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PainPhase 3NCT00986258

Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Chronic Low Back Pain Taking WHO Step III Analgesics But Showing a Lack of Tolerability

A Phase 3 study testing Tapentadol Prolonged Release in people with Pain and Chronic Pain, run by Grünenthal GmbH at 27 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The main objective of the study is to evaluate the effectiveness, tolerability, and safety of tapentadol hydrochloride prolonged release in subjects suffering from severe chronic low back pain (LBP) who are taking WHO Step III analgesics and show lack of tolerability. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pain, Chronic Pain, Low Back Pain
What is being tested?
Tapentadol Prolonged Release
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
27 sitesin 8 countries
Study dates
30 Oct 2009to Jan 2011
Phase
Phase 3
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

  • Participants must have signed an Informed Consent Form indicating that they understand the purpose of and procedures required for the trial and are willing to participate in it.
  • Participants are men or non-pregnant, non-lactating women. Sexually active women must be postmenopausal, surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, male partner sterilization) before entry and throughout the trial. Women of childbearing potential must have a negative pregnancy test at screening.
  • Participants must be appropriately communicative to verbalize and to differentiate with regard to location and intensity of the pain.
  • Participants must be at least 18 years of age.
  • Participants must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months
  • If the Participant has radicular pain, this must have been present for at least 3 months and stable for the 4 weeks before enrollment.
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  • Participant's pain must require a strong analgesic (defined as WHO Step III) as judged by the Investigator.
  • Participants must be taking a WHO Step III analgesic on a daily basis for at least 3 months prior to the Screening Visit.
  • Participants must have responded to the WHO Step III analgesic, i.e., participants must have a confirmed average pain intensity score (NRS 3) of ≤5 points during the last 3 days prior to the Screening Visit.
  • Participants must report opioid-related side effects as the reason to change their analgesic.
  • Participants must report a rate of satisfaction with their previous analgesic regimen not exceeding "fair" on a subject satisfaction with treatment scale (5-point VRS).

Who cannot join

  • Presence of a clinically significant disease or laboratory findings that in the Investigator's opinion may affect efficacy or safety assessments.
  • Presence of active systemic or local infection that may, in the opinion of the Investigator, affect the efficacy, quality of life/function or safety assessments.
  • History of alcohol or drug abuse, or suspicion of in Investigator's judgement.
  • Presence of concomitant autoimmune inflammatory conditions.
  • Known history of or laboratory values reflecting severe renal impairment.
  • Known history of moderately or severely impaired hepatic function.
Show all 21Show fewer
  • History of or active hepatitis B or C within the past 3 months or history of HIV infection.
  • History of seizure disorder or epilepsy.
  • Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm. Severe traumatic brain injury within 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or post traumatic amnesia lasting more than 24 h) or residual sequelae suggesting transient changes in consciousness.
  • Pregnant or breast-feeding.
  • History of allergy to, or hypersensitivity to tapentadol hydrochloride or its excipients, or contraindications related to tapentadol hydrochloride including:
  • Subjects with acute or severe bronchial asthma or hypercapnia.
  • Subjects who have or are suspected of having paralytic ileus.
  • Employees of the Investigator or trial site, with direct involvement in this trial or other trials under the direction of the Investigator or trial site, as well as family members of employees of the Investigator.
  • Participation in another trial concurrently or within 4 weeks prior to the Screening Visit.
  • Known to or suspected of not being able to comply with the protocol and the use of the investigational medicinal product.
  • Use of monoamine oxidase inhibitors within 14 days before the Screening Visit.
  • Non-stable dosing of selective serotonin reuptake inhibitors within 30 days before the Screening Visit (the doses must remain stable during the trial).
  • Presence of concomitant painful condition other than low back pain that could confound the subject's trial assessments or self evaluation of pain, e.g., anatomical deformities, significant skin conditions such as abscess or syndromes with widespread pain such as fibromyalgia.
  • Any painful procedures during the trial (e.g., major surgery) that may, in the opinion of the Investigator, affect the efficacy or safety assessments.
  • Pending litigation due to chronic pain or disability.

