Tapentadol in Chronic Malignant Tumour Related Pain

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.

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.

Study Overview

• Status: Terminated
• Conditions: Pain; Cancer; Chronic Pain
• Intervention / Treatment: Drug: Tapentadol Prolonged Release

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).

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Shumen, Bulgaria, 9700
    • Site 359004
• Hungary
  • Nyiregyhaza, Hungary, 4412
    • Site 036002
  • Szekszard, Hungary, 7100
    • Site 036010
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • Site 373001
• Poland
  • Bydgoszcz, Poland, 85796
    • Site 048004
  • Warszawa, Poland, 02781
    • Site 048001
• Romania
  • Brasov, Romania, 500074
    • Site 040006
  • Bucharest, Romania, 022328
    • Site 040002
• Russian Federation
  • Nizhniy Novgorod, Russian Federation, 603140
    • Site 007007
  • Vladikavkaz, Russian Federation, 362007
    • Site 007012
• Serbia
  • Nis, Serbia, 18000
    • Site 381002
  • Sremska Kamenica, Serbia, 21204
    • Site 381001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Palexia®; Nucynta®; Yantil®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.	Day 1; 144 weeks

Secondary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Grünenthal GmbH
• Investigators: Principal Investigator: Hans-Georg Kress, Prof. Dr. med, General Hospital Vienna

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: December 16, 2010
• First Submitted That Met QC Criteria: December 21, 2010
• First Posted (ESTIMATE): December 22, 2010

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: chronic pain; analgesia; analgesics; tumour related pain; chronic malignant tumor-related pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Neoplasms; Chronic Pain; Cancer Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Tapentadol
• Other Study ID Numbers: KF5503/52; 2009-013291-46 (EUDRACT_NUMBER); 168935 (OTHER: Grünenthal GmbH)