Low Back PainPhase 4NCT01352741
Comparison of Increasing Doses of Tapentadol Versus a Combination of Tapentadol and Pregabalin
A Phase 4 study testing Tapentadol Prolonged Release, Tapentadol Prolonged Release with Pregabalin and Tapentadol Prolonged Release open label maintenance in people with Low Back Pain and Neuropathic Pain, run by Grünenthal GmbH at 59 sites in 7 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Low Back Pain, Neuropathic Pain
- What is being tested?
- Tapentadol Prolonged Release, Tapentadol Prolonged Release with Pregabalin and Tapentadol Prolonged Release open label maintenance
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 622 participants
- Where
- 59 sitesin 7 countries
- Study dates
- Mar 2011to Jan 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
Trial locations and contacts
59 sites in 7 countries.
59 sites in 7 countries
Germany17 sites
DE 118
Berlin, 10787
Site 107
Berlin
Site 111
Böhlen
Site 105
Cologne
Site 116
Cologne
Site 115
Cottbus
Site 103
Hamburg
Site 110
Hamburg
Site 101
Kiel
Site 114
Kiel
Site 113
Leipzig
Site 109
Lübeck
Site 106
Rendsburg
Site 108
Schönau
Site 117
Weimar
Site 112
Westerstede
Site 104
Wiesbaden
Poland12 sites
Site 309
Bydgoszcz
Site 312
Gdansk
Site 303
Katowice
Site 308
Krakow
Site 310
Krakow
Site 311
Krakow
Site 307
Lublin
Site 306
Ostrów Mazowiecka
Site 304
Poznan
Site 301
Warsaw
Site 302
Warsaw
Site 305
Wroclaw
Spain10 sites
Site 904
A Coruña
Site 908
Alicante
Site 901
Badalona
Site 905
Barcelona
Site 902
Centelles
Site 907
Granada
Site 909
Madrid
Site 910
Madrid
Site 903
Oviedo
Site 911
Valencia
Austria6 sites
Site 506
Klagenfurt
Site 503
Senftenberg
Site 501
Vienna
Site 502
Vienna
Site 504
Vienna
Site 505
Vienna
Belgium5 sites
Site 605
Dour
Site 602
Genk
Site 603
Gozée
Site 604
Ham
Site 601
Pellenberg
Netherlands5 sites
Site 803
Amsterdam
Site 804
Eindhoven
Site 805
Enschede
Site 802
Heerenveen
Site 801
Sliedrecht
Denmark4 sites
Site 702
Copenhagen
Site 704
Frederiksberg
Site 701
Glostrup Municipality
Site 703
Ringsted
About this study
Official title: Evaluation of the Effectiveness, Safety, and Tolerability of Tapentadol PR Versus a Combination of Tapentadol PR and Pregabalin in Subjects With Severe Chronic Low Back Pain With a Neuropathic Pain Component
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.
Read the 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
- Being tested
- Tapentadol Prolonged Release, Tapentadol Prolonged Release with Pregabalin, Tapentadol Prolonged Release open label maintenance
- Keywords
- low back pain, neuropathic, pain assessment, centrally acting tapentadol pregabalin, severe chronic
- Medical subject headings
- Low Back Pain, Neuralgia, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tapentadol Prolonged ReleaseDrug
100 - 500 mg per day orally twice daily for a maximum of 12 weeks
Tapentadol Prolonged Release with PregabalinDrug
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 maintenanceDrug
100 - 400 mg per day Tapentadol Prolonged Release orally administered twice daily
| Study group | Role | What they receive |
|---|---|---|
| Tapentadol Prolonged Release | Experimental | Tapentadol Prolonged Release (100 - 500 mg per day) Oral administration twice daily Receives: 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. Receives: Drug: Tapentadol Prolonged Release with Pregabalin; Drug: Tapentadol Prolonged Release open label maintenance |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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)
The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine. This is the treatment period prior to the primary outcome period.
Measured: 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)
The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine.
Measured: 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)
The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine.
Measured: Final Evaluation Visit (Day 77)
Open-label Titration Period: Radiating Pain
The NRS-3 pain intensity score at the visits in the open-label titration period for the two comparative double-blind period treatment groups analyzed is reported. NRS-3 pain intensity score (recalled average pain intensity score during the last 3 days on an 11-point NRS) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot) is reported. Where 0 = no pain and 10 indicates pain as bad as you can imagine.
Measured: 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
The NRS-3 pain intensity score at the visits in the open-label titration period for the two comparative double-blind period treatment groups analyzed is reported. NRS-3 pain intensity score (recalled average pain intensity score during the last 3 days on an 11-point NRS) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot) is reported. Where 0 = no pain and 10 indicates pain as bad as you can imagine.
