Tapentadol Prolonged Release (PR) Versus Oxycodone/Naloxone Prolonged Release in Severe Chronic Low Back Pain With a Neuropathic Component.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT01838616
First received: April 19, 2013
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

This is a clinical effectiveness trial designed to compare the effectiveness, safety, and tolerability of treatment with tapentadol prolonged release with that of oxycodone/naloxone prolonged release in non-opioid pre-treated subjects with severe chronic low back pain with a neuropathic pain component.

Both tapentadol and the opioid oxycodone are effective in chronic severe pain and tapentadol and oxycodone /naloxone have shown advantages in gastrointestinal tolerability versus oxycodone. Therefore, it is of high scientific interest to compare the latter 2 analgesics with respect to gastrointestinal tolerability. Tapentadol may have advantages regarding the neuropathic pain-related symptoms of low back pain due to its 2 mechanisms of action.


Condition Intervention Phase
Back Pain
Low Back Pain
Neuropathic Pain
Drug: Tapentadol Prolonged Release
Drug: Oxycodone/Naloxone Prolonged Release
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Effectiveness, Safety, and Tolerability of Tapentadol PR Versus Oxycodone/Naloxone PR in Non-opioid Pre-treated Subjects With Uncontrolled Severe Chronic Low Back Pain With a Neuropathic Pain Component.

Resource links provided by NLM:


Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • Change From Week -1 of the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3) at Week 12 [ Time Frame: Baseline to end of week 12 week ] [ Designated as safety issue: No ]
    For this pain assessment, the participant indicates 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 and varies from -10 to 10.

  • Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) total score over time [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: Yes ]
    The Constipation Assessment (PAC-SYM) is a 12-item self-report questionnaire that assesses the severity of symptoms of constipation. Participants are asked "How severe have each of these symptoms been in the last two weeks?" e.g. "Pain in your stomach". There are 3 subscales: 4 questions on abdominal symptoms, 3 on rectal symptoms and 5 on stool symptoms. Responses are rated on a 5-point Likert scale ranging from 0 (absence of symptom) to 4 (very severe symptoms). If the changes in the overall or subscale scores are positive then there is a worsening in symptoms associated with constipation. The change in the patient's assessment of constipation symptoms (PAC-SYM) total score from the Randomization Visit to the Final Evaluation Visit.


Secondary Outcome Measures:
  • Comparison of typical opioid treatment-emergent side effects [ Time Frame: Baseline; End of Week 3 ] [ Designated as safety issue: Yes ]
    The percentage of participants having the composite treatment emergent adverse events (TEAEs): nausea, vomiting, dizziness and/or somnolence, moderate or severe, during the titration period.

  • Change in the painDETECT assessment [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
    The painDETECT 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".

  • Change in EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
    The participant scores the EuroQol-5. This is a five dimensional health state classification. Each dimension is 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 1.00 indicating "full health" and 0 representing dead. The positive values indicate that during the study the health status improved.

  • Patient Global Impression of Change [ Time Frame: End of Week 12 ] [ 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.

  • Clinician Global Impression of Change [ Time Frame: End of Week 12 ] [ Designated as safety issue: No ]
    In the Clinician Global Impression of Change (CGIC) the clinician 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.

  • Neuropathic Pain Symptom Inventory (NPSI) [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
    In the Neuropathic Pain Symptom Inventory the participant rates their symptoms of neuropathic pain. Ten pain questions are answered on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). Two items related to temporal pain assessed on 5-point scales.

  • Change in the Short Form Health Survey (SF-12) [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
    The Short Form Health Survey (SF-12) includes several brief board 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. 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 Hospital Anxiety Depression Scale; Anxiety Score [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]

    The Hospital Anxiety Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 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 negative value indicates that there has been an improvement.


  • Change in Hospital Anxiety Depression Scale Depression Score [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]

    The Hospital Anxiety Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises of 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 negative value indicates that there has been an improvement.


  • Change score of Sleep evaluation questionnaire [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
    The sleep evaluation questionnaire will be completed by the participant. The questionnaire measures 4 main concepts: latency, time slept, number of awakenings and overall quality of sleep.

  • Change in Work Productivity and Activity Impairment (WPAI) questionnaire [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
    The Work Productivity and Activity Impairment (WPAI) questionnaire is an instrument used to measure impairments in paid and unpaid work and consists of 6 questions.

  • Average pain intensity over three days for pain radiating towards or into the leg [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
  • Worst pain intensity over the past 24 hours [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
  • Recalled average pain intensity [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: No ]
    The recalled average pain intensity score on the NRS-3 will be assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant will be 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.

  • Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) subscores over time [ Time Frame: Baseline; End of Week 12 ] [ Designated as safety issue: Yes ]
    The Constipation Assessment (PAC-SYM) is a 12-item self-report questionnaire that assesses the severity of symptoms of constipation. Participants are asked "How severe have each of these symptoms been in the last two weeks?" e.g. "Pain in your stomach". There are 3 subscales: 4 questions on abdominal symptoms, 3 on rectal symptoms and 5 on stool symptoms. Responses are rated on a 5-point Likert scale ranging from 0 (absence of symptom) to 4 (very severe symptoms). If the changes in the overall or subscale scores are positive then there is a worsening in symptoms associated with constipation. The change in the patient's assessment of constipation symptoms (PAC-SYM) total score from the Randomization Visit to the Final Evaluation Visit.

  • Comparison of typical gastrointestinal opioid treatment-emergent side effects [ Time Frame: Baseline; End of Week 3 ] [ Designated as safety issue: Yes ]
    The percentage of participants having the composite treatment emergent adverse events (TEAEs): nausea and/or vomiting, during the titration period.


