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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-013291-46 | EudraCT Number | ||
| 168935 | Other Identifier | Grünenthal GmbH |
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Administrative reasons
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The purpose of this trial is the characterization of the long term safety profile and long-term dose requirements of tapentadol PR (prolonged release) in patients with malignant tumor-related pain. In the United States the prolonged-release formulation is also referred to as the extended-release formulation.
The prevalence of tumor-related pain is high and the treatment of chronic tumor-related pain remains a challenging therapeutic problem.
Participants directly entering the KF5503/52 trial from the KF5503/15 trial (i.e., within 7 days of Visit 8 of the KF5503/15 trial) is scheduled: a Transfer Visit, an Open-label Treatment Period and a Follow-up Period.
For participants with a gap of more than 7 days and less than 24 weeks, between their full completion of the KF5503/15 trial and entry into the KF5503/52 trial the following is scheduled: an Enrollment Visit, an Entry Visit for assessment of eligibility, an Open-label Treatment Period and a Follow-up Period.
This trial was designed to offer patients with chronic malignant tumor-related pain the option of continuing treatment by receiving tapentadol prolonged release (PR).
The protocol scheduled visits every 28 days during the open-label treatment period. Unscheduled visits (or at least unscheduled telephone calls) were planned when dose adjustment is required. If a visit is not possible at the time of dose change, it could be done up to 7 days later. Unscheduled visits could also be performed whenever considered necessary (i.e., for evaluation of adverse events).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tapentadol Prolonged Release | Experimental | Participants allocated to this treatment arm can be flexibly dosed between 100 to 250 mg tapentadol twice daily (50 and 100 mg tablets to be dispensed). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tapentadol Prolonged Release | Drug | Titration to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerates and wishes to continue treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Severity of Adverse Events | The severity of treatment emergent adverse events was any untoward medical occurrence in a patient administered tapentadol. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of the (investigational) medicinal product whether or not related to the use of tapentadol. The clinical "intensity" of adverse event were classified as: Mild: signs and symptoms which can be easily tolerated. Symptoms could be ignored and disappeared when the participant is distracted. Moderate: symptoms caused discomfort but were tolerable, they could not be ignored and affect concentration. Severe: symptoms affected the usual daily activity. | Day 1; up to 144 weeks |
| Relatedness Assessment of Treatment Emergent Adverse Events | Participant-based analysis of treatment emergent adverse events (TEAEs) regarding the relationship to the study drug (tapentadol). The TEAEs were reported by the participants or were captured by the investigator. The relationship was rated by the investigator. The categorization of relatedness into one of the two categories was based on the following: Related included "possible", "probable/likely", and "certain"; whilst unrelated treatment emergent adverse events include those rated by the investigator as "unlikely", "conditional/unclassified", "un-assessable/unclassifiable", and "not related". | Day 1; up to 144 weeks |
| Countermeasures Taken Due to Treatment Emergent Adverse Events | Participant-based analysis of treatment emergent adverse events (TEAEs) regarding countermeasure to the study drug (tapentadol). The TEAEs were reported by the participants or were captured by the investigator. The countermeasure taken by the investigator were reported. | Day 1; up to 144 weeks |
| Time Dependence of Adverse Events | The onset and duration of TEAEs was not evaluated for this trial. |
| Measure | Description | Time Frame |
|---|---|---|
| Assess Consumption of Tapentadol During Long Term Use | Summary of the modal total daily dose during the treatment period. The modal dose was based on assessment of the consecutive morning and evening intake amounts on each day and evaluation of the total daily dose. | Day 1; up to 144 weeks |
| Tapentadol Prolonged Release Exposure |
| Measure | Description | Time Frame |
|---|---|---|
| Average Pain Intensity (Over a Twelve-week Period) | The participant scored their pain intensity 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". Average pain intensity score is the average of pain experienced for previous 24 hours as rated on an 11-point NRS at each visit. Calculations are based on 3 consecutive planned (at 4-weekly intervals) visits. All available data of a participant was used; if a participant dropped-out or had incomplete data during a 12-week period no imputations were performed for the missing values. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hans-Georg Kress, Prof. Dr. med | General Hospital Vienna | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Site 359004 | Shumen | 9700 | Bulgaria | |||
| Site 036002 |
