Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Pain Due to Osteoarthritis Taking Either WHO Step I or Step II Analgesics or no Regular Analgesic

Chronic 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 Uncontrolled Severe Chronic Pain Due to Osteoarthritis of the Knee Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00983073
• Other study ID #: 441172
• Secondary ID: 2009-010423-58
• Status: Completed
• Phase: Phase 3
• Start date: September 2009
• Est. completion date: September 2010

Study information

• Verified date: October 2019
• 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 participants suffering from severe chronic pain due to osteoarthritis of the knee who are taking either WHO Step I or Step II analgesics or no regular analgesics. 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 (either WHO Step I or Step II analgesics or no regular analgesics) with that of tapentadol hydrochloride prolonged release (PR) treatment during defined periods of evaluation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: September 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Participants have signed an Informed Consent Form indicating that they understand the purpose of and the procedures required for the trial and are willing to participate in it.

2. 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.

3. Participants must be appropriately communicative to verbalize and to differentiate with regard to location and intensity of the pain.

4. Participants must be at least 40 years of age.

5. Participants must have a diagnosis of osteoarthritis of the knee based on the American College of Rheumatology (ACR) classification criteria:

• Knee pain and

• Radiographic osteophytes or

• Knee pain and

• Aged 40 years or above, and

• Morning stiffness of less than 30 minutes of duration and

• Crepitus on motion.

6. Participants must have pain at the reference joint which has been present for at least 3 months.

7. Participant's pain must require a strong analgesic (defined as WHO Step III) as judged by the Investigator.

8. Participants must report a rate of satisfaction with their previous analgesic regimen not exceeding "fair" on a participant satisfaction with treatment scale (5-point VRS).

9. If under regular, daily pretreatment:

• Participants must be taking a WHO Step I or Step II analgesic medication for osteoarthritis of the knee on a daily basis for at least 2 weeks prior to the Screening Visit.

• The Investigator considers dose increase of WHO Step I analgesics (as mono- or combination therapy) and/or continuation with or dose increase of WHO Step II analgesics inadequate for the individual participant, whatever applicable.

• Participants must have an average pain intensity score (NRS 3) greater than 5 points during the last 3 days prior to the Screening Visit.

OR if no regular analgesic pretreatment is reported:

• Participants must have an average pain intensity score (NRS-3)greater than 6 points in the last 3 days prior to the Screening Visit and related to osteoarthritis.

Exclusion Criteria:

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. Known history of or laboratory values reflecting severe renal impairment.

6. Known history of moderately or severely impaired hepatic function.

7. History of or active hepatitis B or C within the past 3 months or history of HIV infection.

8. History of seizure disorder or epilepsy.

9. 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.

10. Pregnant or breast-feeding.

11. History of allergy to, or hypersensitivity to tapentadol hydrochloride or its excipients, or contraindications related to tapentadol hydrochloride including:

• Participants with acute or severe bronchial asthma or hypercapnia.

• Participants who have or are suspected of having paralytic ileus.

12. 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.

13. Participation in another trial concurrently or within 4 weeks prior to the Screening Visit.

14. Known to or suspected of not being able to comply with the protocol and the use of the investigational medicinal product.

15. Use of monoamine oxidase inhibitors within 14 days before the Screening Visit.

16. Non-stable dosing of selective serotonin reuptake inhibitors within 30 days before the Screening Visit (Doses must remain stable during the trial).

17. Osteoarthritis in a flare state.

18. Use of intra-articular injections of hyaluronic acid in the reference joint within 3 months before the Screening Visit.

19. Presence of conditions other than osteoarthritis of the reference joint that could confound the assessment or self-evaluation of pain, e.g., anatomical deformities, significant skin conditions such as abscess or syndromes with widespread pain such as fibromyalgia. Participants with osteoarthritis at joints other than the reference joint will not be excluded as long as the reference joint is the source of main pain and disability.

20. History and clinical signs at the reference joint of crystal-induced (e.g., gout, pseudo-gout), metabolic, infectious and autoimmune disease.

21. Any concomitant painful condition that could interfere with the participants' trial assessments or with their ability to differentiate the current joint pain from other painful conditions.

22. Any painful procedures during the trial (e.g., major surgery, including the reference joint) that may, in the opinion of the Investigator, affect the efficacy or safety assessments.

23. Pending litigation due to chronic pain or disability.

24. Intake of Step III analgesics within the 30 days prior to the Screening Visit.

Related Conditions & MeSH terms

• Chronic Pain
• Osteoarthritis

Intervention

Drug:
• Tapentadol
Tapentadol Prolonged Release (PR) Titration and Optimal Dose Period: Starting at 50 mg Tapentadol PR twice daily, adjusting at 50 mg PR steps (upwards or downwards) as necessary to achieve a balance between pain relief and a satisfactory level of tolerability. Participants were not permitted to exceed 500 mg of Tapentadol per day. Maintenance Period: Participants continuing on the dose established in the previous period.

