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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

Phase 3
Terminated
Conditions
Pain
Chronic Pain
Nociceptive Pain
Low Back Pain
Neuropathic Pain
Interventions
Registration Number
NCT00986258
Lead Sponsor
Grünenthal GmbH
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
136
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Tapentadol Prolonged ReleaseTapentadol Prolonged ReleaseOther Names: * Nucynta * Palexia
Primary Outcome Measures
NameTimeMethod
Number of Participants That Responded to Treatment6 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Average Pain Intensity Before the Start of Tapentadol TreatmentBaseline

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".

Change in Average Pain Intensity After 6 Weeks of Tapentadol Prolonged Release Treatment.Baseline; End of Week 6 (6 weeks)

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.

Change in Average Pain Intensity After 12 Weeks of Tapentadol Prolonged Release Treatment.Baseline; End of Week 12 (12 weeks)

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.

Patient Global Impression of ChangeBaseline; End of Week 12 (12 Weeks)

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.

Change in the Health Survey Scores Form (SF-36)Baseline; End of Week 12 (12 Weeks)

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.

Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall ScoreEnd of Week 12

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).

Mean Equipotency Ratio of Tapentadol Compared to OxycodoneBaseline; End of Week 6 (6 Weeks)

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.

Mean Equipotency Ratio of Tapentadol Compared to BuprenorphineBaseline; End of Week 6 (6 Weeks)

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.

Mean Equipotency Ratio of Tapentadol Compared to FentanylBaseline; End of Week 6 (6 Weeks)

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.

Mean Equipotency Ratio of Tapentadol Compared to MorphineBaseline; End of Week 6 (6 Weeks)

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.

Mean Equipotency Ratio of Tapentadol Compared to HydromorphoneBaseline; End of Week 6 (6 Weeks)

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.

painDETECT Assessment at BaselineBaseline

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".

painDETECT Assessment for Participants After 6 Weeks of Tapentadol Prolonged Release TreatmentEnd of Week 6

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".

painDETECT Assessment for Participants After 12 Weeks of Tapentadol Prolonged Release TreatmentEnd of Week 12

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".

Trial Locations

Locations (27)

BE004

🇧🇪

Brugge, Belgium

PL002

🇵🇱

Krakow, Poland

CH002

🇨🇭

St. Gallen, Switzerland

DE003

🇩🇪

Berlin, Germany

NL001

🇳🇱

Tiel, Netherlands

NL003

🇳🇱

Eindhoven, Netherlands

DE004

🇩🇪

Leipzig, Germany

DE008

🇩🇪

Leipzig, Germany

BE002

🇧🇪

Edegem, Belgium

FR004

🇫🇷

Thionville, France

FR001

🇫🇷

Toulouse, France

NL002

🇳🇱

Alkmaar, Netherlands

ES003

🇪🇸

Malaga, Spain

ES004

🇪🇸

Sevilla, Spain

ES006

🇪🇸

Cadiz, Spain

DE005

🇩🇪

Albstadt, Germany

NL004

🇳🇱

Doetinchem, Netherlands

DE006

🇩🇪

Kiel, Germany

DE007

🇩🇪

Stuttgart, Germany

PL001

🇵🇱

Poznan, Poland

CZ001

🇨🇿

Brno, Czechia

BE003

🇧🇪

Charleroi, Belgium

DE001

🇩🇪

Berlin, Germany

ES001

🇪🇸

Granada, Spain

ES005

🇪🇸

Valencia, Spain

CH001

🇨🇭

Basel, Switzerland

BE001

🇧🇪

Liège, Belgium

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