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Trial record 1 of 1 for:    NCT02031432
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CORAL XT - Open-label Extension Trial of the CORAL Trial (CORAL XT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02031432
Recruitment Status : Completed
First Posted : January 9, 2014
Results First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH

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.

Condition or disease Intervention/treatment Phase
Pain Neoplasms Chronic Pain Drug: Cebranopadol Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 18, 2013
Actual Primary Completion Date : April 2016
Actual Study Completion Date : May 3, 2016

Arm Intervention/treatment
Experimental: Cebranopadol

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
Film-coated tablet; strengths: 200, 400, or 600 µg
Other Name: GRT6005




Primary Outcome Measures :
  1. Number of Participants With Treatment Emergent Adverse Event (TEAEs) [ Time Frame: Up to 28 weeks (26 weeks of cebranopadol treatment and 2 weeks follow up after the last dose) ]
    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.


Secondary Outcome Measures :
  1. Intensity of Treatment Emergent Adverse Events [ Time Frame: Up to 28 weeks (26 weeks of cebranopadol treatment and 2 weeks follow-up after the last dose) ]

    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.


  2. Changes From Baseline in the Average Pain Intensity in the Last Week During the Treatment Period [ Time Frame: Baseline Visit (Day 1) to End of Treatment Visit (up to 26 weeks). ]
    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.


Other Outcome Measures:
  1. Outcome of Treatment Emergent Adverse Events (TEAE) [ Time Frame: Baseline (Day 2) to End of trial (i.e., up to Week 28) ]

    The outcome of a TEAE was classified into 1 of the following 6 categories by the investigator, i.e.

    • Recovered/Resolved.
    • Recovered/Resolved with sequelae.
    • Fatal
    • Recovering/Resolving.
    • Not recovered/Not resolved.
    • Unknown (e.g., because the participant is lost to follow up).

  2. Time to Onset of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline (Day 2) to End of trial (up to Week 28) ]
    The median time, in days, from the start of the open-label cebranopadol treatment to the start day of the treatment emergent adverse event (TEAE).

  3. Duration of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline (Day 2) to End of trial (up to Week 28) ]
    An adverse event is any untoward medical occurrence attributed to cebranopadol. Duration of Adverse Event was calculated as stop date minus start date plus 1 for non-missing and partial dates.

  4. Causal Relationship of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline (Day 2) to End of trial (up to Week 28) ]
    The causality of TEAEs was assessed by the investigator as falling into 1 of the following 7 categories: Conditional/Unclassified, Unassessable/Unclassifiable, Not related, Unlikely, Possible, Probable/likely, or Certain. The numbers of TEAEs per category are presented.

  5. Countermeasures Taken for Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline (Day 2) to End of trial (up to Week 28) ]

    The countermeasure of a Treatment Emergent Adverse Event (TEAE) was classified by the investigator as being a study medication-related countermeasure and based on non-study medication countermeasures.

    Non-study medication related countermeasures were categorized as being one of the following: No countermeasure given; A newly started medication or change in dose or route of application of a concomitant medication due to the AE; Other countermeasures, e.g., physical therapy, surgery.

    Study medication-related countermeasures were categorized as being one of the following: Dose not changed; Dose reduced; Drug interrupted; Trial discontinuation.

    Absolute numbers are per category reported.


  6. Number of Participants With Treatment Emergent Adverse Events (TEAEs) Related to Cebranopadol [ Time Frame: Baseline (Day 2) to End of trial (up to Week 28) ]
    Only participants with TEAEs which were assessed by the investigator as falling into one of the 3 categories of causality (Possible, Probable/likely, or Certain) were summarized. The initial breakdown planned based on intensity, outcome, time to onset, duration, and countermeasures was not performed and is therefore not reported.

  7. Columbia-Suicide Severity Rating Scale (C-SSRS) Scores [ Time Frame: Baseline (Day 1) to End of trial (up to Week 28) ]
    The C-SSRS was administered by a clinician who had been certified to administer the C-SSRS at each visit. Suicidal ideation is classified on a 5-item scale (where 1 = Wish to be dead, 2 = Non-specific active suicidal thoughts, 3 = Active Suicidal Ideation with any methods (not plan) without intent to act, 4 = Active Suicidal Ideation with some intent to act, without specific plan, 5 = Active suicidal ideation with a specific plan and intent). The number of participants with suicidal ideation at baseline is presented below for categories with at least 1 participant.

  8. Mean Scores of Chronic Pain Sleep Inventory (CPSI) and Changes From Baseline [ Time Frame: Baseline (Day 1); End of Treatment (up to Week 26) ]

    The CPSI was completed by the participants. It measures 5 items, all on a 100-mm visual analog scale:

    Participant's assessment of Sleep Problem Index subscores and need for sleep medication (the lower the score the better): (1) Trouble falling asleep (0 = never; 100 = always); (2) Needing sleep medication to help fall asleep (0 = never, 100 = always); (3) Awakened by pain during the night (0 = never, 100 = always); and (4) Awakened by pain in the morning (0 = never, 100 = always). The Sleep Problem Index is the sum of items (1), (3), and (4) with a maximum score of 100 indicating maximum sleep problems.

