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

Postherpetic Neuralgia Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01116531
• Other study ID #: 60/180/2009
• Status: Withdrawn
• Phase: Phase 4
• First received: April 19, 2010
• Last updated: May 30, 2013
• Start date: April 2010
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: Turku University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Diabetic Polyneuropathy
• Neuralgia, Postherpetic
• Polyneuropathies
• Postherpetic Neuralgia

Intervention

Drug:
• Tramadol
Initial dose of oral tramadol (depottabl Tramal retard, Orionpharma, Finland) will be 100mg once daily. If the subject is currently on opioid treatment with codeine, tramadol or buprenorphine, the opioid treatment will be stopped, and an equal dose of tramadol will be used as the initial dose. The dose will be titrated on visits V2 and V3 based on the adequacy of pain relief and tolerability. If pain intensity = 4 on a numeric rating scale of 0-10 during V2 and V3 and tramadol is well tolerated, the daily dose will be increased by 100mg. The maximum daily dose of 400 mg tramadol will not be exceeded. If the subject does not tolerate the initial dose of tramadol, he/she will be dropped out of the study and replaced by another patient.
• Duloxetine
The initial dose of duloxetine (Cymbalta, Eli Lilly, USA) will be 30mg once daily. The dose will be titrated on V2 based on the adequacy of pain relief and tolerability. If pain intensity during V2 is < 4 on a scale of 0-10, the dose of duloxetine dose will be 30mg daily throughout the study. If pain intensity is = 4 on a numeric rating scale of 0-10 and duloxetine is well tolerated, the daily dose will be increased to 60mg once daily. If the subject does not tolerate the initial dose of duloxetine, he/she will be dropped out of the study and replaced by another patient.
• Pregabalin
The initial dose of pregabalin (Lyrica, Pfizer, USA) will be 75mg twice a day. The dose will be titrated on V2 based on the adequacy of pain relief and tolerability. If pain intensity during V2 is < 4 on a scale of 0-10, the initial dose of pregabalin dose will be continued. If pain intensity is = 4 on a numeric rating scale of 0-10 and pregabalin is well tolerated, the daily dose will be increased to 150mg twice a day. If the subject does not tolerate the initial dose of pregabalin, he/she will be dropped out of the study and replaced by another patient.

Locations

Country	Name	City	State
Finland	Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital	Turku

Sponsors (2)

Lead Sponsor	Collaborator
Turku University Hospital	Helsinki University

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of O-desmethyltramadol		3 weeks	No
Secondary	Plasma 5-HT concentration		baseline, 1, 2 and 3 weeks	No
Secondary	Platelet function		baseline and 3 weeks	No
Secondary	Pain intensity	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.	daily for 3 weeks	No
Secondary	Use of rescue medication		1,2 and 3 weeks	No
Secondary	Behavioral serotonergic effects		1, 2 and 3 weeks	No
Secondary	Concentration of O-desmethyltramadol		baseline, 1 and 2 weeks	No