Measured: Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in NRS-3 Pain Intensity Score for the Radiating Pain
NRS-3 pain intensity score (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) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot).
The value reported represents the change from the randomization visit (i.e., the last 3 days in the titration period) to the end of the double-blind comparative period (i.e., the last 3 days in the comparative period). The theoretical values range from -10 to 10. A negative sign indicates a decrease in pain from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (baseline visit).
Measured: Randomization Visit (Day 22); End of Evaluation Visit (Day 77)
Open-label Titration Period: Worst Mean Pain Intensity Scores Over the Past 24 Hours
The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine.
The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit".
Measured: Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Comparative Double-blind Period Population Worst Mean Pain Intensity Scores Over the Past 24 Hours
The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric Rating Scale (NRS), where 0 = "no pain" and 10 = "pain as bad as you can imagine".
The participant was asked : "Please rate your pain intensity by assessing the one number that best describes your worst pain during the past 24 hours prior to the visit".
Measured: Enrollment Visit (Day-12); Baseline Visit (day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in Worst Pain Intensity Over the Past 24 Hours
The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine.
The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit".
A negative change indicates that the pain intensity decreased from the start of the trial.
Measured: Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: painDETECT Assessments
The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear".
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Comparative Double-blind Period Population painDETECT Assessment
The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear".
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in painDETECT Final Assessment
The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear". The theoretical range of change in this trial ranged from -38 to 19. A negative change indicated a decrease in their neuropathic component of pain.
Measured: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment
In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale; from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 100.
Measured: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment in the Double-blind Comparative Period Population
In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale; from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 100.
Measured: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment
In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale, from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. Spontaneous Pressing Pain Subscore). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) subscores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 10 (100 for the overall score) . A negative change indicates that the intensity of the symptom has decreased since the start of treatment.
Measured: Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Physical Health Composite Score (PCS)
The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical and mental summary scores were calculated from the individual responses. A higher score indicates a better perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state.
Measured: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Changes in the Short Form Health Survey (SF-12) Physical Health Composite Score (PCS)
The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical summary scores were calculated from the individual responses to those questions covering physical health. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state.
The change in the SF-12 score shows an improvement in health from baseline if the values are positive. The higher the value the greater the improvement.
Measured: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Mental Health Composite Score (MCS)
The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The mental health summary scores were calculated from the individual responses to two of the 12 questions. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible mental health.
Measured: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in Short Form Health Survey (SF-12) Mental Health Composite Score (MCS)
The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The mental health summary scores were calculated from the individual responses to two of the 12 questions. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible mental health.
Measured: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: EuroQol-5 Dimension (EQ-5D) Health Status Index Score for the Double-blind Comparative Period Population
The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating "full health" and 0 representing "dead"). The higher the values (the closer the value is to 1) the better the health status in a treatment group.
Measured: Enrollment Visit (day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change EuroQol-5 Dimension (EQ-5D) Health Status Index
The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating "full health" and 0 representing "dead"). The higher the values (the closer the value is to 1) the better the health status in a treatment group.
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Patient Global Impression of Change (PGIC)
In the Patient Global Impression of Change (PGIC) the participant indicated the perceived change over the treatment period. PGIC is a 7 point scale where the patient's rates overall improvement. Patients rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."
Measured: Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC)
In the Clinician Global Impression of Change (CGIC) the clinician indicated the perceived change over the treatment period. The clinician was requested to choose one of seven categories for each participant. The Clinician rated the participants change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."
Measured: Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Open-label Titration Period: Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety.
A decrease in values over the trial period indicate that there has been an improvement.
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety.
A negative sign indicates that there has been a decrease in anxiety since the start of treatment.
Measured: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement.
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement. A negative change value indicates a decrease in the depression score since the start of treatment.
Measured: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Sleep Evaluation Questionnaire - Latency
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the sleep latency.
To assess latency the participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]?
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Sleep Evaluation Questionnaire - Latency in the Double-blind Comparative Period Population
The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]? The values are for the night prior to the Randomization Visit (Baseline) and for the night prior to the Final Evaluation Visit (12 weeks after randomization). The higher the value the longer it took to fall asleep. Sleep evaluation questionnaire (SQ) items
Measured: Enrollment Visit (Day -12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period Sleep Evaluation Questionnaire: Change in Latency
The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]? The values are for the night prior to the visits. The negative change from baseline indicates that the time to falling asleep decreased from baseline in a treatment group.
Measured: Baseline Visit (Day 1); Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Awakenings
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.
