.
Duloxetine and tramadol	Duloxetine	To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy.
Pregabalin and tramadol	Tramadol	To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy.
Pregabalin and tramadol	Pregabalin	To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy.

Primary Outcome Measures

Name	Time	Method
Concentration of O-desmethyltramadol	3 weeks

Secondary Outcome Measures

Name	Time	Method
Platelet function	baseline and 3 weeks
Plasma 5-HT concentration	baseline, 1, 2 and 3 weeks
Pain intensity	daily for 3 weeks	Pain intensity will be rated by the subjects on a numerical 11-point rating scale of 0-10 (NRS) with 0 meaning "no pain" and 10 meaning "pain as bad as you can imagine". The subjects will be asked to rate pain intensity on the average over the past 24 hours. Pain intensity will be recorded at each study visit and daily by the subject using a pain diary.
Use of rescue medication	1,2 and 3 weeks
Behavioral serotonergic effects	1, 2 and 3 weeks
Concentration of O-desmethyltramadol	baseline, 1 and 2 weeks

Trial Locations

Locations (1)

Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital; 🇫🇮 Turku, Finland