Trial locations and contacts

27 sites in 8 countries.

27 sites in 8 countries

Germany7 sites

  • DE005

    Albstadt

  • DE001

    Berlin

  • DE003

    Berlin

  • DE006

    Kiel

  • DE004

    Leipzig

  • DE008

    Leipzig

  • DE007

    Stuttgart

Other trials in Germany

Spain5 sites

  • ES006

    Cadiz

  • ES001

    Granada

  • ES003

    Málaga

  • ES004

    Seville

  • ES005

    Valencia

Other trials in Spain

Belgium4 sites

  • BE004

    Bruges

  • BE003

    Charleroi

  • BE002

    Edegem

  • BE001

    Liège

Other trials in Belgium

Netherlands4 sites

  • NL002

    Alkmaar

  • NL004

    Doetinchem

  • NL003

    Eindhoven

  • NL001

    Tiel

Other trials in Netherlands

France2 sites

  • FR004

    Thionville

  • FR001

    Toulouse

Other trials in France

Poland2 sites

  • PL002

    Krakow

  • PL001

    Poznan

Other trials in Poland

Switzerland2 sites

  • CH001

    Basel

  • CH002

    Sankt Gallen

Other trials in Switzerland

Czechia1 site

  • CZ001

    Brno

Other trials in Czechia

About this study

Official title: An Evaluation of the Effectiveness and Tolerability of Tapentadol Hydrochloride Prolonged Release, and Tapentadol Hydrochloride Immediate Release on Demand, in Subjects With Severe Chronic Nociceptive, Mixed or Neuropathic Low Back Pain Taking WHO Step III Analgesics But Showing a Lack of Tolerability

The main objective of the study is to evaluate the effectiveness, tolerability, and safety of tapentadol hydrochloride prolonged release in subjects suffering from severe chronic low back pain (LBP) who are taking WHO Step III analgesics and show lack of tolerability. 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 outcome.

The trial will compare the effectiveness of previous analgesic treatment (WHO Step III) with that of tapentadol hydrochloride prolonged release treatment during defined periods of evaluation.

Being tested
Tapentadol Prolonged Release
Keywords
pain assessment, tapentadol, centrally acting analgesic
Medical subject headings
Pain, Chronic Pain, Low Back Pain, Neuralgia, Nociceptive Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tapentadol Prolonged ReleaseDrug

    Also called - Nucynta, - Palexia

    Participants started with 50 mg, 100 mg or 150 mg tapentadol prolonged release (PR) twice daily. Opioid rotation to tapentadol was scheduled as follows:

    • if less than 100 mg morphine equivalent start with 50 mg tapentadol PR;
    • if on 101 to 160 mg morphine equivalent daily dose start with 100 mg tapentadol PR;
    • if above 161 mg morphine equivalent daily dose start with 150 mg tapentadol PR.

    Tapentadol doses were adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis). After 5 weeks, the doses of tapentadol PR were kept stable (start of Maintenance phase). The tapentadol PR formulation was administered for up to 12 weeks. Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol PR was reached.

Study groups in NCT00986258
Study groupRoleWhat they receive
Tapentadol Prolonged ReleaseExperimentalOther Names: * Nucynta * Palexia
Receives: Drug: Tapentadol Prolonged Release

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants That Responded to Treatment

    Participants were considered responders if they reported the same or less average pain intensity over a 3 day period (NRS-3) after 6 weeks of tapentadol prolonged release treatment compared to their previous analgesic treatment (over a 3 day period on the Numeric Rating Scale) at Week 6 compared with Week-1.

    Measured: 6 weeks

Secondary outcomes (18)

  1. Average Pain Intensity Before the Start of Tapentadol Treatment

    For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".

    Measured: Baseline

  2. Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment.

    For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The value indicates the change from the baseline value on the 0 to 10 scale. A negative value indicates a reduction in pain intensity from the baseline average pain intensity.

    Measured: Baseline; End of Week 6 (6 weeks)

  3. Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment.