How many times did you wake up during the night? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Randomization Visit (Day 22).
The participant was asked at each visit: "How many times did you wake up during the night?"
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Sleep Evaluation - Number of Awakenings in the Double-blind Comparative Period Population
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.
How many times did you wake up during the night? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Randomization Visit (Day 22).
The participant was asked at each visit: "How many times did you wake up during the night?"
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in the Number of Awakenings
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings. Participants were asked: How many times did you wake up during the night? The change in the Number of Awakenings was calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Final Evaluation Visit (Day 77). A negative change indicates that the number of awakenings in a treatment group have gone down since the Baseline or Randomization Visit. In general pain can interfere with sleep, one potential indicator is the number of awakenings.
Measured: Baseline Visit (Day 1); Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Open-label Titration Period: Sleep Evaluation Questionnaire - Time Slept
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.
The participant was asked: "How long did you sleep last night?" [Answered in hours and minutes].
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Hours Slept in the Double-blind Comparative Period Population
The participants were requested to answer the following question:
How long did you sleep last night [hours]? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline) and for the night prior to the End of the Continuation Visit (12 weeks after randomization).
Measured: Enrollment Visit (Day -12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Sleep Evaluation Questionnaire - Change in the Number of Hours Slept
The sleep evaluation questionnaire was completed by the participant. The answer was in response to the question: Sleep evaluation: How long did you sleep last night [hours]? The value reported is the change in the number of hours of sleep from baseline. The positive value indicates that there was an increase in the number of hours of sleep in a treatment group.
Measured: Baseline Visit (Day -12); Randomization Visit (Day 1); Final Evaluation Visit (Day 77)
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.
The participant rated this categorically as being one of the following: excellent, good, fair or poor.
Measured: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.
The participant rated this categorically as being one of the following: excellent, good, fair or poor.
Measured: Enrollment Visit (Day-12)
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.
The participant rated this categorically as being one of the following: excellent, good, fair or poor.
Measured: Baseline Visit (Day 1)
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.
The participant rated this categorically as being one of the following: excellent, good, fair or poor.
Measured: Randomization Visit (Day 22)
Double-blind Comparative Period: Change in the Overall Quality of Sleep
The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.
The improvement, no change or worsening is reported based on the replies scored by the participants given at their End of Continuation Visit.
Measured: Randomization Visit (Day 22) to Final Evaluation (Day 77)
Open-label Titration Period: Subject's Satisfaction With Treatment
Participants rated their satisfaction with the study drug (IMPs) by answering the following question on a 5-point rating scale:
"How would you rate your overall satisfaction with your current pain treatment?": Excellent, Very Good, Good, Fair and Poor.
Measured: End of Open-label Titration Period at Randomization Visit (Day 22)
Double-blind Comparative Period: Subject's Satisfaction With Treatment
Participants rated their satisfaction with the study drug (IMPs) by answering the following question on a 5-point rating scale:
"How would you rate your overall satisfaction with your current pain treatment?": Excellent, Very Good, Good, Fair and Poor.
Measured: End of Comparative Period at Final Evaluation Visit (Day 77)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2011 (estimated)
- Study startMar 2011
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Low Back PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 622 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grünenthal GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ralf Baron, Prof. Dr., Principal investigator, Neurological pain research and therapy Clinic for Neurology Campus Kiel, University Clinic Schleswig-Holstein, Schittenhelmstr. 10, 24105 Kiel, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01352741
- Sponsor's protocol ID
- 247251
- Other IDs
- 2010-019998-14, KF5503/58
- Status last verified
- Oct 2019
- First submitted
- 12 Apr 2011
- Last updated
- 28 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24738609Baron 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.
