Clinical trial NCT00983385: Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Chronic Low Back Pain Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics
Official title: An Evaluation of the Effectiveness and Tolerability of Tapentadol Hydrochloride Prolonged Release, and Tapentadol Hydrochloride Immediate Release on Demand, in Subjects With Uncontrolled Severe Chronic Nociceptive, Mixed or Neuropathic Low Back Pain Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Pain
Low Back Pain
Keywords: low back pain
pain
assessment
tapentadol
centrally acting analgesic
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2009-09-24
Enrollment: 208
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 either WHO Step I or Step II analgesics or no regular analgesics. 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 (either WHO Step I or Step II analgesics or no regular analgesics) with that of tapentadol hydrochloride prolonged release (PR) treatment during defined periods of evaluation.


Eligibility criteria: Inclusion Criteria:

* Participants must have signed an Informed Consent Form.
* Participants were men or non-pregnant, non-lactating women. Female participants must be postmenopausal, surgically sterile, or practicing an effective method of birth control. 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.
* Participants's pain must require a strong analgesic (defined as WHO Step III) as judged by the Investigator.
* 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).
* If under regular, daily pretreatment:

  * Participants must be taking a WHO Step I or Step II analgesic medication on a daily basis for at least 2 weeks prior to the Screening Visit.
  * The Investigator considers dose increase of WHO Step I analgesics (as mono- or combination therapy) and/or continuation with or dose increase of WHO Step II analgesics inadequate for the individual participant, whatever applicable.
  * Participants must have an average pain intensity score (NRS 3) greater than 5 points during the last 3 days prior to the Screening Visit. or
* If no regular analgesic pretreatment is reported:

  * Participants must have an average pain intensity score (NRS-3) greater than 6 points in the last 3 days prior to the Screening Visit and related to low back pain.

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:
* Participants with acute or severe bronchial asthma or hypercapnia.
* Participants 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 conditions other than low back pain that could confound the assessment or self evaluation of pain, e.g., anatomical deformities, significant skin conditions such as abscess or syndromes with widespread pain such as fibromyalgia.
* Any concomitant painful condition that could interfere with the subject's trial assessments or with their ability to differentiate low back pain from other painful conditions.
* 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.
* Intake of Step III analgesics within the 30 days prior to the Screening Visit.

