Phase 4
Completed N=445
Comparison of Increasing Doses of Tapentadol Versus a Combination of Tapentadol and Pregabalin
Source: ClinicalTrials.gov NCT01352741 ↗Enrolled (actual)
445
Serious AEs
1.8%
Results posted
Aug 2016
Primary outcomePrimary: Change in the Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) — -1.6; -1.7 units on a scale
◆ Published Evidence
Established
71citations · ~6 / year
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.
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.
Linked Publications (2)
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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.
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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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in the Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) |
-1.6; -1.7 | — |
| SECONDARY Open-label Titration Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) |
7.2; 8.3; 5.4 | — |
| SECONDARY Open-label Continuation Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) |
7.3; 7.9; 2.6; 2.6 | — |
| SECONDARY 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) |
4.4; 4.5 | — |
| SECONDARY Open-label Titration Period: Radiating Pain |
7.0; 8.0; 5.3 | — |
| SECONDARY Open-label Titration Period: Radiating Mean Pain Intensity Score for the Comparative Period Population |
7.1; 6.9; 8.1; 8.1; 5.6; 5.7 | — |
| SECONDARY Double-blind Comparative Period: Change in NRS-3 Pain Intensity Score for the Radiating Pain |
-1.5; -1.9 | — |
| SECONDARY Open-label Titration Period: Worst Mean Pain Intensity Scores Over the Past 24 Hours |
7.6; 8.5; 5.8 | — |
| SECONDARY Open-label Titration Period: Comparative Double-blind Period Population Worst Mean Pain Intensity Scores Over the Past 24 Hours |
7.8; 7.5; 8.5; 8.7; 6.3; 6.4 | — |
| SECONDARY Double-blind Comparative Period: Change in Worst Pain Intensity Over the Past 24 Hours |
-1.7; -1.8 | — |
| SECONDARY Open-label Titration Period: painDETECT Assessments |
21.4; 22.7; 16.9 | — |
| SECONDARY Open-label Titration Period: Comparative Double-blind Period Population painDETECT Assessment |
21.6; 21.7; 22.4; 23.8; 17.6; 18.4 | — |
| SECONDARY Double-blind Comparative Period: Change in painDETECT Final Assessment |
-10.2; -11.0; -6.0; -5.9 | — |
| SECONDARY Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment |
55.2; 62.7; 42.0 | — |
| SECONDARY Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment in the Double-blind Comparative Period Population |
54.8; 57.6; 62.8; 65.4; 45.2; 46.5 | — |
| SECONDARY Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment |
-16.8; -16.6; -1.9; -2.3; -1.4; -1.4 | — |
| SECONDARY Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Physical Health Composite Score (PCS) |
29.9; 29.8; 28.2; 28.5; 34.1; 34.1 | — |
| SECONDARY Double-blind Comparative Period: Changes in the Short Form Health Survey (SF-12) Physical Health Composite Score (PCS) |
12.3; 11.1; 6.2; 5.6 | — |
| SECONDARY Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Mental Health Composite Score (MCS) |
46.1; 44.8; 45.4; 43.2; 49.2; 47.3 | — |
| SECONDARY Double-blind Comparative Period: Change in Short Form Health Survey (SF-12) Mental Health Composite Score (MCS) |
3.9; 6.5; 0.1; 2.5 | — |
| SECONDARY Open-label Titration Period: EuroQol-5 Dimension (EQ-5D) Health Status Index Score for the Double-blind Comparative Period Population |
0.32; 0.33; 0.29; 0.18; 0.55; 0.52 | — |
| SECONDARY Double-blind Comparative Period: Change EuroQol-5 Dimension (EQ-5D) Health Status Index |
0.34; 0.43; 0.09; 0.09 | — |
| SECONDARY Double-blind Comparative Period: Patient Global Impression of Change (PGIC) |
28; 32; 44; 66; 51; 31 | — |
| SECONDARY Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) |
26; 30; 54; 82; 46; 19 | — |
| SECONDARY Open-label Titration Period: Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population |
7.4; 8.6; 7.7; 9.0; 5.8; 7.1 | — |
| SECONDARY Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population |
-2.2; -3.1; -0.3; -1.2 | — |
| SECONDARY Open-label Titration Period: Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population |
6.9; 7.8; 7.6; 8.6; 6.0; 6.8 | — |
| SECONDARY Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population |
-2.0; -3.1; -0.4; -1.3 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Latency |
1.2; 1.5; 1.3 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Latency in the Double-blind Comparative Period Population |
1.3; 1.3; 1.5; 1.5; 1.1; 1.4 | — |
| SECONDARY Double-blind Comparative Period Sleep Evaluation Questionnaire: Change in Latency |
-0.3; -0.3; 0.2; -0.2 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Awakenings |
3.3; 3.9; 2.5 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation - Number of Awakenings in the Double-blind Comparative Period Population |
3.2; 3.4; 3.6; 4.6; 2.5; 2.7 | — |
| SECONDARY Double-blind Comparative Period: Change in the Number of Awakenings |
-1.4; -2.5; -0.2; -0.8 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Time Slept |
5.8; 5.3; 6.4 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Hours Slept in the Double-blind Comparative Period Population |
5.8; 5.7; 5.3; 5.2; 6.2; 6.4 | — |
| SECONDARY Double-blind Comparative Period: Sleep Evaluation Questionnaire - Change in the Number of Hours Slept |
1.2; 1.6; 0.3; 0.3 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep |
9; 5; 21; 110; 76; 173 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population |
7; 8; 62; 59; 48; 56 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population |
7; 8; 62; 59; 48; 56 | — |
| SECONDARY Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population |
7; 8; 62; 59; 48; 56 | — |
| SECONDARY Double-blind Comparative Period: Change in the Overall Quality of Sleep |
39; 58; 63; 59; 21; 20 | — |
| SECONDARY Open-label Titration Period: Subject's Satisfaction With Treatment |
12; 119; 178; 58; 11; 67 | — |
| SECONDARY Double-blind Comparative Period: Subject's Satisfaction With Treatment |
3; 6; 32; 28; 43; 43 | — |
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.
Data sourced from ClinicalTrials.gov (NCT01352741) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.