CORAL XT - Open-label Extension Trial of the CORAL Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Pain, Neoplasms, Chronic Pain

Intervention / Treatment
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* Drug: Cebranopadol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cebranopadol<br>Cebranopadol 200 µg to 1000 µg per taken taken once a day in the morning. Allowed dose levels in the Maintenance Phase were 200, 400, 600, 800, or 1000 µg per day. | Drug: Cebranopadol<br>* Film-coated tablet; strengths: 200, 400, or 600 µg<br>* Other names: GRT6005;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Event (TEAEs) | The safety of cebranopadol was assessed by the number of participants with treatment emergent adverse events (TEAEs). A TEAE was any adverse event that occurred after the first administration of investigational medicinal product (IMP), i.e., cebranopadol in this study. In addition, pretreatment adverse events which worsened during the treatment period were also considered TEAEs. | Up to 28 weeks (26 weeks of cebranopadol treatment and 2 weeks follow up after the last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of Treatment Emergent Adverse Events | A Treatment Emergent Adverse Event (TEAE) was defined as any Adverse Event (AE) that occurred on or after the first intake of cebranopadol or a pretreatment AE which worsened during the treatment period. TEAEs were classified by the investigator as falling into 1 of 3 categories: Mild: Signs and symptoms that can be easily tolerated. Symptoms can be ignored and disappear when the participant is distracted. Moderate: Symptoms cause discomfort but are tolerable; they cannot be ignored and affect concentration. Severe: Symptoms which affect usual daily activity. For TEAE where the intensity changed over time, the maximum intensity observed during the whole duration of the adverse event was documented. | Up to 28 weeks (26 weeks of cebranopadol treatment and 2 weeks follow-up after the last dose) | 
| Changes From Baseline in the Average Pain Intensity in the Last Week During the Treatment Period | Participants were asked Please rate your pain by selecting the one number that best describes your pain on average during the last week. and scored their average pain intensity during the last week of the treatment period 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. The absolute change from baseline for the average pain intensity during the last week was determined for all participants that scored their pain intensities. A mean value for all participants was calculated. | Baseline Visit (Day 1) to End of Treatment Visit (up to 26 weeks). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer-related pain, cebranopadol