Primary outcomes:
measure: The Primary Endpoint is Defined as the Change of the Average Pain Intensity Score on an 11-point NRS-3 at Week 6 From Week -1 (Baseline).
timeFrame: Baseline; End of Week 6 (6 Weeks)
Secondary outcomes:
measure: Patient Global Impression of Change at End of Titration and Optimal Dose Period
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: Patient Global Impression of Change at End of the Maintenance Period
timeFrame: Baseline; End of Week 12 (12 weeks)
measure: Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period
timeFrame: Baseline; End of Week 6 (6 weeks)
measure: Change in the Health Survey Scores Form (SF-36) at End of Maintenance Period
timeFrame: Baseline; End of Week 12 (12 weeks)
measure: painDETECT Assessment at Baseline
timeFrame: Baseline
measure: painDETECT Assessment for Participants at End of Titration and Optimal Dose Period
timeFrame: End of Week 6
measure: painDETECT Assessment for Participants at End of the Maintenance Period
timeFrame: End of Week 12
measure: Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at Baseline
timeFrame: Baseline Visit
measure: Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score at End of Titration and Optimal Dose Period
timeFrame: End of Week 6
measure: Neuropathic Pain Symptom Inventory (NPSI) Subscores and Overall Score Assessment at End of the Maintenance Period
timeFrame: End of Week 12
measure: Change in Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of Titration and Optimal Dose Period
timeFrame: Baseline; End of Week 6 (6 Weeks)
measure: Change in Neuropathic Pain Symptom Inventory (NPSI) Final Score Assessment at End of the Maintenance Period
timeFrame: Baseline; End of Week 12 (12 Weeks)
measure: EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Titration and Optimal Dose Period.
timeFrame: Baseline; End of Week 6 (6 weeks)
measure: Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)at End of Titration and Optimal Dose Period.
timeFrame: Baseline; End of Week 6 (6 weeks)
measure: EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time at End of Maintenance Period
timeFrame: Baseline; End of Week 12 (12 weeks)
measure: Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) at End of Maintenance Period
timeFrame: Baseline; End of Week 12 (12 weeks)
measure: Clinical Global Impression of Change (All Participants) at End of Titration and Optimal Dose Period
timeFrame: Baseline; End of Week 6 (6 weeks)
measure: Clinical Global Impression of Change (All Participants) at End of Maintenance Period
timeFrame: Baseline; End of Week 12 (12 weeks)
measure: Hospital Anxiety Depression Scale (HADS): Anxiety Score at Baseline
timeFrame: Baseline
measure: Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Titration and Optimal Dose Period
timeFrame: Baseline; End of Week 6 (6 weeks)
measure: Hospital Anxiety Depression Scale: Change in Anxiety Score at End of Maintenance Period
timeFrame: Baseline; End of Week 12 (12 Weeks)
measure: Hospital Anxiety Depression Scale: Depression Score at Baseline
timeFrame: Baseline
measure: Hospital Anxiety Depression Scale: Change in Depression Score at End of Titration and Optimal Dose Period.
timeFrame: Baseline; End of Week 6 (6 weeks)
measure: Hospital Anxiety Depression Scale: Change in Depression Score at End of Maintenance Period
timeFrame: Baseline; End of Week 12 (12 Weeks)
measure: Final Stable Tapentadol PR Dose in Opioid Naive Participants at End of Titration and Optimal Dose Period.
timeFrame: Week 6
measure: Participant's Satisfaction With Previous Analgesic Treatment at Baseline
timeFrame: Baseline
measure: Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at the End of Titration and Optimal Dose Period.
timeFrame: End of Week 6
measure: Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, in the Maintenance Period.
timeFrame: End of Week 8
measure: Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol, at End of the Maintenance Period.
timeFrame: End of Week 12
measure: Baseline NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment, at Baseline.
timeFrame: Baseline
measure: NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Titration and Optimal Dose Period.
timeFrame: End of Week 6
measure: NRS-3 Pain Intensity in Participants With No Prior Opioid Treatment at the End of the Maintenance Period.
timeFrame: End of Week 12
measure: Baseline NRS-3 Pain Intensity in Participants With Prior Opioid Treatment, at Baseline.
timeFrame: Baseline
measure: NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Titration and Optimal Dose Period.
timeFrame: End of Week 6
measure: NRS-3 Pain Intensity Assessment in Participants With Prior Opioid Treatment at the End of the Maintenance Period.
timeFrame: End of Week 12
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Site 5
city: Vienna
country: Austria
facility: Site 1
city: Vienna
country: Austria
facility: Site 2
city: Vienna
country: Austria
facility: Site 3
city: Vienna
country: Austria
facility: Site 4
city: Karlovac
country: Croatia
facility: Site 3
city: Opatija
country: Croatia
facility: Site 2
city: Sisak
country: Croatia
facility: Site 1
city: Chateaugiron
country: France
facility: Site 2
city: La Seyne sur Mer
country: France
facility: Site 4
city: Murs Erigné
country: France
facility: Site 3
city: Paris
country: France
facility: Site 1
city: Berlin
country: Germany
facility: Site 3
city: Böblingen
country: Germany
facility: Site 7
city: Celle
country: Germany
facility: Site 4
city: Dresden
country: Germany
facility: Site 1
city: Hannover
country: Germany
facility: Site 6
city: Leipzig
country: Germany
facility: Site 8
city: Lünen
country: Germany
facility: Site 5
city: Wiesbaden
country: Germany
facility: Site 2
city: Bologna
country: Italy
facility: Site 6
city: Catania
country: Italy
facility: Site 5
city: Genova
country: Italy
facility: Site 2
city: Parma
country: Italy
facility: Site 4
city: Pavia
country: Italy
facility: Site 3
city: Rome
country: Italy
facility: Site 1
city: Lublin
country: Poland
facility: Site 1
city: Tychy
country: Poland
facility: Site 4
city: Wroclaw
country: Poland
facility: Site 3
city: Alicante
country: Spain
facility: Site 5
city: Badalona
country: Spain
facility: Site 1
city: Guadalajara
country: Spain
facility: Site 7
city: Madrid
country: Spain
facility: Site 6
city: Oviedo
country: Spain
facility: Site 4
city: Pamplona
country: Spain
facility: Site 8
city: Valencia
country: Spain
facility: Site 3
city: Morges
country: Switzerland
facility: Site 1
city: Valens
country: Switzerland
facility: Site 2
city: Belfast
country: United Kingdom
facility: Site 7
city: Bristol
country: United Kingdom
facility: Site 2
city: Chelmsford
country: United Kingdom
facility: Site 8
city: Edinburgh
country: United Kingdom
facility: Site 6
city: Glasgow
country: United Kingdom
facility: Site 1
city: London
country: United Kingdom
facility: Site 4
city: London
country: United Kingdom
facility: Site 5
city: Plymouth
country: United Kingdom
facility: Site 3
Study officials:
affiliation: Medical University / AKH Vienna
name: Hans Kress, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Steigerwald I, Muller M, Davies A, Samper D, Sabatowski R, Baron R, Rozenberg S, Szczepanska-Szerej A, Gatti A, Kress HG. Effectiveness and safety of tapentadol prolonged release for severe, chronic low back pain with or without a neuropathic pain component: results of an open-label, phase 3b study. Curr Med Res Opin. 2012 Jun;28(6):911-36. doi: 10.1185/03007995.2012.679254. Epub 2012 May 9.