Comparison of Increasing Doses of Tapentadol Versus a Combination of Tapentadol and Pregabalin

NCT ID: NCT01352741

Last Updated: 2019-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 622 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2012-01-31

Brief Summary

The main objective of the study is to evaluate the effectiveness, safety, and tolerability of increasing doses of tapentadol prolonged release (PR) (500 mg per day) versus a combination of tapentadol PR (300 mg per day) and pregabalin (to 300 mg per day) in subjects requiring additional analgesia after titration to tapentadol PR 300 mg per day.

This is a clinical effectiveness trial designed to establish a link between anticipated clinical outcomes and the clinical practice by means of selected measures of clinical and subject reported outcomes. Since, severe low back pain with a neuropathic component, the targeted study population, is frequently treated with a combination therapy (monotherapy is often not effective enough) it is of interest to determine if tapentadol alone (combining 2 mechanisms of action in a single molecule) could be as effective as a combination of tapentadol plus pregabalin. Furthermore, the tolerability profiles of monotherapy versus combination are of interest.

Detailed Description

Participants with a diagnosis of chronic low back pain (defined as pain lasting for at least 3 month) and requiring a strong analgesic (World Health Organization [WHO] Step III) as judged by the investigator and having a positive or unclear score using the painDETECT diagnostic screening questionnaire will enter the open-label titration tapentadol prolonged release (PR) period. In total participants will have 11 planned scheduled visits scheduled over 105 days. At the Enrollment Visit [Day -14 (3 to 14 days prior to the Baseline Visit)] the inclusion and exclusion criteria will be checked to evaluate the participant's eligibility for the trial. Participants on previous analgesics will start a washout period three days up to 2 weeks.The duration of the washout period will depend on previous opioid analgesics and co-analgesics and their respective doses, down-tapering steps. Participants who do not need a washout of previous analgesic treatment (e.g. WHO Step I analgesics), a baseline visit can be scheduled as soon as clinical laboratory monitoring results are available.

At the Baseline Visit (Day 1) participants will start the 3 week open-label titration period tapentadol prolonged release (PR) at doses of 2 x 50 mg per day and will be titrated upwards in steps of 100 mg (2 x 50 mg) on a weekly basis.

Participants who do not qualify for randomization may continue the trial in the open-label continuation arm if they have already reached a satisfactory level of pain relief.

Participants qualifying for randomization in the comparative period (Day 22 to 77) will be allocated to 1 of 2 treatment arms and will continue treatment.

Either they continue on tapentadol prolonged release (PR) with increasing doses of tapentadol PR

• After the randomization visit, participants will titrate up to a total daily dose of 400 mg.
• 1 week after the randomization visit, will titrate up to a total daily dose of 500 mg. Participants in this treatment arm will receive a final dose of 500 mg tapentadol PR per day.

Or start on a combination of tapentadol PR 300 mg per day with pregabalin

• After the randomization visit, participants will continue their previous regimen of tapentadol PR 2 x 150 mg per day plus pregabalin 2 x 75 mg (total daily dose of 150 mg pregabalin).
• 1 week after the randomization visit, participants will continue their previous regimen (end of titration period) of tapentadol PR 2 x 150 mg per day plus pregabalin 2 x 150 mg (total daily dose of 300 mg pregabalin). Participants in this treatment arm will receive a final dose of 300 mg tapentadol PR and 300 mg pregabalin.

Participants in the Comparative Period can be assigned to the open-label pick-up arm and will be treated with a stable dose of tapentadol PR 300 mg per day or 400 mg per day if they experience treatment emergent adverse events (at least possibly related to investigational medicinal product).The open-label pick-up period theoretically starts on Day 29, i.e. one week after the Randomization Visit.

The Final Evaluation (Day 77) is planned to take place 8 weeks after randomization.

After the Final Evaluation a Follow-up Period (blinded tapering down/out of IMP in Week 12 and Follow-up Visit (up to Day 91) will take place. Tapering down/out of medication will be performed according to the Summary of Product Characteristics.

Conditions

Low Back Pain; Neuropathic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tapentadol Prolonged Release

Tapentadol Prolonged Release (100 - 500 mg per day) Oral administration twice daily

Group Type: EXPERIMENTAL

Tapentadol Prolonged Release

Intervention Type: DRUG

100 - 500 mg per day orally twice daily for a maximum of 12 weeks

Tapentadol Prolonged Release open label maintenance

Intervention Type: DRUG

100 - 400 mg per day Tapentadol Prolonged Release orally administered twice daily

Tapentadol Prolonged Release with Pregabalin

Tapentadol Prolonged Release (100 - 300 mg per day) with Pregabalin (150 - 300 mg per day) Both administered orally twice a day.

Group Type: ACTIVE_COMPARATOR

Tapentadol Prolonged Release with Pregabalin

Intervention Type: DRUG

Tapentadol Prolonged Release 100 - 300 mg per day with Pregabalin 150 - 300 mg per day orally twice daily for a maximum of 12 weeks

Tapentadol Prolonged Release open label maintenance

Intervention Type: DRUG

100 - 400 mg per day Tapentadol Prolonged Release orally administered twice daily

Interventions

Tapentadol Prolonged Release

100 - 500 mg per day orally twice daily for a maximum of 12 weeks

Intervention Type: DRUG

Tapentadol Prolonged Release with Pregabalin

Tapentadol Prolonged Release 100 - 300 mg per day with Pregabalin 150 - 300 mg per day orally twice daily for a maximum of 12 weeks

Intervention Type: DRUG

Tapentadol Prolonged Release open label maintenance

100 - 400 mg per day Tapentadol Prolonged Release orally administered twice daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months.
• Subject's pain must require a strong analgesic (defined as World Health Organization (WHO) step III) as judged by the investigator.
• The painDETECT diagnostic screening questionnaire score must be:

