Clinical trial NCT00986258: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pain
Chronic Pain
Low Back Pain
Neuropathic Pain
Nociceptive Pain
Keywords: pain assessment
tapentadol
centrally acting analgesic
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2009-09-29
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants That Responded to Treatment
timeFrame: 6 weeks
Secondary outcomes:
measure: Average Pain Intensity Before the Start of Tapentadol Treatment
timeFrame: Baseline
measure: Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment.
timeFrame: Baseline; End of Week 6 (6 weeks)
measure: Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment.
timeFrame: Baseline; End of Week 12 (12 weeks)
measure: Patient Global Impression of Change
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: Patient Global Impression of Change
timeFrame: Baseline; End of Week 12 (12 Weeks)
measure: Change in the Health Survey Scores Form (SF-36)
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: Change in the Health Survey Scores Form (SF-36)
timeFrame: Baseline; End of Week 12 (12 Weeks)
measure: Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
timeFrame: Baseline
measure: Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
timeFrame: End of Week 6
measure: Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score
timeFrame: End of Week 12
measure: Mean Equipotency Ratio of Tapentadol Compared to Oxycodone
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: Mean Equipotency Ratio of Tapentadol Compared to Fentanyl
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: Mean Equipotency Ratio of Tapentadol Compared to Morphine
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: Mean Equipotency Ratio of Tapentadol Compared to Hydromorphone
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: painDETECT Assessment at Baseline
timeFrame: Baseline
measure: painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment
timeFrame: End of Week 6
measure: painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment
timeFrame: End of Week 12
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: BE004
city: Charleroi
country: Belgium
facility: BE003
city: Edegem
country: Belgium
facility: BE002
city: Liège
country: Belgium
facility: BE001
city: Brno
country: Czechia
facility: CZ001
city: Thionville
country: France
facility: FR004
city: Toulouse
country: France
facility: FR001
city: Albstadt
country: Germany
facility: DE005
city: Berlin
country: Germany
facility: DE001
city: Berlin
country: Germany
facility: DE003
city: Kiel
country: Germany
facility: DE006
city: Leipzig
country: Germany
facility: DE004
city: Leipzig
country: Germany
facility: DE008
city: Stuttgart
country: Germany
facility: DE007
city: Alkmaar
country: Netherlands
facility: NL002
city: Doetinchem
country: Netherlands
facility: NL004
city: Eindhoven
country: Netherlands
facility: NL003
city: Tiel
country: Netherlands
facility: NL001
city: Krakow
country: Poland
facility: PL002
city: Poznan
country: Poland
facility: PL001
city: Cadiz
country: Spain
facility: ES006
city: Granada
country: Spain
facility: ES001
city: Malaga
country: Spain
facility: ES003
city: Sevilla
country: Spain
facility: ES004
city: Valencia
country: Spain
facility: ES005
city: Basel
country: Switzerland
facility: CH001
city: St. Gallen
country: Switzerland
facility: CH002
Study officials:
affiliation: Charité University Berlin, Campus Virchow Klinikum
name: Michael Schäfer, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.