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

This study has been terminated.
(This clinical trial was terminated early, due to slow recruitment and study drug shortages.)
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT00986258
First received: September 28, 2009
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Pain
Chronic Pain
Low Back Pain
Neuropathic Pain
Nociceptive Pain
Drug: Tapentadol Prolonged Release
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • Number of Participants That Responded to Treatment [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    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 as with their previous analgesic treatment (over a 3 day period on the Numeric Rating Scale) at Week 6 compared with Week-1.


Secondary Outcome Measures:
  • Average Pain Intensity Before the Start of Tapentadol Treatment [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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".

  • Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment. [ Time Frame: Baseline; End of Week 6 (6 weeks) ] [ Designated as safety issue: No ]
    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.

  • Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment. [ Time Frame: Baseline; End of Week 12 (12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Patient Global Impression of Change [ Time Frame: Baseline; End of Week 6 (6 Weeks) ] [ Designated as safety issue: No ]
    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.

  • Patient Global Impression of Change [ Time Frame: Baseline; End of Week 12 (12 Weeks) ] [ Designated as safety issue: No ]
    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.

  • Change in the Health Survey Scores Form (SF-36) [ Time Frame: Baseline; End of Week 6 (6 Weeks) ] [ Designated as safety issue: No ]
    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.

  • Change in the Health Survey Scores Form (SF-36) [ Time Frame: Baseline; End of Week 12 (12 Weeks) ] [ Designated as safety issue: No ]
    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.

  • Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    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).


  • Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score [ Time Frame: End of Week 6 ] [ Designated as safety issue: No ]

    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).


  • Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score [ Time Frame: End of Week 12 ] [ Designated as safety issue: No ]

    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).


  • Mean Equipotency Ratio of Tapentadol Compared to Oxycodone [ Time Frame: Baseline; End of Week 6 (6 Weeks) ] [ Designated as safety issue: No ]
    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.

  • Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine [ Time Frame: Baseline; End of Week 6 (6 Weeks) ] [ Designated as safety issue: No ]
    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.

  • Mean Equipotency Ratio of Tapentadol Compared to Fentanyl [ Time Frame: Baseline; End of Week 6 (6 Weeks) ] [ Designated as safety issue: No ]
    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.

  • Mean Equipotency Ratio of Tapentadol Compared to Morphine [ Time Frame: Baseline; End of Week 6 (6 Weeks) ] [ Designated as safety issue: No ]
    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.

  • Mean Equipotency Ratio of Tapentadol Compared to Hydromorphone [ Time Frame: Baseline; End of Week 6 (6 Weeks) ] [ Designated as safety issue: No ]
    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.

  • painDETECT Assessment at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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".

  • painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment [ Time Frame: End of Week 6 ] [ Designated as safety issue: No ]

    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".


  • painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment [ Time Frame: End of Week 12 ] [ Designated as safety issue: No ]

    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".



Enrollment: 136
Study Start Date: October 2009
Study Completion Date: January 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tapentadol Prolonged Release

Other Names:

  • Nucynta
  • Palexia
Drug: Tapentadol Prolonged Release

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

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

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 prolonged release was kept stable (start of Maintenance phase). 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 once 500 mg tapentadol prolonged release dose was reached.

Other Names:
  • - Nucynta
  • - Palexia

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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).

Exclusion Criteria:

  • 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00986258

Locations
Belgium
BE004
Brugges, Belgium
BE003
Charleroi, Belgium
BE002
Edegem, Belgium
BE001
Liège, Belgium
Czech Republic
CZ001
Brno, Czech Republic
France
FR004
Thionville, France
FR001
Toulouse, France
Germany
DE005
Albstadt, Germany
DE001
Berlin, Germany
DE003
Berlin, Germany
DE006
Kiel, Germany
DE004
Leipzig, Germany
DE008
Leipzig, Germany
DE007
Stuttgart, Germany
Netherlands
NL002
Alkmaar, Netherlands
NL004
Doetinchem, Netherlands
NL003
Eindhoven, Netherlands
NL001
Tiel, Netherlands
Poland
PL002
Krakow, Poland
PL001
Poznan, Poland
Spain
ES006
Cadiz, Spain
ES001
Granada, Spain
ES003
Malaga, Spain
ES004
Sevilla, Spain
ES005
Valencia, Spain
Switzerland
CH001
Basel, Switzerland
CH002
St. Gallen, Switzerland
Sponsors and Collaborators
Grünenthal GmbH
Investigators
Principal Investigator: Michael Schäfer, Prof. MD Charité University Berlin, Campus Virchow Klinikum
  More Information

No publications provided by Grünenthal GmbH

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT00986258     History of Changes
Other Study ID Numbers: 835093, 2009-010428-25
Study First Received: September 28, 2009
Results First Received: May 31, 2012
Last Updated: May 9, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Spanish Agency of Medicines
Poland: The Central Register of Clinical Trials
Czech Republic: State Institute for Drug Control
Switzerland: Swissmedic
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Grünenthal GmbH:
pain assessment
tapentadol
centrally acting analgesic

Additional relevant MeSH terms:
Back Pain
Low Back Pain
Chronic Pain
Neuralgia
Nociceptive Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Peripheral Nervous System Diseases
Neuromuscular Diseases
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014