    For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The value indicates the change from the baseline value on the 0 to 10 scale. A Negative value indicates a reduction in pain intensity from the baseline average pain intensity.

    Measured: Baseline; End of Week 12 (12 weeks)

  4. Patient Global Impression of Change

    In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.

    Measured: Baseline; End of Week 6 (6 Weeks)

  5. Patient Global Impression of Change

    In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.

    Measured: Baseline; End of Week 12 (12 Weeks)

  6. Change in the Health Survey Scores Form (SF-36)

    The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (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. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline.

    Measured: Baseline; End of Week 6 (6 Weeks)

  7. Change in the Health Survey Scores Form (SF-36)

    The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (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. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline.

    Measured: Baseline; End of Week 12 (12 Weeks)

  8. Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score

    All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant.

    Results are reported as the mean for each neuropathic symptom in the sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).

    Measured: Baseline

  9. Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score

    All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant.

    Results are reported as the mean for each neuropathic symptom in a sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).

    Measured: End of Week 6

  10. Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score

    All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant.

    Results are reported as the mean (average) for each neuropathic symptom in a sub-scale.

    The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).

    Measured: End of Week 12

  11. Mean Equipotency Ratio of Tapentadol Compared to Oxycodone

    Tapentadol was compared to Oxycodone with Oxycodone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Oxycodone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Oxycodone.

    Measured: Baseline; End of Week 6 (6 Weeks)

  12. Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine

    Tapentadol was compared to Buprenorphine with Buprenorphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Buprenorphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Buprenorphine.

    Measured: Baseline; End of Week 6 (6 Weeks)

  13. Mean Equipotency Ratio of Tapentadol Compared to Fentanyl

    Tapentadol was compared to Transdermal Fentanyl with Fentanyl set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Transdermal Fentanyl was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Fentanyl.

    Measured: Baseline; End of Week 6 (6 Weeks)

  14. Mean Equipotency Ratio of Tapentadol Compared to Morphine

    Tapentadol was compared to Morphine with Morphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Morphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Morphine.

    Measured: Baseline; End of Week 6 (6 Weeks)

  15. Mean Equipotency Ratio of Tapentadol Compared to Hydromorphone

    Tapentadol was compared to Hydromorphone with Hydromorphone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Hydromorphone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Hydromorphone.

    Measured: Baseline; End of Week 6 (6 Weeks)

  16. painDETECT Assessment at Baseline

    The painDETECT questionnaire was used to determine the possibility of the presence of a neuropathic pain component. It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".

    Measured: Baseline

  17. painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment

    The baseline painDETECT score was reassessed at the end of Week 6.

    It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".

    Measured: End of Week 6

  18. painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment

    The baseline painDETECT score was reassessed at the end of Week 12.

    It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".

    Measured: End of Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2009 (estimated)
  2. Study start30 Oct 2009
  3. Primary completionDec 2010
  4. Study completionJan 2011

Why it stopped: This clinical trial was terminated early, due to slow recruitment and study drug shortages.

Resources

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 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00986258
Sponsor's protocol ID
835093
Other IDs
2009-010428-25, KF5503/45, 2009
Status last verified
Dec 2018
First submitted
28 Sep 2009
Last updated
9 Jan 2019
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Information available on the Grünenthal Web Site.

Publications

  • Galvez R, Schafer M, Hans G, Falke D, Steigerwald I. Tapentadol prolonged release versus strong opioids for severe, chronic low back pain: results of an open-label, phase 3b study. Adv Ther. 2013 Mar;30(3):229-59. doi: 10.1007/s12325-013-0015-6. Epub 2013 Mar 7.

    PubMed 23475406

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tapentadol Prolonged Release in people with Pain and Chronic Pain, run by Grünenthal GmbH at 27 sites in 8 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 11 inclusion and 21 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: stopped early, as of the sponsor's last update on 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Germany, Spain, Belgium, Netherlands, France and 3 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 18 Mar 2013). 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?

Number of Participants That Responded to Treatment (time frame: 6 weeks). 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 NCT00986258, which also lists 1 linked publication.

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 9 Jan 2019.

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