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

Pain Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00986258
• Other study ID #: 835093
• Secondary ID: 2009-010428-25KF
• Status: Terminated
• Phase: Phase 3
• Start date: October 30, 2009
• Est. completion date: January 2011

Study information

• Verified date: December 2018
• Source: Grünenthal GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 136
• Est. completion date: January 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Back Pain
• Chronic Pain
• Low Back Pain
• Neuralgia
• Neuropathic Pain
• Nociceptive Pain
• Pain

Intervention

Drug:
• Tapentadol Prolonged Release
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.

Locations

Country	Name	City	State
Belgium	BE004	Brugge
Belgium	BE003	Charleroi
Belgium	BE002	Edegem
Belgium	BE001	Liège
Czechia	CZ001	Brno
France	FR004	Thionville
France	FR001	Toulouse
Germany	DE005	Albstadt
Germany	DE001	Berlin
Germany	DE003	Berlin
Germany	DE006	Kiel
Germany	DE004	Leipzig
Germany	DE008	Leipzig
Germany	DE007	Stuttgart
Netherlands	NL002	Alkmaar
Netherlands	NL004	Doetinchem
Netherlands	NL003	Eindhoven
Netherlands	NL001	Tiel
Poland	PL002	Krakow
Poland	PL001	Poznan
Spain	ES006	Cadiz
Spain	ES001	Granada
Spain	ES003	Malaga
Spain	ES004	Sevilla
Spain	ES005	Valencia
Switzerland	CH001	Basel
Switzerland	CH002	St. Gallen

Sponsors (1)

Lead Sponsor	Collaborator
Grünenthal GmbH

Countries where clinical trial is conducted

Belgium,  Czechia,  France,  Germany,  Netherlands,  Poland,  Spain,  Switzerland, 

References & Publications (1)

Gálvez R, Schäfer 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Average Pain Intensity Before the Start of Tapentadol Treatment	For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".	Baseline
Secondary	Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment.	For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The value indicates the change from the baseline value on the 0 to 10 scale. A negative value indicates a reduction in pain intensity from the baseline average pain intensity.	Baseline; End of Week 6 (6 weeks)
Secondary	Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment.	For this pain assessment, the participant was to indicate the level of average pain experienced over the previous 3 days on an 11-point Numerical Rating Scale(NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The value indicates the change from the baseline value on the 0 to 10 scale. A Negative value indicates a reduction in pain intensity from the baseline average pain intensity.	Baseline; End of Week 12 (12 weeks)
Secondary	Patient Global Impression of Change	In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.	Baseline; End of Week 6 (6 Weeks)
Secondary	Patient Global Impression of Change	In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.	Baseline; End of Week 12 (12 Weeks)
Secondary	Change in the Health Survey Scores Form (SF-36)	The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline.	Baseline; End of Week 6 (6 Weeks)
Secondary	Change in the Health Survey Scores Form (SF-36)	The Scores Form 36 (SF-36) includes several brief questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. A positive mean value indicates an improvement from baseline.	Baseline; End of Week 12 (12 Weeks)
Secondary	Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score	All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant.; Results are reported as the mean for each neuropathic symptom in the sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).	Baseline
Secondary	Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score	All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant.; Results are reported as the mean for each neuropathic symptom in a sub-scale. The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).	End of Week 6
Secondary	Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score	All participants were requested to complete the NPSI (Neuropathic Pain Symptom Inventory) questionnaire at this visit. Each participant rated their own neuropathic pain symptoms by answering ten questions relating to neuropathic symptoms on an 11-point scale 0 (not present) to 10 (worst imaginable) for each question. The higher the score for a question (sub-scale) the more bothersome the symptom is for the participant.; Results are reported as the mean (average) for each neuropathic symptom in a sub-scale.; The mean score is reported on a scale of 0 (not present in the group) to 1 (symptom has the maximum imaginable intensity for the whole group).	End of Week 12
Secondary	Mean Equipotency Ratio of Tapentadol Compared to Oxycodone	Tapentadol was compared to Oxycodone with Oxycodone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Oxycodone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Oxycodone.	Baseline; End of Week 6 (6 Weeks)
Secondary	Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine	Tapentadol was compared to Buprenorphine with Buprenorphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Buprenorphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Buprenorphine.	Baseline; End of Week 6 (6 Weeks)
Secondary	Mean Equipotency Ratio of Tapentadol Compared to Fentanyl	Tapentadol was compared to Transdermal Fentanyl with Fentanyl set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Transdermal Fentanyl was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Fentanyl.	Baseline; End of Week 6 (6 Weeks)
Secondary	Mean Equipotency Ratio of Tapentadol Compared to Morphine	Tapentadol was compared to Morphine with Morphine set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Morphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Morphine.	Baseline; End of Week 6 (6 Weeks)
Secondary	Mean Equipotency Ratio of Tapentadol Compared to Hydromorphone	Tapentadol was compared to Hydromorphone with Hydromorphone set to 1. The average total daily dose of Tapentadol at which a pain score equivalent or below to the pain score at the end of observation period under Hydromorphone was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Hydromorphone.	Baseline; End of Week 6 (6 Weeks)
Secondary	painDETECT Assessment at Baseline	The painDETECT questionnaire was used to determine the possibility of the presence of a neuropathic pain component. It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".	Baseline
Secondary	painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release Treatment	The baseline painDETECT score was reassessed at the end of Week 6.; It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".	End of Week 6
Secondary	painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release Treatment	The baseline painDETECT score was reassessed at the end of Week 12.; It is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".	End of Week 12