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

NCT01352741 | Completed Phase 4 Results

• 3 other identifiers: 2472512010-019998-14KF5503/58
• Study Type: interventional
• Target: 622
• Locations: 7 countries
• Sites: 59

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.

Conditions

Low Back Pain; Neuropathic Pain

Keywords

low back pain; neuropathic; pain assessment; centrally acting tapentadol pregabalin; severe chronic

Outcome Measures

Primary Outcomes (1)

• Change in the Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)

  The primary endpoint is defined as the comparison of tapentadol prolonged release (PR) 300 mg plus 200 mg per day and the combination of tapentadol PR 300 mg per day and pregabalin 300 mg per day regarding the change in NRS-3 pain intensity scores (recalled average pain intensity score during the last 3 days on 11-point NRS, where 0 is the no pain and 10 is pain as bad as you can imagine) from the randomization visit to the final evaluation visit. Theoretically a maximum decrease of -10 and an increase of +4 in the pain intensity would have been possible. A negative sign indicates a decrease in pain intensity from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (Baseline visit).

  Randomization (Day 22); Final Evaluation Visit (Day 77)

Secondary Outcomes (43)

• Open-label Titration Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)

  Enrollment (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)

• Open-label Continuation Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)

  Enrollment (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

• End of Open-label Pick-up Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)

  Final Evaluation Visit (Day 77)

• Open-label Titration Period: Radiating Pain

  Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)

• Open-label Titration Period: Radiating Mean Pain Intensity Score for the Comparative Period Population

  Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)

Study Arms (2)

Tapentadol Prolonged Release

EXPERIMENTAL

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

Drug: Tapentadol Prolonged Release; Drug: Tapentadol Prolonged Release open label maintenance

Tapentadol Prolonged Release with Pregabalin

ACTIVE COMPARATOR

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

Drug: Tapentadol Prolonged Release with Pregabalin; Drug: Tapentadol Prolonged Release open label maintenance

Interventions

Tapentadol Prolonged Release DRUG

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

Tapentadol Prolonged Release

Tapentadol Prolonged Release with Pregabalin 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 with Pregabalin

Tapentadol Prolonged Release open label maintenance DRUG

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

Tapentadol Prolonged Release; Tapentadol Prolonged Release with Pregabalin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (59)

Site 506

Klagenfurt, Austria

Location

Site 503

Senftenberg, Austria

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Site 501

Vienna, Austria

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Site 502

Vienna, Austria

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Site 504

Vienna, Austria

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Site 505

Vienna, Austria

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Site 605

Dour, Belgium

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Site 602

Genk, Belgium

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Site 603

Gozée, Belgium

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Site 604

Ham, Belgium

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Site 601

Pellenberg, Belgium

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Site 702

Copenhagen, Denmark

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Site 704

Frederiksberg, Denmark

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Site 701

Glostrup Municipality, Denmark

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Site 703

Ringsted, Denmark

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DE 118

Berlin, 10787, Germany

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Site 107

Berlin, Germany

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Site 111

Böhlen, Germany

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Site 105

Cologne, Germany

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Site 116

Cologne, Germany

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Site 115

Cottbus, Germany

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Site 103

Hamburg, Germany

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Site 110

Hamburg, Germany

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Site 101

Kiel, Germany

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Site 114

Kiel, Germany

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Site 113

Leipzig, Germany

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Site 109

Lübeck, Germany

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Site 106

Rendsburg, Germany

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Site 108

Schönau, Germany

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Site 117

Weimar, Germany

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Site 112

Westerstede, Germany

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Site 104

Wiesbaden, Germany

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Site 803

Amsterdam, Netherlands

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Site 804

Eindhoven, Netherlands

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Site 805

Enschede, Netherlands

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Site 802

Heerenveen, Netherlands

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Site 801

Sliedrecht, Netherlands

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Site 309

Bydgoszcz, Poland

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Site 312

Gdansk, Poland

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Site 303

Katowice, Poland

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Site 308

Krakow, Poland

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Site 310

Krakow, Poland

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Site 311

Krakow, Poland

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Site 307

Lublin, Poland

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Site 306

Ostrów Mazowiecka, Poland

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Site 304

Poznan, Poland

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Site 301

Warsaw, Poland

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Site 302

Warsaw, Poland

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Site 305

Wroclaw, Poland

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Site 904

A Coruña, Spain

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Site 908

Alicante, Spain

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Site 901

Badalona, Spain

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Site 905

Barcelona, Spain

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Site 902

Centelles, Spain

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Site 907

Granada, Spain

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Site 909

Madrid, Spain

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Site 910

Madrid, Spain

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Site 903

Oviedo, Spain

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Site 911

Valencia, Spain

Location

Related Publications (2)

• 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.

  PMID: 24738609 RESULT

• 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.

  PMID: 24750558 RESULT

MeSH Terms

Conditions

Low Back Pain; Neuralgia; Bronchiolitis Obliterans Syndrome

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Grünenthal GmbH

+49 241 569 3223

Study Officials

• Ralf Baron, Prof. Dr.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2011
• First Posted: May 12, 2011
• Study Start: March 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: October 28, 2019
• Results First Posted: August 12, 2016

Record last verified: 2019-10

Locations

AU (6); DK (4); NL (5); BE (5); PL (12); DE (17); ES (10)