Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Tapentadol in Chronic Malignant Tumour Related Pain

This study has been terminated.
(Administrative reasons)
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT01264887
First received: December 16, 2010
Last updated: June 1, 2015
Last verified: June 2015
  Purpose
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.

Condition Intervention Phase
Cancer
Chronic Pain
Pain
Drug: Tapentadol Prolonged Release
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Single-arm, Flexible Dosing, Phase III Trial, With Oral Tapentadol Prolonged Release (PR) in Subjects With Chronic Malignant Tumor-related Pain Who Have Completed the Maintenance Period of the KF5503/15 Trial.

Resource links provided by NLM:


Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • Severity of Adverse Events [ Time Frame: Day 1; up to 144 weeks ] [ Designated as safety issue: Yes ]

    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.


  • Relatedness Assessment of Treatment Emergent Adverse Events [ Time Frame: Day 1; up to 144 weeks ] [ Designated as safety issue: Yes ]
    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".

  • Countermeasures Taken Due to Treatment Emergent Adverse Events [ Time Frame: Day 1; up to 144 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Time Dependence of Adverse Events [ Time Frame: Day 1; 144 weeks ] [ Designated as safety issue: Yes ]
    The onset and duration of TEAEs was not evaluated for this trial.


Secondary Outcome Measures:
  • Assess Consumption of Tapentadol During Long Term Use [ Time Frame: Day 1; up to 144 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Tapentadol Prolonged Release Exposure [ Time Frame: Day 1; up to 144 weeks ] [ Designated as safety issue: No ]
    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).


Other Outcome Measures:
  • Average Pain Intensity (Over a Twelve-week Period) [ Time Frame: Day 1; up to Week 144 ] [ Designated as safety issue: No ]

    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.


  • Average Daily Total Tapentadol Prolonged Release Dose [ Time Frame: Day 1; up to 144 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: March 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tapentadol Prolonged Release
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).
Drug: Tapentadol Prolonged Release
Titration to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerates and wishes to continue treatment.
Other Names:
  • Nucynta®
  • Palexia®
  • Yantil®

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have signed an Informed Consent Form.
  • At least 18 years of age.
  • Male and non-pregnant, non-lactating female subjects. Sexually active women must be post menopausal, surgically sterile, or practicing an effective method of birth control before entry and throughout the trial. Female participants of child-bearing potential must have a negative pregnancy test at enrollment.
  • Within 24 weeks of either full completion or completion of the double-blind treatment period (Visit 8) of KF5503/15 trial performed in participants with moderate to severe chronic malignant tumor related pain.
  • Participant is, in the opinion of the investigator, expected to continue to have an overall positive benefit/risk ratio from continuing analgesic treatment within this trial.
  • Participant must be willing to take tapentadol prolonged release (PR) throughout their participation in the trial.

Exclusion Criteria:

  • History of alcohol and/or drug abuse.
  • The participant has a clinically significant disease other than cancer that in the Investigator's opinion may affect the safety of the participant.
  • Employees of the investigator or trial center or family members of the employees or the investigator.
  • Known to or suspected of not being able to comply with the protocol and the use of tapentadol prolonged release (PR).
  • Concurrent participation in another trial (except for participation in the KF5503/15 trial) or planning to be enrolled in another clinical trial during the course of this trial.
  • Previous participation in another trial between the end of KF5503/15 and enrollment into the current trial, KF5503/52.
  • History of seizure disorder, epilepsy, traumatic brain injury, stroke or transient ischemic attack.
  • Known history and/or presence of cerebral tumors or metastases.
  • Rapidly escalating pain or pain uncontrolled by therapy and was previously treated with maximum dose level of Investigational Medicinal Product.
  • Participant is taking any prohibited concomitant medications.
  • Uncontrolled hypertension.
  • Known moderate or severe hepatic impairment.
  • Known severe renal impairment.
  • Clinically relevant history of hypersensitivity, allergy, or contraindications to tapentadol or its excipients.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01264887

Locations
Bulgaria
Site 359004
Shoumen, Bulgaria, 9700
Hungary
Site 036002
Nyiregyhaza, Hungary, 4412
Site 036010
Szekszard, Hungary, 7100
Moldova, Republic of
Site 373001
Chisinau, Moldova, Republic of, 2025
Poland
Site 048004
Bydgoszcz, Poland, 85796
Site 048001
Warszawa, Poland, 02781
Romania
Site 040006
Brasov, Romania, 500074
Site 040002
Bucharest, Romania, 022328
Russian Federation
Site 007007
Nizhniy Novgorod, Russian Federation, 603140
Site 007012
Vladikavkaz, Russian Federation, 362007
Serbia
Site 381002
Nis, Serbia, 18000
Site 381001
Sremska Kamenica, Serbia, 21204
Sponsors and Collaborators
Grünenthal GmbH
Investigators
Principal Investigator: Hans-Georg Kress, Prof. Dr. med General Hospital Vienna
  More Information

Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT01264887     History of Changes
Other Study ID Numbers: KF5503/52  2009-013291-46  168935 
Study First Received: December 16, 2010
Results First Received: April 30, 2015
Last Updated: June 1, 2015
Health Authority: Austria: Agency for Health and Food Safety
Bulgaria: Bulgarian Drug Agency
Croatia: Ministry of Health and Social Care
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Moldova: Medicines Agency
Poland: The Central Register of Clinical Trials
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Serbia: Medicines and Medical Devices Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Grünenthal GmbH:
analgesia
analgesics
chronic pain
tumour related pain
chronic malignant tumor-related pain

Additional relevant MeSH terms:
Chronic Pain
Neoplasms
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on December 02, 2016