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

Condition(s) targeted: Chronic Pain Due to Low Back Pain

Intervention: Tapentadol (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Grünenthal GmbH

Official(s) and/or principal investigator(s):
Michael Schäfer, Prof. MD, Principal Investigator, Affiliation: Charité University Berlin, Campus Virchow Klinikum

Overall contact:
Claudia Leinweber, Email: Clinical-Trials@grunenthal.com

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 PR treatment during defined periods of evaluation.

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 design: Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: The primary outcome is the percentage of subjects with the same or less pain (on the NRS-3) at Week 6 compared with Week -1.

Secondary outcome: Changes from baseline of: 11-point NRS-3 pain intensity, Sleep Evaluation Questionnaire (SQ) items, Short Form 36 Health Survey (SF-36) scores, EuroQoL-5 Dimension (EQ- 5D) scores, Hospital Anxiety and Depression Scale (HADS).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subjects 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.

- Subjects 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.

- Subjects must be appropriately communicative to verbalize and to differentiate with

regard to location and intensity of the pain.

- Subjects must be at least 18 years of age.

- Subjects must have a diagnosis of chronic low back pain; chronic pain defined as pain

lasting for at least 3 months

- If the subject has radicular pain, this must have been present for at least 3 months

and stable for the 4 weeks before enrollment.

- Subject's pain must require a strong analgesic (defined as WHO Step III) as judged by

the Investigator.

- Subjects must be taking a WHO Step III analgesic on a daily basis for at least 2

weeks prior to the Screening Visit.

- Subjects must have responded to the WHO Step III analgesic, i. e., subjects must have

a confirmed average pain intensity score (NRS 3) of ≤5 points during the last 3 days prior to the Screening Visit.

- Subjects must report opioid-related side effects as the reason to change their

analgesic.

- Subjects 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). Key exclusion

criteria (trial specific) - at the Screening Visit

- 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.

Claudia Leinweber, Email: Clinical-Trials@grunenthal.com

Site 1, Newcastle, Australia; Completed

Site 2, Perth, Australia; Recruiting

Site 4, Brugges, Belgium; Recruiting

Site 5, Brussels, Belgium; Completed

Site 3, Charleroi, Belgium; Completed

Site 2, Edegem, Belgium; Recruiting

Site 1, Liège, Belgium; Recruiting

Site 1, Brno, Czech Republic; Recruiting

Site 3, Olomouc, Czech Republic; Completed

Site 2, Ostrava, Czech Republic; Completed

Site 2, Montpellier, France; Completed

Site 3, Orléans, France; Completed

Site 4, Thionville, France; Recruiting

Site 1, Toulouse, France; Recruiting

Site 5, Albstadt, Germany; Recruiting

Site 1, Berlin, Germany; Recruiting

Site 2, Berlin, Germany; Not yet recruiting

Site 3, Berlin, Germany; Recruiting

Site 6, Kiel, Germany; Recruiting

Site 4, Leipzig, Germany; Recruiting

Site 8, Leipzig, Germany; Not yet recruiting

Site 7, Stuttgart, Germany; Recruiting

Site 2, Alkmaar, Netherlands; Recruiting

Site 4, Doetinchem, Netherlands; Recruiting

Site 3, Eindhoven, Netherlands; Recruiting

Site 5, Stadskanaal, Netherlands; Completed

Site 1, Tiel, Netherlands; Recruiting

Site 2, Krakow, Poland; Recruiting

Site 1, Poznan, Poland; Recruiting

Site 4, Wroclaw, Poland; Completed

Site 6, Cadiz, Spain; Recruiting

Site 1, Granada, Spain; Recruiting

Site 3, Malaga, Spain; Recruiting

Site 4, Sevilla, Spain; Recruiting

Site 5, Valencia, Spain; Recruiting

Site 1, Basel, Switzerland; Recruiting

Site 2, St. Gallen, Switzerland; Recruiting

Starting date: September 2009
Last updated: June 7, 2010