Enrollment: 367
Study Start Date: April 2013
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tapentadol Prolonged Release (PR) Drug: Tapentadol Prolonged Release
All participants started with 50 mg tapentadol hydrochloride prolonged release (twice daily). The dose of tapentadol hydrochloride prolonged release will be adjusted in increments of 50 mg to a level that provided adequate analgesia. Titration will be after a minimum of 3 days on a dose. Participants are permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). After titration participants will remain on the stable dose for 9 weeks.
Other Names:
  • Nucynta
  • Palexia
Active Comparator: Oxycodone/Naloxone Prolonged Release Drug: Oxycodone/Naloxone Prolonged Release
All participants start with 10 mg/5 mg oxycodone/naloxone (twice daily). The dose of oxycodone/naloxone may be adjusted in increments of 10mg/ 5 mg oxycodone/naloxone to a level that provide adequate analgesia. Titration will be after a minimum of 3 days on a dose. Participants will be permitted a maximum dose of 50 mg/ 20 mg oxycodone/naloxone twice daily a day (100 mg/40 mg total daily dose). After titration participants will remain on the stable dose for 9 weeks.
Other Name: Targin

  Eligibility

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

Inclusion Criteria:

  • Informed consent signed.
  • Male or female 18 years of age or older.
  • Women of childbearing potential must have a negative pregnancy test at the Enrollment Visit.
  • Women of childbearing potential must practice medically acceptable methods of birth control during the trial.
  • Participant must be appropriately communicative and able to differentiate with regard to location and intensity of the pain, and to complete the questionnaires used in this trial.
  • Participants must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months prior to enrollment.
  • Participant's pain must require a strong analgesic (defined as World Health Organization Step III) as judged by the investigator.
  • Participant's pain must require a strong analgesic (defined as World Health Organization Step III) as judged by the investigator.
  • Participants who do not require a washout of co-analgesics at enrollment must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher.
  • Participants who do not require a washout of co-analgesics at enrollment must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher.
  • The painDETECT diagnostic screening questionnaire must be either "positive" (score of 19 to 38 inclusive) or "unclear" (score of 13 to 18 inclusive). If the participant is being treated with a stable regimen of centrally acting co-analgesics, a "negative" painDETECT score (score 9 points or higher).

Inclusion criteria prior to allocation to treatment:

  • Participants must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher.
  • Participants must score either "positive" (score of 19 to 38 inclusive) or "unclear" (score of 13 to 18 inclusive) on the painDETECT diagnostic screening questionnaire.

Exclusion Criteria:

  • Presence of a clinically significant disease or clinical laboratory values that in the investigator's opinion may affect effectiveness, quality of life, or safety/tolerability assessments.
  • Presence of active systemic or local infections that may, in the opinion of the investigator, affect the effectiveness, quality of life, or safety/tolerability assessments.
  • 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 Enrollment Visit.
  • Known to or suspected of not being able to comply with the protocol and/or appropriate use of the Investigational Medicinal Products.
  • Any painful procedures (e.g., major surgery) scheduled during the trial duration (Enrollment Visit until Final Evaluation Visit) that may, in the opinion of the investigator, affect the effectiveness, quality of life, or safety assessments.
  • Pending litigation or application for insurance/governmental benefits due to chronic pain or disability and/or if the granted benefits might be influenced by a successful participation in the trial.
  • Low back pain caused by cancer and/or metastatic diseases.
  • History of alcohol or drug abuse, or suspicion thereof in the investigator's judgment.
  • Presence of concomitant autoimmune inflammatory conditions.
  • Participants with acute intoxication with alcohol, hypnotics, centrally acting analgesics, or psychotropic active substances.
  • Participants with severe renal impairment, i.e., estimated glomerular filtration rate less than 30 mL/min (according to the National Kidney Foundation 2002).
  • Known history of clinical laboratory values or current clinical laboratory values reflecting moderately or severely impaired hepatic function.
  • 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 (including brain metastases if present at the Enrollment Visit). 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 hours) or residual sequelae.
  • Pregnant or breast-feeding women.
  • Severe respiratory depression with hypoxia and/or hypercapnia, acute or severe bronchial asthma or severe chronic obstructive pulmonary disease.
  • Presence or suspicion of paralytic ileus.
  • Participants with severe cardiac impairment, e.g., New York Heart Association class >3, myocardial infarction less than 6 months prior to the Enrollment Visit, and/or unstable angina pectoris and/or cor pulmonale.
  • Participant with known history of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.
  • History of allergy or hypersensitivity to tapentadol, oxycodone, naloxone, and their formulations.
  • Participants with acute biliary obstruction or acute pancreatitis.
  • Participants with hypothyroidism (including myxedema) or Addison's disease.
  • Participants taking any prohibited concomitant medication.
  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: NCT01838616

  Show 50 Study Locations
Sponsors and Collaborators
Grünenthal GmbH
Investigators
Study Director: Director Clinical Trials Grünenthal GmbH
  More Information

No publications provided

Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT01838616     History of Changes
Other Study ID Numbers: KF5503/60, 2012-002943-11
Study First Received: April 19, 2013
Last Updated: April 4, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Austria: Austrian Medicines and Medical Devices Agency
Spain: Spanish Agency of Medicines

Keywords provided by Grünenthal GmbH:
Severe chronic low back pain
Neuropathic pain
Constipation

Additional relevant MeSH terms:
Back Pain
Low Back Pain
Neuralgia
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Peripheral Nervous System Diseases
Neuromuscular Diseases
Naloxone
Oxycodone
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Narcotics
Central Nervous System Depressants
Analgesics
Analgesics, Opioid

ClinicalTrials.gov processed this record on July 20, 2014