Clinical trial NCT02031432: CORAL XT - Open-label Extension Trial of the CORAL Trial
Official title: An Open-label, Multi-site Trial to Describe the Safety and Tolerability of Oral Cebranopadol Administered for 26 Weeks in Subjects With Cancer-related Pain Who Have Completed Treatment in the KF6005/07 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Neoplasms
Chronic Pain
Keywords: cancer-related pain
cebranopadol
Lead sponsor: Tris Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2014-01-09
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial was to find out how well cebranopadol is tolerated and how often, and which, adverse reactions occur when it is taken every day for a longer period of time. In addition, information was collected how cebranopadol affects pain and well-being in patients suffering from cancer-related pain.

Detailed description: The trial consisted of 3 phases: Titration Phase, Maintenance Phase, and Follow-Up. The total duration of the trial was approximately 28 weeks for each individual participant, including the Follow-up. The participants received cebranopadol for a maximum of approximately 26 weeks.

Eligibility criteria: Inclusion Criteria:

* Informed consent signed indicating that the participant understands the purpose of and procedures required for the trial and is willing to participate in the trial.
* Participants must be at least 18 years of age at the Enrollment Visit.
* Women of childbearing potential must have a negative pregnancy test at enrollment and must not be lactating at the Enrollment Visit.
* Participants must be willing to use medically acceptable and highly effective methods of birth control.
* Participants who have completed treatment in KF6005/07 and are still in need of around-the-clock pain analgesia with strong opioids.

Exclusion Criteria:

* The participant has a clinically significant disease or condition other than cancer which in the investigator's opinion may affect efficacy or safety assessments.
* Known to or suspected of not being able to comply with the protocol and the use of cebranopadol.
* Participants taking forbidden concomitant medications or not being able to follow the rules of use of concomitant treatment.
* History of torsade de pointes and/or presence of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, bradycardia).
* Concurrent participation in another trial (except participation in KF6005/07) or planning to be enrolled in another clinical trial (i.e., administration of experimental treatment in another clinical trial) during the course of this trial, or previous participation in this trial.
* Employees of the sponsor, investigator, or trial site or family members of the employees, sponsor, or investigator.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Event (TEAEs)
timeFrame: Up to 28 weeks (26 weeks of cebranopadol treatment and 2 weeks follow up after the last dose)
Secondary outcomes:
measure: Intensity of Treatment Emergent Adverse Events
timeFrame: Up to 28 weeks (26 weeks of cebranopadol treatment and 2 weeks follow-up after the last dose)
measure: Changes From Baseline in the Average Pain Intensity in the Last Week During the Treatment Period
timeFrame: Baseline Visit (Day 1) to End of Treatment Visit (up to 26 weeks).
Other outcomes:
measure: Outcome of Treatment Emergent Adverse Events (TEAE)
timeFrame: Baseline (Day 2) to End of trial (i.e., up to Week 28)
measure: Time to Onset of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 2) to End of trial (up to Week 28)
measure: Duration of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 2) to End of trial (up to Week 28)
measure: Causal Relationship of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 2) to End of trial (up to Week 28)
measure: Countermeasures Taken for Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 2) to End of trial (up to Week 28)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Related to Cebranopadol
timeFrame: Baseline (Day 2) to End of trial (up to Week 28)
measure: Columbia-Suicide Severity Rating Scale (C-SSRS) Scores
timeFrame: Baseline (Day 1) to End of trial (up to Week 28)
measure: Mean Scores of Chronic Pain Sleep Inventory (CPSI) and Changes From Baseline
timeFrame: Baseline (Day 1); End of Treatment (up to Week 26)
measure: Weekly Means of Daily Average Pain Intensity During the First Month of Treatment
timeFrame: Baseline (Day 1); Titration Weeks 1 and 2; Maintenance Weeks 1 and 2
measure: Worst Pain Intensity in the Last Week of Treatment (Week 26)
timeFrame: Baseline (Day 1); End of Treatment (Week 26)
measure: Weekly Average Number of Breakthrough Pain Episodes
timeFrame: Baseline (Day 1); End of Treatment (Week 26)
measure: Mean Scores of Neuropathic Pain Symptom Inventory (NPSI)
timeFrame: Baseline (Day 1); Weeks 2, 6, 14, 18; End of Treatment (up to Week 26)
measure: EuroQol-5 Dimension (EQ-5D) Health Status Index Outcome
timeFrame: Baseline (Day 1); End of Treatment (up to Week 26)
measure: EuroQol-5 Dimension (EQ-5D) Health Questionnaire - Visual Analog Scale (VAS)
timeFrame: Baseline (Day 1); End of Treatment (up to Week 26)
measure: Patient Global Impression of Change (PGIC)
timeFrame: Baseline (Day 1); End of Treatment (up to Week 26)
measure: Clinical Global Impression of Change (CGIC)
timeFrame: Baseline (Day 1); End of Treatment Visit (up to Week 26)
measure: Use of On-demand Opioid Analgesic Medication
timeFrame: From Day 3 to End of Treatment (up to Week 26) (13 time points)
measure: Mean Equipotency Ratio of Morphine Sulfate Prolonged Release Compared to Cebranopadol.
timeFrame: Baseline (Day 1); End of first month of treatment
measure: Mean Eastern Cooperative Oncology Group Performance Status (ECOG) Scores
timeFrame: From Baseline (Day 1) through to End of treatment (up to Week 26) (9 time points)
Locations:
city: Vienna
country: Austria
facility: AT004
city: Sint-Niklaas
country: Belgium
facility: BE001
city: Shumen
country: Bulgaria
facility: BG001
city: Sofia
country: Bulgaria
facility: BG008
city: Sofia
country: Bulgaria
facility: BG003
city: Sofia
country: Bulgaria
facility: BG004
city: Aalborg
country: Denmark
facility: DK006
city: Herlev
country: Denmark
facility: DK004
city: Böhlen
country: Germany
facility: DE008
city: Munich
country: Germany
facility: DE010
city: Nyiregyhaza
country: Hungary
facility: HU011
city: Będzin
country: Poland
facility: PL012
city: Dąbrowa Górnicza
country: Poland
facility: PL014
city: Gdansk
country: Poland
facility: PL003
city: Gliwice
country: Poland
facility: PL010
city: Cluj-Napoca
country: Romania
facility: RO002
city: Belgrade
country: Serbia
facility: RS003
city: Sremska Kamenica
country: Serbia
facility: RS002
city: Zrenjanin
country: Serbia
facility: RS005
city: Bratislava
country: Slovakia
facility: SK004
city: Presov
country: Slovakia
facility: SK001
city: Pruské
country: Slovakia
facility: SK005
Study officials:
affiliation: Grünenthal GmbH
name: Director Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Koch ED, Kapanadze S, Eerdekens MH, Kralidis G, Letal J, Sabatschus I, Ahmedzai SH. Cebranopadol, a Novel First-in-Class Analgesic Drug Candidate: First Experience With Cancer-Related Pain for up to 26 Weeks. J Pain Symptom Manage. 2019 Sep;58(3):390-399. doi: 10.1016/j.jpainsymman.2019.05.012. Epub 2019 May 30.