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First participant was enrolled on the 03 March 2011 and the last participant completed the trial on the 08 May 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tapentadol Prolonged Release | All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tapentadol Prolonged Release | All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Severity of Adverse Events | The severity of treatment emergent adverse events was any untoward medical occurrence in a patient administered tapentadol. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of the (investigational) medicinal product whether or not related to the use of tapentadol. The clinical "intensity" of adverse event were classified as: Mild: signs and symptoms which can be easily tolerated. Symptoms could be ignored and disappeared when the participant is distracted. Moderate: symptoms caused discomfort but were tolerable, they could not be ignored and affect concentration. Severe: symptoms affected the usual daily activity. | Safety Set. | Posted | Number | participants | Day 1; up to 144 weeks |
|
One participant was treated up to 144 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tapentadol Prolonged Release | All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Non-systematic Assessment | Treatment emergent event leading to death |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (17.0) | Non-systematic Assessment |
The trial was stopped for administrative reasons. Three years after trial initiation 2 participants were in the trial and to permit analysis and reporting the sponsor decided to terminate the trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director Clinical Trials | Grünenthal GmbH | +49 241 569 | 3223 | clinical-trials@grunenthal.com |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D059350 | Chronic Pain |
| D010146 | Pain |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010468 | Perceptual Disorders |
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| ID | Term |
|---|---|
| D000077432 | Tapentadol |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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|
| Day 1; 144 weeks |
The number of days that participants took tapentadol prolonged release. The extent of exposure was categorized into 2 periods, less than 90 days and more than 90 days (up to 144 weeks). |
| Day 1; up to 144 weeks |
| Day 1; up to Week 144 |
| Average Daily Total Tapentadol Prolonged Release Dose | The Total Daily Dose (TDD) on any given day is the sum of the morning and evening intake amounts. The average TDD is an individuals average over the trial period. | Day 1; up to 144 weeks |
| Nyíregyháza |
| 4412 |
| Hungary |
| Site 036010 | Szekszárd | 7100 | Hungary |
| Site 373001 | Chisinau | 2025 | Moldova |
| Site 048004 | Bydgoszcz | 85796 | Poland |
| Site 048001 | Warsaw | 02781 | Poland |
| Site 040006 | Brasov | 500074 | Romania |
| Site 040002 | Bucharest | 022328 | Romania |
| Site 007007 | Nizhny Novgorod | 603140 | Russia |
| Site 007012 | Vladikavkaz | 362007 | Russia |
| Site 381001 | Kamenitz | 21204 | Serbia |
| Site 381002 | Niš | 18000 | Serbia |
| Physician Decision |
|
| Withdrawal by Subject |
|
| Sponsor Decision Administrative Reasons |
|
| Other |
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Pain type | A participant could be suffering from more than one type of pain. The participant was counted in more than one category and therefore the addition of numbers are higher than the number of participants. | Number | participants |
|
All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
|
|
| Secondary | Assess Consumption of Tapentadol During Long Term Use | Summary of the modal total daily dose during the treatment period. The modal dose was based on assessment of the consecutive morning and evening intake amounts on each day and evaluation of the total daily dose. | The modal dose is based on assessment of the consecutive morning and evening intake amounts on each day and evaluation of the total daily dose. No participant received more than 500 mg per day. | Posted | Number | participants | Day 1; up to 144 weeks |
|
|
|
| Primary | Relatedness Assessment of Treatment Emergent Adverse Events | Participant-based analysis of treatment emergent adverse events (TEAEs) regarding the relationship to the study drug (tapentadol). The TEAEs were reported by the participants or were captured by the investigator. The relationship was rated by the investigator. The categorization of relatedness into one of the two categories was based on the following: Related included "possible", "probable/likely", and "certain"; whilst unrelated treatment emergent adverse events include those rated by the investigator as "unlikely", "conditional/unclassified", "un-assessable/unclassifiable", and "not related". | Safety Set. | Posted | Number | participants | Day 1; up to 144 weeks |
|
|
|
| Primary | Countermeasures Taken Due to Treatment Emergent Adverse Events | Participant-based analysis of treatment emergent adverse events (TEAEs) regarding countermeasure to the study drug (tapentadol). The TEAEs were reported by the participants or were captured by the investigator. The countermeasure taken by the investigator were reported. | Safety Set. | Posted | Number | participants | Day 1; up to 144 weeks |
|
|
|
| Other Pre-specified | Average Pain Intensity (Over a Twelve-week Period) | The participant scored their pain intensity 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". Average pain intensity score is the average of pain experienced for previous 24 hours as rated on an 11-point NRS at each visit. Calculations are based on 3 consecutive planned (at 4-weekly intervals) visits. All available data of a participant was used; if a participant dropped-out or had incomplete data during a 12-week period no imputations were performed for the missing values. | Safety Set. | Posted | Mean | Standard Deviation | units on a scale | Day 1; up to Week 144 |
