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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00982280




Registration number
NCT00982280
Ethics application status
Date submitted
22/09/2009
Date registered
23/09/2009
Date last updated
18/10/2019

Titles & IDs
Public title
Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Pain Due to Osteoarthritis Taking WHO Step III Analgesics But Showing a Lack of Tolerability.
Scientific 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 Pain Due to Osteoarthritis of the Knee Taking WHO Step III Analgesics But Showing a Lack of Tolerability.
Secondary ID [1] 0 0
2009-010425-39
Secondary ID [2] 0 0
847022
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Pain 0 0
Osteoarthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Neurological 0 0 0 0
Other neurological disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tapentadol PR

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.


Treatment: Drugs: Tapentadol PR
Tapentadol Prolonged Release (PR) Titration and Optimal Dose Period: Starting at 50 mg, 100 mg or 150 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Responder Rate - Participants were considered responders if they reported the same or less average pain intensity over a 3 day period after 6 weeks of tapentadol PR treatment as with their previous analgesic treatment.
Timepoint [1] 0 0
6 weeks
Secondary outcome [1] 0 0
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".
Timepoint [1] 0 0
Baseline
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline; Week 6 (6 weeks)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline; Week 12 (12 weeks)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
6 weeks
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
12 weeks
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
6 weeks
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
12 weeks
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
6 Weeks
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
12 Weeks
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline; End of Week 6 (6 Weeks)
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline; End of Week 12 (12 Weeks)
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline; End of Week 6 (6 Weeks)
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Baseline; End of Week 12 (12 Weeks)
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Baseline
Secondary outcome [16] 0 0
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.
Timepoint [16] 0 0
After 6 weeks
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
After 12 weeks
Secondary outcome [18] 0 0
Mean Equipotency Ratio of Tapentadol Compared to Buprenorphine - Tapentadol was compared to Transdermal 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 Transdermal Buprenorphine was reached was documented as the equipotent or equianalgesic dose to the total daily dose of the previously used Transdermal Buprenorphine.
Timepoint [18] 0 0
Baseline; End of Week 6 (6 Weeks)
Secondary outcome [19] 0 0
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.
Timepoint [19] 0 0
Baseline; End of Week 6 (6 Weeks)

Eligibility
Key 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 40 years of age.

- 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.

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

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

- Participant must be taking a WHO Step III analgesic on a daily basis for at least 2
weeks prior to the Screening Visit.

- Participant must have responded to the WHO Step III analgesic, i.e., participant must
have a confirmed average pain intensity score (NRS 3) of smaller or equal to 5 points
during the last 3 days prior to the Screening Visit.

- Participant must report opioid-related side effects as the reason to change their
analgesic

- Participant must report a rate of satisfaction with their previous analgesic regimen
not exceeding "fair" on a subject satisfaction with treatment scale (5-point VRS).
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 thereof 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:

- participants with acute or severe bronchial asthma or hypercapnia.

- participants 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).

- Osteoarthritis in a flare state.

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

- Presence of conditions other than OA 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.
Subjects with OA 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.

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

- 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.

- Pending litigation due to chronic pain or disability.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Site 4 - Melbourne
Recruitment hospital [2] 0 0
Site 2 - Perth
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Denmark
State/province [1] 0 0
Aalborg
Country [2] 0 0
Denmark
State/province [2] 0 0
Hvidovre
Country [3] 0 0
Denmark
State/province [3] 0 0
Kolding
Country [4] 0 0
Denmark
State/province [4] 0 0
Odense
Country [5] 0 0
Denmark
State/province [5] 0 0
Vejle
Country [6] 0 0
Germany
State/province [6] 0 0
Berlin
Country [7] 0 0
Germany
State/province [7] 0 0
Katzhütte
Country [8] 0 0
Germany
State/province [8] 0 0
Leer
Country [9] 0 0
Germany
State/province [9] 0 0
Leipzig
Country [10] 0 0
Germany
State/province [10] 0 0
Zerbst
Country [11] 0 0
Poland
State/province [11] 0 0
Lublin
Country [12] 0 0
Poland
State/province [12] 0 0
Ostrow Mazowiecka
Country [13] 0 0
Poland
State/province [13] 0 0
Tychy
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
Spain
State/province [15] 0 0
Valencia
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Birmingham
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Carmarthen
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Leeds
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Middlesborough
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Oxford
Country [22] 0 0
United Kingdom
State/province [22] 0 0
York

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Grünenthal GmbH
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The main objective of the study is to evaluate the effectiveness, tolerability, and safety of
tapentadol hydrochloride prolonged release (PR) in participants suffering from severe chronic
pain due to osteoarthritis of the knee 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 PR treatment during
defined periods of evaluation.
Trial website
https://clinicaltrials.gov/show/NCT00982280
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Barbara Hoggart, Dr. MD
Address 0 0
FRCA, FRCAPM Heart of England NHS Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00982280