PubMed 24750558
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effectiveness, Safety, and Tolerability of Tapentadol PR Versus a Combination of Tapentadol PR and Pregabalin in Subjects With Severe Chronic Low Back Pain With a Neuropathic Pain Component
- ClinicalTrials.gov ID
- NCT01352741
- Acronym / sponsor ID
- 247251
- Conditions
- Low Back Pain, Neuropathic Pain
- Keywords
- low back pain, neuropathic, pain assessment, centrally acting tapentadol pregabalin, severe chronic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 622 participants (actual)
- Lead sponsor
- Grünenthal GmbHIndustry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 12 May 2011 (estimated)
- Results
- Posted 12 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tapentadol Prolonged Release | Experimental | Drug: Tapentadol Prolonged Release, Drug: Tapentadol Prolonged Release open label maintenanceTapentadol Prolonged Release (100 - 500 mg per day) Oral administration twice daily |
| Tapentadol Prolonged Release with Pregabalin | Active comparator | Drug: Tapentadol Prolonged Release with Pregabalin, Drug: Tapentadol Prolonged Release open label maintenanceTapentadol Prolonged Release (100 - 300 mg per day) with Pregabalin (150 - 300 mg per day) Both administered orally twice a day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- If under regular daily pretreatment with a WHO step II/step III opioid analgesic and/or a centrally acting co-analgesic:
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tapentadol Prolonged Release100 - 500 mg per day orally twice daily for a maximum of 12 weeks | Drug | Tapentadol Prolonged Release |
| Tapentadol Prolonged Release with PregabalinTapentadol Prolonged Release 100 - 300 mg per day with Pregabalin 150 - 300 mg per day orally twice daily for a maximum of 12 weeks | Drug | Tapentadol Prolonged Release with Pregabalin |
| Tapentadol Prolonged Release open label maintenance100 - 400 mg per day Tapentadol Prolonged Release orally administered twice daily | Drug | Tapentadol Prolonged Release, Tapentadol Prolonged Release with Pregabalin |
Primary outcome
Change in the Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)
Time frame: Randomization (Day 22); Final Evaluation Visit (Day 77)
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).
43 secondary outcomes
Open-label Titration Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)
Time frame: 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)
Time frame: 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)
Time frame: Final Evaluation Visit (Day 77)
Open-label Titration Period: Radiating Pain
Time frame: 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
Time frame: Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in NRS-3 Pain Intensity Score for the Radiating Pain
Time frame: Randomization Visit (Day 22); End of Evaluation Visit (Day 77)
Open-label Titration Period: Worst Mean Pain Intensity Scores Over the Past 24 Hours
Time frame: Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Comparative Double-blind Period Population Worst Mean Pain Intensity Scores Over the Past 24 Hours
Time frame: Enrollment Visit (Day-12); Baseline Visit (day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in Worst Pain Intensity Over the Past 24 Hours
Time frame: Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: painDETECT Assessments
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Comparative Double-blind Period Population painDETECT Assessment
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in painDETECT Final Assessment
Time frame: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment
Time frame: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment in the Double-blind Comparative Period Population
Time frame: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment
Time frame: Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Physical Health Composite Score (PCS)
Time frame: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Changes in the Short Form Health Survey (SF-12) Physical Health Composite Score (PCS)
Time frame: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Mental Health Composite Score (MCS)
Time frame: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in Short Form Health Survey (SF-12) Mental Health Composite Score (MCS)
Time frame: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: EuroQol-5 Dimension (EQ-5D) Health Status Index Score for the Double-blind Comparative Period Population
Time frame: Enrollment Visit (day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change EuroQol-5 Dimension (EQ-5D) Health Status Index
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Patient Global Impression of Change (PGIC)
Time frame: Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC)
Time frame: Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Open-label Titration Period: Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population
Time frame: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population
Time frame: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)
Open-label Titration Period: Sleep Evaluation Questionnaire - Latency
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Sleep Evaluation Questionnaire - Latency in the Double-blind Comparative Period Population
Time frame: Enrollment Visit (Day -12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period Sleep Evaluation Questionnaire: Change in Latency
Time frame: Baseline Visit (Day 1); Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Awakenings
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Sleep Evaluation - Number of Awakenings in the Double-blind Comparative Period Population
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Change in the Number of Awakenings
Time frame: Baseline Visit (Day 1); Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)
Open-label Titration Period: Sleep Evaluation Questionnaire - Time Slept
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Hours Slept in the Double-blind Comparative Period Population
Time frame: Enrollment Visit (Day -12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Double-blind Comparative Period: Sleep Evaluation Questionnaire - Change in the Number of Hours Slept
Time frame: Baseline Visit (Day -12); Randomization Visit (Day 1); Final Evaluation Visit (Day 77)
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep
Time frame: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
Time frame: Enrollment Visit (Day-12)
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
Time frame: Baseline Visit (Day 1)
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population
Time frame: Randomization Visit (Day 22)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24738609Baron 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.
- Results publication: PubMed 24750558Baron 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ralf Baron, Prof. Dr. principal investigator
Neurological pain research and therapy Clinic for Neurology Campus Kiel, University Clinic Schleswig-Holstein, Schittenhelmstr. 10, 24105 Kiel, Germany
59 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tapentadol Prolonged Release, Tapentadol Prolonged Release with Pregabalin and Tapentadol Prolonged Release open label maintenance in people with Low Back Pain and Neuropathic Pain, run by Grünenthal GmbH at 59 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 59 sites in Germany, Poland, Spain, Austria, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) (time frame: Randomization (Day 22); Final Evaluation Visit (Day 77)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01352741, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2019.