Tapentadol in Chronic Malignant Tumour Related Pain

Phase 3

Terminated

• Conditions: Chronic Pain; Pain; Cancer
• Interventions: Drug: Tapentadol Prolonged Release

• Registration Number: NCT01264887
• Lead Sponsor: Grünenthal GmbH

Brief Summary

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.

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 Timeline

• Study First Submitted: 2010-12-16
• Study First Submitted QC: 2010-12-21
• Study First Posted: 2010-12-22
• Study Start: 2011-03
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Results First Submitted: 2015-04-30
• Results First Submitted QC: 2015-06-01
• Results First Posted: 2015-06-22
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-18
• Last Update Posted: 2019-11-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 31

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tapentadol Prolonged Release	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).

Primary Outcome Measures

Name	Time	Method
Relatedness Assessment of Treatment Emergent Adverse Events	Day 1; up to 144 weeks	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	Day 1; up to 144 weeks	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.
Severity of Adverse Events	Day 1; up to 144 weeks	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.
Time Dependence of Adverse Events	Day 1; 144 weeks	The onset and duration of TEAEs was not evaluated for this trial.

Secondary Outcome Measures

Name	Time	Method
Assess Consumption of Tapentadol During Long Term Use	Day 1; up to 144 weeks	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	Day 1; up to 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).

Trial Locations

Locations (12)

Site 359004; 🇧🇬 Shumen, Bulgaria

Site 373001; 🇲🇩 Chisinau, Moldova, Republic of

Site 036010; 🇭🇺 Szekszard, Hungary

Site 040006; 🇷🇴 Brasov, Romania

Site 040002; 🇷🇴 Bucharest, Romania

Site 381002; 🇷🇸 Nis, Serbia

Site 007012; 🇷🇺 Vladikavkaz, Russian Federation

Site 048004; 🇵🇱 Bydgoszcz, Poland

Site 048001; 🇵🇱 Warszawa, Poland

Site 036002; 🇭🇺 Nyiregyhaza, Hungary

Site 007007; 🇷🇺 Nizhniy Novgorod, Russian Federation

Site 381001; 🇷🇸 Sremska Kamenica, Serbia