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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionChronic Pain
Osteoarthritis
InterventionDrug: Tapentadol
PhasePhase 3
SponsorGrünenthal GmbH
Responsible PartyGrünenthal GmbH
ClinicalTrials.gov IdentifierNCT00983073
First ReceivedSeptember 21, 2009
Last UpdatedFebruary 4, 2013
Last verifiedFebruary 2013

Tracking Information[ + expand ][ + ]

First Received DateSeptember 21, 2009
Last Updated DateFebruary 4, 2013
Start DateSeptember 2009
Estimated Primary Completion DateSeptember 2010
Current Primary Outcome MeasuresThe 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. [Time Frame: Baseline to end of week 6] [Designated as safety issue: No]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.
Current Secondary Outcome Measures
  • Average Pain Intensity Before the Start of Tapentadol Treatment [Time Frame: Baseline] [Designated as safety issue: No]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 PR Treatment [Time Frame: Baseline; End of Week 6 (6 Weeks)] [Designated as safety issue: No]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 PR Treatment [Time Frame: Baseline; End of Week 12 (12 Weeks)] [Designated as safety issue: No]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.
  • EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time [Time Frame: Baseline; End of Week 6 (6 Weeks)] [Designated as safety issue: No]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.
  • EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time [Time Frame: Baseline; End of Week 12 (12 Weeks)] [Designated as safety issue: No]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.
  • Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) [Time Frame: Baseline; End of Week 6 (6 Weeks)] [Designated as safety issue: No]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.
  • Change in Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) [Time Frame: Baseline, End of Week 12 (12 Weeks)] [Designated as safety issue: No]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.
  • Patient Global Impression of Change [Time Frame: Baseline; End of Week 6 (6 Weeks)] [Designated as safety issue: No]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.
  • Patient Global Impression of Change [Time Frame: Baseline; End of Week 12 (12 Weeks)] [Designated as safety issue: No]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.
  • Clinical Global Impression of Change [Time Frame: Baseline; End of Week 6 (6 Weeks)] [Designated as safety issue: No]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.
  • Clinical Global Impression of Change [Time Frame: Baseline; End of Week 12 (12 Weeks)] [Designated as safety issue: No]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.
  • Participant's Satisfaction With Previous Analgesic Treatment [Time Frame: Baseline] [Designated as safety issue: No]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.
  • Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol. [Time Frame: Baseline; End of Week 6 (6 Weeks)] [Designated as safety issue: No]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.
  • Participant's Satisfaction With New Analgesic Treatment, i.e Tapentadol. [Time Frame: Baseline; End of Week 12 (12 Weeks)] [Designated as safety issue: No]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 Western Ontario McMaster Questionnaire (WOMAC) Global Score Assessing Pain, Disability and Joint Stiffness of the Knee [Time Frame: Baseline] [Designated as safety issue: No]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.
  • 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 [Time Frame: Baseline; End of Week 6 (6 Weeks)] [Designated as safety issue: No]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.
  • 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 [Time Frame: Baseline; End of Week 12 (12 Weeks)] [Designated as safety issue: No]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.

Descriptive Information[ + expand ][ + ]

Brief TitleEvaluation 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
Official TitleAn 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.
Brief 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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Chronic Pain
  • Osteoarthritis
InterventionDrug: 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.
Other Names:
  • Nucynta
  • Palexia
Study Arm (s)Experimental: Tapentadol
Tapentadol PR was given orally twice a day. A maximum of 2 oral Tapentadol IR tablets per day, with a minimum of a 4 hour interval between doses, were taken if there were acute pain episodes. The total daily dose of Tapentadol PR and IR were not permitted to exceed 500 mg per day.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment224
Estimated Completion DateSeptember 2010
Estimated Primary Completion DateJune 2010
Eligibility Criteria
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.
GenderBoth
Ages40 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesFrance, Germany, Poland, Spain, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00983073
Other Study ID Numbers441172
Has Data Monitoring CommitteeNo
Information Provided ByGrünenthal GmbH
Study SponsorGrünenthal GmbH
CollaboratorsNot Provided
Investigators Principal Investigator: Jaime Calvo, Dr. MD Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria Santander, Spain
Verification DateFebruary 2013

Locations[ + expand ][ + ]

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