Clinical trial NCT01838616: Tapentadol Prolonged Release (PR) Versus Oxycodone/Naloxone Prolonged Release in Severe Chronic Low Back Pain With a Neuropathic Component.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Back Pain
Low Back Pain
Neuropathic Pain
Keywords: Severe chronic low back pain
Neuropathic pain
Constipation
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2013-04-24
Enrollment: 367
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was 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 was 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.


Eligibility 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.
* Participants who require a washout of co-analgesics at enrolment must have an average pain score (NRS-3) of 5 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 suggesting transient changes in consciousness.
* 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.

Primary outcomes:
measure: Change in the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3)
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) Total Score
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
Secondary outcomes:
measure: Recalled Average Pain Intensity
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change in Recalled Average Pain Intensity at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change of Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Worst Pain Intensity Over the Past 24 Hours
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change in Worst Pain Intensity Over the Past 24 Hours at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: painDETECT Final Assessment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change in painDETECT Final Assessment at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Short Form Health Survey (SF-12)
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Changes in the Short Form Health Survey (SF-12) at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: EuroQol-5 (EQ-5D) Health Status Index Outcome
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change in EuroQol-5 (EQ-5D) Health Status Index Outcome at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Hospital Anxiety and Depression Scale: Anxiety
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change in Hospital Anxiety and Depression Scale at the End of Treatment: Anxiety
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Hospital Anxiety and Depression Scale: Depression
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Change in Hospital Anxiety and Depression Scale at the End of Treatment: Depression
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Patient Global Impression of Change at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Clinician Global Impression of Change at the End of Treatment
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Sleep Evaluation at the End of Treatment: Change in the Overall Quality of Sleep
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Sleep Evaluation: Number of Awakenings
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Sleep Evaluation at the End of Treatment: Change in the Number of Awakenings
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Sleep Evaluation: Number of Hours Slept
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Sleep Evaluation at the End of Treatment: Change in the Number of Hours Slept
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Sleep Evaluation: Latency (Time Taken to Fall Asleep)
timeFrame: Baseline (Randomization Visit); End of Continuation Period (Week 12)
measure: Sleep Evaluation at the End of Treatment: Change in Latency (Change in the Time Taken to Fall Asleep)
timeFrame: Baseline (Randomization Visit); End of Continuation Visit (Week 12)
measure: Comparison of the Number of Participants Affected by Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids
timeFrame: Baseline (Randomization Visit) to End of Titration Period (End of Week 3)
measure: Composite Event Based Comparison of Gastrointestinal Treatment Emergent Adverse Events (TEAEs) Typical for Opioids
timeFrame: Baseline (Randomization Visit); End of Week 3 (End of Titration Period)
Other outcomes:
Locations:
city: Senftenberg
country: Austria
facility: AT001
city: Vienna
country: Austria
facility: AT002
city: Bad Saarow
country: Germany
facility: DE005
city: Berlin
country: Germany
facility: DE007
city: Berlin
country: Germany
facility: DE021
city: Berlin
country: Germany
facility: DE009
city: Berlin
country: Germany
facility: DE030
city: Bochum
country: Germany
facility: DE020
city: Böhlen
country: Germany
facility: DE023
city: Cottbus
country: Germany
facility: DE028
city: Dresden
country: Germany
facility: DE012
city: Essen
country: Germany
facility: DE032
city: Frankfurt
country: Germany
facility: DE017
city: Frankfurt
country: Germany
facility: DE003
city: Görlitz
country: Germany
facility: DE011
city: Hamburg
country: Germany
facility: DE031
city: Hannover
country: Germany
facility: DE013
city: Kiel
country: Germany
facility: DE001
city: Kiel
country: Germany
facility: DE027
city: Kiel
country: Germany
facility: DE014
city: Köln
country: Germany
facility: DE029
city: Köln
country: Germany
facility: DE008
city: Leipzig
country: Germany
facility: DE004
city: Leipzig
country: Germany
facility: DE034
city: Leipzig
country: Germany
facility: DE018
city: Magdeburg
country: Germany
facility: DE015
city: Mainz
country: Germany
facility: DE006
city: Mittweida
country: Germany
facility: DE002
city: Rudolstadt
country: Germany
facility: DE010
city: Schwerin
country: Germany
facility: DE025
city: Stadtroda
country: Germany
facility: DE019
city: Weinheim
country: Germany
facility: DE016
city: Westerstede
country: Germany
facility: DE024
city: Wiesbaden
country: Germany
facility: DE026
city: Wiesbaden
country: Germany
facility: DE022
city: Catania
country: Italy
facility: IT003
city: Genova
country: Italy
facility: IT001
city: Parma
country: Italy
facility: IT002
city: Pavia
country: Italy
facility: IT004
city: Varese
country: Italy
facility: IT005
city: A Coruna
country: Spain
facility: ES006
city: Barcelona
country: Spain
facility: ES007
city: Barcelona
country: Spain
facility: ES001
city: Centelles
country: Spain
facility: ES003
city: Guadix
country: Spain
facility: ES008
city: Madrid
country: Spain
facility: ES002
city: Madrid
country: Spain
facility: ES010
city: Madrid
country: Spain
facility: ES009
city: Oviedo
country: Spain
facility: ES004
city: Santiago de Compostela
country: Spain
facility: ES005
Study officials:
affiliation: Grünenthal GmbH
name: Director Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Baron R, Likar R, Martin-Mola E, Blanco FJ, Kennes L, Muller M, Falke D, Steigerwald I. Effectiveness of Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR for the Management of Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-Label, Phase 3b/4 Study. Pain Pract. 2016 Jun;16(5):580-99. doi: 10.1111/papr.12308. Epub 2015 Jun 12.