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

NCT00986258 | Terminated Phase 3 Results

• 3 other identifiers: 8350932009-010428-25KF5503/45
• Study Type: interventional
• Target: 136
• Locations: 8 countries
• Sites: 27

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.

Conditions

Pain; Chronic Pain; Low Back Pain; Neuropathic Pain; Nociceptive Pain

Keywords

pain assessment; tapentadol; centrally acting analgesic

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Responded to Treatment

  Participants were considered responders if they reported the same or less average pain intensity over a 3 day period (NRS-3) after 6 weeks of tapentadol prolonged release treatment compared to their previous analgesic treatment (over a 3 day period on the Numeric Rating Scale) at Week 6 compared with Week-1.

  6 weeks

Secondary Outcomes (18)

• Average Pain Intensity Before the Start of Tapentadol Treatment

  Baseline

• Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment.

  Baseline; End of Week 6 (6 weeks)

• Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment.

  Baseline; End of Week 12 (12 weeks)

• Patient Global Impression of Change

  Baseline; End of Week 6 (6 Weeks)

• Patient Global Impression of Change

  Baseline; End of Week 12 (12 Weeks)

Study Arms (1)

Tapentadol Prolonged Release

EXPERIMENTAL

Other Names: * Nucynta * Palexia

Drug: Tapentadol Prolonged Release

Interventions

Tapentadol Prolonged Release DRUG

Participants started with 50 mg, 100 mg or 150 mg tapentadol prolonged release (PR) twice daily. Opioid rotation to tapentadol was scheduled as follows: * if less than 100 mg morphine equivalent start with 50 mg tapentadol PR; * if on 101 to 160 mg morphine equivalent daily dose start with 100 mg tapentadol PR; * if above 161 mg morphine equivalent daily dose start with 150 mg tapentadol PR. Tapentadol doses were adjusted to a level that provided adequate analgesia (upwards or downwards on a weekly basis). After 5 weeks, the doses of tapentadol PR were kept stable (start of Maintenance phase). The tapentadol PR formulation was administered for up to 12 weeks. Tapentadol immediate release 50 mg (no more than twice daily; at least 4 hours apart) was considered as medication for acute pain episodes however, participants were not permitted to dose tapentadol immediate release any more when a daily dose of 500 mg tapentadol PR was reached.

Also known as: - Nucynta, - Palexia

Tapentadol Prolonged Release

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (27)

BE004

Bruges, Belgium

Location

BE003

Charleroi, Belgium

Location

BE002

Edegem, Belgium

Location

BE001

Liège, Belgium

Location

CZ001

Brno, Czechia

Location

FR004

Thionville, France

Location

FR001

Toulouse, France

Location

DE005

Albstadt, Germany

Location

DE001

Berlin, Germany

Location

DE003

Berlin, Germany

Location

DE006

Kiel, Germany

Location

DE004

Leipzig, Germany

Location

DE008

Leipzig, Germany

Location

DE007

Stuttgart, Germany

Location

NL002

Alkmaar, Netherlands

Location

NL004

Doetinchem, Netherlands

Location

NL003

Eindhoven, Netherlands

Location

NL001

Tiel, Netherlands

Location

PL002

Krakow, Poland

Location

PL001

Poznan, Poland

Location

ES006

Cadiz, Spain

Location

ES001

Granada, Spain

Location

ES003

Málaga, Spain

Location

ES004

Seville, Spain

Location

ES005

Valencia, Spain

Location

CH001

Basel, Switzerland

Location

CH002

Sankt Gallen, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 23475406 RESULT

MeSH Terms

Conditions

Pain; Chronic Pain; Low Back Pain; Neuralgia; Nociceptive Pain

Interventions

Tapentadol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Back Pain; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

The results of this trial have to be interpreted under the consideration that it was an open-label trial which was prematurely terminated.

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Grünenthal GmbH

clinical-trials@grunenthal.com

+49 241 569 3223

Study Officials

• Michael Schäfer, Prof. MD

  Charité University Berlin, Campus Virchow Klinikum

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2009
• First Posted: September 29, 2009
• Study Start: October 30, 2009
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2011
• Last Updated: January 9, 2019
• Results First Posted: March 18, 2013

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

FR (2); CZ (1); CH (2); BE (4); DE (7); NL (4); PL (2); ES (5)