Locations

Country	Name	City	State
France	Site 1	Belfort
France	Site 4	Marseille
France	Site 2	Murs Erigné
France	Site 3	Nantes
Germany	Site 5	Berlin
Germany	Site 2	Köln Dünnwald
Germany	Site 4	Leipzig
Germany	Site 6	Leipzig
Germany	Site 1	Marl
Germany	Site 3	Meine
Germany	Site 8	Rudolstadt
Poland	Site 4	Lodz
Poland	Site 2	Warsawa
Spain	Site 2	A Coruna
Spain	Site 7	A Coruna
Spain	Site 6	Lugo
Spain	Site 3	Madrid
Spain	Site 1	Torrelavega
United Kingdom	Site 3	London
United Kingdom	Site 9	London
United Kingdom	Site 06	Manchester
United Kingdom	Site 08	Portsmouth
United Kingdom	Site 1	Solihull
United Kingdom	Site 4	Swansea

Sponsors (1)

Lead Sponsor	Collaborator
Grünenthal GmbH

Countries where clinical trial is conducted

France,  Germany,  Poland,  Spain,  United Kingdom, 

References & Publications (1)

Steigerwald I, Müller M, Kujawa J, Balblanc JC, Calvo-Alén J. Effectiveness and safety of tapentadol prolonged release with tapentadol immediate release on-demand for the management of severe, chronic osteoarthritis-related knee pain: results of an open-l — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Primary Endpoint is Defined as the Change From Week -1 of the Average Pain Intensity Score on an 11-point NRS-3 at Week 6.	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 to end of week 6
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 PR 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 PR 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	EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time	The participant scored the EuroQol-5. This is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. The positive values indicate that during the study the health status improved.	Baseline; End of Week 6 (6 Weeks)
Secondary	EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time	The participant scored the EuroQol-5. This is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. The positive values indicate that during the study the health status improved.	Baseline; End of Week 12 (12 Weeks)
Secondary	Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)	EuroQoL-5D Health State Visual Analog Scale (VAS) is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The values indicated represent the change from the baseline, a positive value indicates an improvement.	Baseline; End of Week 6 (6 Weeks)
Secondary	Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)	EuroQoL-5D Health State Visual Analog Scale (VAS) is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The values indicated represent the change from the baseline, a positive value indicates an improvement.	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	Clinical Global Impression of Change	In the Clinical Global Impression of Change (CGIC) the clinician indicates the perceived change over the treatment period. The clinician 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	Clinical Global Impression of Change	In the Clinical Global Impression of Change (CGIC) the clinician indicates the perceived change over the treatment period. The clinician 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	Participant's Satisfaction With Previous Analgesic Treatment	Participants were requested to rate their previous analgesic medication on a 5-point scale. Previous medication was rated as excellent, very good, good, fair and poor.	Baseline
Secondary	Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol.	Participants were requested to rate their tapentadol (new) analgesic medication on a 5-point scale. The medication was rated as excellent, very good, good, fair and poor.	Baseline; End of Week 6 (6 Weeks)
Secondary	Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol.	Participants were requested to rate their tapentadol (new) analgesic medication on a 5-point scale. The medication was rated as excellent, very good, good, fair and poor.	Baseline; End of Week 12 (12 Weeks)
Secondary	Baseline Western Ontario McMaster Questionnaire (WOMAC) Global Score Assessing Pain, Disability and Joint Stiffness of the Knee	Western Ontario McMaster Questionnaire (WOMAC) Global Score: WOMAC is measured with a Likert ordinal scale (the participant gives one of 5 possible answers) A higher score indicate that a symptom is bothersome or disabling. The WOMAC is a self-administered questionnaire and has 24 questions: Pain, Stiffness and Physical Function. The possible scores range from 0-20 for pain, 0-8 for stiffness, 0-68 for physical function and these are then summed 0-96 for the global score. A lower score indicates a lower level of symptoms and or disability.	Baseline
Secondary	Change From Baseline in the Western Ontario McMaster Questionnaire (WOMAC) Global Score Assessing Pain, Disability and Joint Stiffness of the Knee Over the Last Week at Week 6	The WOMAC is a self-administered questionnaire and has 24 questions: Pain, Stiffness and Physical Function. The possible scores range from 0-20 for pain, 0-8 for stiffness, 0-68 for physical function and these are then summed 0-96 for the global score. The negative value indicates that there has been an improvement since baseline, the higher the value the greater the change since baseline.	Baseline; End of Week 6 (6 Weeks)
Secondary	Change From Baseline in the Western Ontario McMaster Questionnaire (WOMAC) Global Score Assessing Pain, Disability and Joint Stiffness of the Knee Over the Last Week at Week 12	The WOMAC is a self-administered questionnaire and has 24 questions: Pain, Stiffness and Physical Function. The possible scores range from 0-20 for pain, 0-8 for stiffness, 0-68 for physical function and these are then summed 0-96 for the global score. The negative value indicates that there has been an improvement since baseline, the higher the value the greater the change since baseline.	Baseline; End of Week 12 (12 Weeks)