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

Primary Purpose

Diabetic Polyneuropathy, Postherpetic Neuralgia

Status

Withdrawn

Phase

Phase 4

Locations

Finland

Study Type

Interventional

Intervention

Tramadol

Duloxetine

Pregabalin

About this trial

This is an interventional treatment trial for Diabetic Polyneuropathy focused on measuring Pharmacokinetics, Pharmacodynamics, Interaction, tramadol, duloxetine, pregabalin

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Duloxetine and tramadol

Pregabalin and tramadol

Arm Description

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.

Outcomes

Primary Outcome Measures

Concentration of O-desmethyltramadol

Secondary Outcome Measures

Plasma 5-HT concentration

Platelet function

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.

Use of rescue medication

Behavioral serotonergic effects

Concentration of O-desmethyltramadol

Full Information

NCT ID

NCT01116531

First Posted

April 19, 2010

Last Updated

May 30, 2013

Sponsor

Turku University Hospital

Collaborators

University of Helsinki

1. Study Identification

Unique Protocol Identification Number

NCT01116531

Brief Title

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

2. Study Status

Record Verification Date

May 2013

Overall Recruitment Status

Withdrawn

Study Start Date

April 2010 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

December 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Turku University Hospital

Collaborators

University of Helsinki

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Polyneuropathy, Postherpetic Neuralgia

Keywords

Pharmacokinetics, Pharmacodynamics, Interaction, tramadol, duloxetine, pregabalin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Duloxetine and tramadol

Arm Type

Active Comparator

Arm Description

Arm Title

Pregabalin and tramadol

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tramadol

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Duloxetine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Pregabalin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Concentration of O-desmethyltramadol

Time Frame

3 weeks

Secondary Outcome Measure Information:

Title

Plasma 5-HT concentration

Time Frame

baseline, 1, 2 and 3 weeks

Title

Platelet function

Time Frame

baseline and 3 weeks

Title

Pain intensity

Description

Time Frame

daily for 3 weeks

Title

Use of rescue medication

Time Frame

1,2 and 3 weeks

Title

Behavioral serotonergic effects

Time Frame

1, 2 and 3 weeks

Title

Concentration of O-desmethyltramadol

Time Frame

baseline, 1 and 2 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Klaus T Olkkola, MD,PhD,Prof

Organizational Affiliation

Turku University Hospital and Turku University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital

City

Turku

ZIP/Postal Code

20520

Country

Finland

12. IPD Sharing Statement

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

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