|
|
|
| Other Pre-specified | Average Daily Total Tapentadol Prolonged Release Dose | The Total Daily Dose (TDD) on any given day is the sum of the morning and evening intake amounts. The average TDD is an individuals average over the trial period. | Safety Set. | Posted | Mean | Standard Deviation | mg per day | Day 1; up to 144 weeks |
|
|
|
| Secondary | Tapentadol Prolonged Release Exposure | The number of days that participants took tapentadol prolonged release. The extent of exposure was categorized into 2 periods, less than 90 days and more than 90 days (up to 144 weeks). | Safety Set. | Posted | Number | participants | Day 1; up to 144 weeks |
|
|
|
| Primary | Time Dependence of Adverse Events | The onset and duration of TEAEs was not evaluated for this trial. | No evaluation was performed. | Posted | Day 1; 144 weeks |
|
|
| 14 |
| 31 |
| 30 |
| 31 |
|
| azotaemia | Renal and urinary disorders | MedDRA (17.0) | Non-systematic Assessment | Treatment emergent event leading to death |
|
| hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Non-systematic Assessment | Investigator indicated that the progression of the underlying malignancy (lung carcinoma) was associated with the hypoxia. Treatment emergent event leading to death. |
|
| malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Non-systematic Assessment | Treatment emergent event leading to death |
|
| breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Non-systematic Assessment | Treatment emergent event leading to death |
|
| metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Non-systematic Assessment |
|
| anaemia | Blood and lymphatic system disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| cholecystitis | Hepatobiliary disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| pneumonia | Infections and infestations | MedDRA (17.0) | Non-systematic Assessment |
|
| cardiac failure | Cardiac disorders | MedDRA (17.0) | Non-systematic Assessment | Post-treatment adverse event leading to death 30 days after the last administration of tapentadol PR. The participant did not have another serious adverse event. |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (17.0) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (17.0) | Non-systematic Assessment |
|
| malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Non-systematic Assessment |
|
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Non-systematic Assessment |
|
| neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Non-systematic Assessment |
|
| nausea | Gastrointestinal disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| constipation | Gastrointestinal disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| abdominal pain upper | Gastrointestinal disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| pyrexia | General disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| ascites | Gastrointestinal disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| general physical health deterioration | General disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| fatigue | General disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| dizziness | Nervous system disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| headache | Nervous system disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| somnolence | Nervous system disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| sinus tachycardia | Cardiac disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| tachycardia | Cardiac disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| bronchitis | Infections and infestations | MedDRA (17.0) | Non-systematic Assessment |
|
| urinary tract infection | Infections and infestations | MedDRA (17.0) | Non-systematic Assessment |
|
| pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Non-systematic Assessment |
|
| haematuria | Renal and urinary disorders | MedDRA (17.0) | Non-systematic Assessment |
|
The Sponsor reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| Title | Measurements |
|---|---|
|
| 300 to less than 350 mg/day |
|
| 350 to less than 400 mg/day |
|
| 400 to less than 450 mg/day |
|
| 450 to less than 500 mg/day |
|
| 500 mg/day |
|
| Title | Measurements |
|---|---|
|
| Investigator-rated Not Related |
|
| Title | Measurements |
|---|---|
|
| Countermeasures with Medication |
|
| Trial Discontinued Countermeasure |
|
| Other Countermeasure due to Somnolence |
|
| Other Countermeasure due to Migraine |
|
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| Week 13 to 24 |
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| Week 25 to 36 |
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| Week 37 to 48 |
|
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| Week 49 to 60 |
|
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| Week 61 to 72 |
|
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| Week 73 to 84 |
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| Week 85 to 96 |
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| Week 97 to 108 |
|
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| Week 109 to 120 |
|
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| Week 121 to 132 |
|
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| Week 133 to 144 |
|
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