Evaluation of the effectiveness, safety, and tolerability of tapentadol PR versus a combination of tapentadol PR and pregabalin in subjects with severe chronic low back pain with a neuropathic pain component

• Register: EUCTR
• Last refreshed on: 8 April 2013
• Main ID: EUCTR2010-019998-14-DE
• Date of registration: 06/12/2010
• Prospective Registration: Yes
• Primary sponsor: Grünenthal GmbH
• Public title: Evaluation of the effectiveness, safety, and tolerability of tapentadol PR versus a combination of tapentadol PR and pregabalin in subjects with severe chronic low back pain with a neuropathic pain component
• Scientific title: Evaluation of the effectiveness, safety, and tolerability of tapentadol PR versus a combination of tapentadol PR and pregabalin in subjects with severe chronic low back pain with a neuropathic pain component
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019998-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Denmark, Germany, Netherlands, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Key inclusion criteria (general) at the Enrollment Visit
1. 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.
2. Male or female subject =18 years of age.
3. Women of childbearing potential must have a negative pregnancy test at the Enrollment Visit.
4. 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, contraceptive patch, male partner sterilization) before entry and throughout the trial.
5. Subjects 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.

Key inclusion criteria (trial specific) at the Enrollment Visit
6. Subjects must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months.
7. Subject’s pain must require a strong analgesic (defined as WHO step III) as judged by the Investigator.
8. The painDETECT diagnostic screening questionnaire score must be:
• “positive” or
• “unclear”.
or
If the subject is being treated with a stable regimen of centrally acting analgesics (opioids) and/or co-analgesics, even a “negative” painDETECT score (but of at least 9) at the Enrollment Visit will be acceptable.
9. If under regular daily pretreatment with a WHO step II/step III opioid analgesic and/or a centrally acting co-analgesic:
• Subjects must be taking a WHO step II or step III analgesic or co-analgesic on a daily basis for at least 2 weeks prior to the Enrollment Visit.
• Subjects pretreated with a WHO step II opioid analgesic and/or a centrally acting co-analgesic must have reported an average pain intensity score of at least 5 points (NRS-3 =5) during the last 3 days prior to the Enrollment Visit.
or
If under regular, daily pretreatment with a WHO step I analgesic monotherapy or if no regular analgesic pretreatment is reported:
• Subjects must have an average pain intensity score of at least 6 points (NRS-3 =6) in the last 3 days prior to the Enrollment Visit.

Key inclusion criteria at the Baseline Visit
10. To be eligible to enter the trial, the subjects have to fulfill the inclusion criteria and not meet any of the exclusion criteria at the Enrollment Visit. The following criteria have to be confirmed at the Baseline Visit after 3 days to 2 weeks of washout of opioids and centrally acting co-analgesics and after the results of the laboratory analyses have been received).
• Subjects must have an average pain intensity score (NRS-3) of at least 6 points (NRS-3 =6).
• Subjects must score “positive” or “unclear” on the painDETECT diagnostic screening questionnaire at the Baseline Visit.
• Subjects must have an increase of at least 1 point on the NRS-3 compared with the Enrollment Visit if under regular previous analgesic therapy with a WHO step II or step III opioid (post washout).
Subjects will only receive IMP if documentation is available showing that
they comply with these inclusion criteria.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Key exclusion criteria (general) at the Enrollment Visit
Any of the following will exclude subjects from the trial:
1. Presence of a clinically significant disease or laboratory findings that in the Investigator’s opinion may affect efficacy or safety assessments.
2. 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.
3. History of alcohol or drug abuse, or suspicion thereof in the Investigator’s judgment.
4. Presence of concomitant autoimmune inflammatory conditions.
5. Moderate renal impairment (creatinine clearance <60 mL/min).
6. Known history of or laboratory values reflecting current moderately or severely impaired hepatic function.
7. History of seizure disorder or epilepsy.
8. Any of the following within 1 year of enrollment: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm. Severe traumatic brain injury within 15 years of enrollment (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.
9. Pregnant or breast-feeding women.
10. History of allergy or hypersensitivity to tapentadol, pregabalin, paracetamol or their excipients.
11. Contraindications and warnings related to tapentadol, pregabalin, or paracetamol not covered by other exclusion criteria including:
• Acute or severe bronchial asthma.
• Severe respiratory depression with hypoxia and/or hypercapnia.
• Cor pulmonale.
• Severe chronic obstructive pulmonary disease.
• Presence or suspicion of non-opioid induced paralytic ileus.
12. Subjects with severe cardiac impairment, e.g., New York Heart Association class >3, myocardial infarction less than 6 months prior to enrollment, and/or unstable angina pectoris.
13. 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 or employees of the Investigator.
14. Participation in another trial concurrently, or within 4 weeks prior to the Enrollment Visit.
15. Known to or suspected of not being able to comply with the protocol and the use of the IMPs.
16. Use of monoamine oxidase inhibitors within 14 days before the Enrollment Visit.
17. Non-stable dosing of selective serotonin reuptake inhibitors within 30 days before the Enrollment Visit (the doses must remain stable during the trial).

Key exclusion criteria (trial specific) at the Enrollment Visit
18. Presence of concomitant painful conditions other than low back pain that could confound the subject’s trial assessments or self-evaluation of the index pain, e.g., syndromes with widespread pain such as fibromyalgia.
19. Low back pain caused by cancer and/or metastatic diseases.
20. Any painful procedures planned during the trial period (e.g., major surgery) that may, in the opinion of the Investigator, affect the effectiveness or safety assessments of the IMP.
21. Pending litigation or application for insurance/governmental benefits due to chronic pain or disability and, if granted, benefits might be influenced by a successful participation in the trial.
22. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption, lactose intolerance.

Subjects will only receive IMP if documentation is

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

severe chronic low back pain with a neuropathic pain component
MedDRA version: 12.1 Level: LLT Classification code 10024891 Term: Low back pain
MedDRA version: 12.1 Level: LLT Classification code 10054095 Term: Neuropathic pain

Intervention(s)

Product Name: Tapentadol 50 mg PR2 tablet
Product Code: CG5503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Tapentadol 150 mg PR2 tablet
Product Code: CG5503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Name: Tapentadol 200 mg PR2 tablet
Product Code: CG5503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Product Name: Tapentadol 250 mg PR2 tablet
Product Code: CG5503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: PALEXIA® retard 50 mg
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: PALEXIA® retard 100 mg
Pharmaceutical Fo

Primary Outcome(s)

Secondary Objective: • To evaluate the impact of tapentadol PR and a combination of tapentadol PR and
pregabalin on function and quality of life parameters (subject-reported outcomes) in
subjects with severe low back pain with a neuropathic pain component.
• To evaluate a subset of subjects satisfied with moderate doses of tapentadol PR (300 mg per day)
• To evaluate responder profiles based on painDETECT sub-profiles.

Primary end point(s): Comparison of tapentadol PR 300 mg plus 200 mg per day and the combination of tapentadol PR 300 mg per day and pregabalin 300 mg per day regarding the change in NRS-3 pain intensity scores from the Randomization Visit to the Final Evaluation Visit.

Main Objective: The primary objective is to evaluate the effectiveness, safety, and tolerability of increasing doses of tapentadol PR (300 mg per day after run-in, up-titration to 500 mg per day) versus a combination of tapentadol PR (300 mg per day after run-in) and pregabalin (titrated to 300 mg per day) in subjects requiring additional analgesia after titration to tapentadol PR 300 mg per day.

Secondary ID(s)

2010-019998-14-NL

KF5503/58