• "positive" or
• "unclear".or If the subject is being treated with a stable regimen of centrally acting analgesics (opioids) and/or co-analgesics, even a "negative" painDETECT score (but of at least 9) at the enrollment visit will be acceptable.
• If under regular daily pretreatment with a WHO step II/step III opioid analgesic and/or a centrally acting co-analgesic:

• Subjects must be taking a WHO step II or step III analgesic or co- analgesic on a daily basis for at least 2 weeks prior to the enrollment visit.
• Subjects pretreated with a WHO step II opioid analgesic and/or a centrally acting co-analgesic must have reported an average pain intensity score of at least 5 points (NRS-3≥5) during the last 3 days prior to the enrollment visit. or If under regular, daily pretreatment with a WHO step I analgesic monotherapy or if no regular analgesic pretreatment is reported:
• Subjects must have an average pain intensity score of at least 6 points NRS-3≥6) in the last 3 days prior to the enrollment visit.

Exclusion Criteria

• Presence of concomitant painful conditions other than low back pain that could confound the subject's trial assessments or self-evaluation of the index pain, e.g., syndromes with widespread pain such as fibromyalgia.
• Low back pain caused by cancer and/or metastatic diseases.
• Any painful procedures planned during the trial period (e.g., major surgery) that may, in the opinion of the investigator, affect the effectiveness or safety assessments of the Investigational Medicinal Product (IMP).
• Pending litigation or application for insurance/governmental benefits due to chronic pain or disability and, if granted, benefits might be influenced by a successful participation in the trial.
• Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption, lactose intolerance.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grünenthal GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralf Baron, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Neurological pain research and therapy Clinic for Neurology Campus Kiel, University Clinic Schleswig-Holstein, Schittenhelmstr. 10, 24105 Kiel, Germany

Locations

Site 506

Klagenfurt, , Austria

Site 503

Senftenberg, , Austria

Site 501

Vienna, , Austria

Site 502

Vienna, , Austria

Site 504

Vienna, , Austria

Site 505

Vienna, , Austria

Site 605

Dour, , Belgium

Site 602

Genk, , Belgium

Site 603

Gozée, , Belgium

Site 604

Ham, , Belgium

Site 601

Pellenberg, , Belgium

Site 702

Copenhagen, , Denmark

Site 704

Frederiksberg, , Denmark

Site 701

Glostrup Municipality, , Denmark

Site 703

Ringsted, , Denmark

DE 118

Berlin, , Germany

Site 107

Berlin, , Germany

Site 111

Böhlen, , Germany

Site 105

Cologne, , Germany

Site 116

Cologne, , Germany

Site 115

Cottbus, , Germany

Site 103

Hamburg, , Germany

Site 110

Hamburg, , Germany

Site 101

Kiel, , Germany

Site 114

Kiel, , Germany

Site 113

Leipzig, , Germany

Site 109

Lübeck, , Germany

Site 106

Rendsburg, , Germany

Site 108

Schönau, , Germany

Site 117

Weimar, , Germany

Site 112

Westerstede, , Germany

Site 104

Wiesbaden, , Germany

Site 803

Amsterdam, , Netherlands

Site 804

Eindhoven, , Netherlands

Site 805

Enschede, , Netherlands

Site 802

Heerenveen, , Netherlands

Site 801

Sliedrecht, , Netherlands

Site 309

Bydgoszcz, , Poland

Site 312

Gdansk, , Poland

Site 303

Katowice, , Poland

Site 308

Krakow, , Poland

Site 310

Krakow, , Poland

Site 311

Krakow, , Poland

Site 307

Lublin, , Poland

Site 306

Ostrów Mazowiecka, , Poland

Site 304

Poznan, , Poland

Site 301

Warsaw, , Poland

Site 302

Warsaw, , Poland

Site 305

Wroclaw, , Poland

Site 904

A Coruña, , Spain

Site 908

Alicante, , Spain

Site 901

Badalona, , Spain

Site 905

Barcelona, , Spain

Site 902

Centelles, , Spain

Site 907

Granada, , Spain

Site 909

Madrid, , Spain

Site 910

Madrid, , Spain

Site 903

Oviedo, , Spain

Site 911

Valencia, , Spain

Countries

Austria; Belgium; Denmark; Germany; Netherlands; Poland; Spain

References

Baron R, Martin-Mola E, Muller M, Dubois C, Falke D, Steigerwald I. Effectiveness and Safety of Tapentadol Prolonged Release (PR) Versus a Combination of Tapentadol PR and Pregabalin for the Management of Severe, Chronic Low Back Pain With a Neuropathic Component: A Randomized, Double-blind, Phase 3b Study. Pain Pract. 2015 Jun;15(5):455-70. doi: 10.1111/papr.12200. Epub 2014 Apr 17.

Reference Type: RESULT

PMID: 24738609 (View on PubMed)

Baron R, Kern U, Muller M, Dubois C, Falke D, Steigerwald I. Effectiveness and Tolerability of a Moderate Dose of Tapentadol Prolonged Release for Managing Severe, Chronic Low Back Pain with a Neuropathic Component: An Open-label Continuation Arm of a Randomized Phase 3b Study. Pain Pract. 2015 Jun;15(5):471-86. doi: 10.1111/papr.12199. Epub 2014 Apr 18.

Reference Type: RESULT

PMID: 24750558 (View on PubMed)

Other Identifiers

2010-019998-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KF5503/58

Identifier Type: OTHER

Identifier Source: secondary_id

247251

Identifier Type: -

Identifier Source: org_study_id