    Participant's assessment of the Overall Quality of Sleep (the higher the score the better): (5) Overall quality of sleep (0 = very poor, 100 = excellent).


  9. Weekly Means of Daily Average Pain Intensity During the First Month of Treatment [ Time Frame: Baseline (Day 1); Titration Weeks 1 and 2; Maintenance Weeks 1 and 2 ]
    Participants were asked: "Please rate your pain by selecting the one number that best describes your pain on average during the last 24 hours." every day in the morning during the first month of treatment (comprising Titration Weeks 1 and 2 and Maintenance Weeks 1 and 2). They 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". The weekly mean value of the 24-hour average pain intensity was calculated as a mean score of these daily entries of average pain intensity for each week.

  10. Worst Pain Intensity in the Last Week of Treatment (Week 26) [ Time Frame: Baseline (Day 1); End of Treatment (Week 26) ]
    Participants were asked: "Please rate your pain by selecting the one number that best describes your pain at its worst during the last week." at some of the visits during the treatment period. They 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". The mean scores of the worst pain intensity were calculated for all participants. Results for baseline and Week 26 are presented.

  11. Weekly Average Number of Breakthrough Pain Episodes [ Time Frame: Baseline (Day 1); End of Treatment (Week 26) ]
    The number of episodes of breakthrough pain during the past week was planned to be collected. However, for some participants, the intensity of breakthrough pain for the past week has been collected instead of the incidence of breakthrough pain events. Since the values of the intensity of breakthrough pain were much higher (maximum of up to 99) than the frequency of pain events, the mean is skewed and cannot be interpreted. The median for the weekly average number of breakthrough pain episodes is less influenced by these values and is reported below.

  12. Mean Scores of Neuropathic Pain Symptom Inventory (NPSI) [ Time Frame: Baseline (Day 1); Weeks 2, 6, 14, 18; End of Treatment (up to Week 26) ]

    Participants with neuropathic pain (determined by the completion of the DN4 [Douleur Neuropathique] questionnaire at enrollment) rated their symptoms of neuropathic pain using the NPSI. Ten out of 12 questions (Q1-3, 5, 6, 8-12) are answered on an 11-point numerical scale (NRS) ranging from 0 (no symptom present) to 10 (worst imaginable).

    The NPSI Total Score was calculated as the sum of the 10 single items scored on the 11-point NRS divided by 100. The mean score is reported on a scale of 0 (no neuropathic pain components present) to 1 (all neuropathic pain components have the maximum imaginable intensity).


  13. EuroQol-5 Dimension (EQ-5D) Health Status Index Outcome [ Time Frame: Baseline (Day 1); End of Treatment (up to Week 26) ]
    Participants answered 5 questions on the 5 dimensions of the EuroQol-5 Dimension Health Questionnaire: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each question has 3 possible answers reflecting 3 levels of impact on the quality of life. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the 5 EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D Health Status Index score between 0 to 1 (with 1 indicating "full health" and 0 representing "dead"). The higher the values (the closer the value is to 1), the better the health status.

  14. EuroQol-5 Dimension (EQ-5D) Health Questionnaire - Visual Analog Scale (VAS) [ Time Frame: Baseline (Day 1); End of Treatment (up to Week 26) ]
    The EuroQoL-5D Health State Visual Analog Scale (VAS) is a participant-rated scale where a single value is ticked for "Your own health state today" on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.

  15. Patient Global Impression of Change (PGIC) [ Time Frame: Baseline (Day 1); End of Treatment (up to Week 26) ]
    In the PGIC, participants indicates the perceived change over the treatment period compared to their condition prior to the start of treatment. Participants are requested to choose 1 of 7 categories. Scores range from "very much improved" to "very much worse". The frequency of responses per category are provided.

  16. Clinical Global Impression of Change (CGIC) [ Time Frame: Baseline (Day 1); End of Treatment Visit (up to Week 26) ]
    For the CGIC assessment, the clinician indicates the perceived change in the patient's condition over the treatment period as compared to the patient's condition prior to the start of treatment. The clinician is requested to choose 1 of 7 categories. Categories range from "very much improved" to "very much worse".

  17. Use of On-demand Opioid Analgesic Medication [ Time Frame: From Day 3 to End of Treatment (up to Week 26) (13 time points) ]
    Participants reported the opioid type and amount of an opioid in mg/day used to relieve their breakthrough pain over the time period in the study. The average number of units of on-demand opioid medication administered during the previous day (reported on Day 3) and during the last 3 days (reported at all other visits) were documented. The number of units of on-demand opioid medication administered during the Treatment Period is summarized descriptively over the treatment period.

  18. Mean Equipotency Ratio of Morphine Sulfate Prolonged Release Compared to Cebranopadol. [ Time Frame: Baseline (Day 1); End of first month of treatment ]
    For those participants, who received morphine prolonged release in the CORAL trial (KF6005/07, NCT01964378) and were, thus, switched from morphine prolonged release to cebranopadol in the CORAL XT trial, the equianalgesic doses of morphine prolonged release and cebranopadol was identified.

  19. Mean Eastern Cooperative Oncology Group Performance Status (ECOG) Scores [ Time Frame: From Baseline (Day 1) through to End of treatment (up to Week 26) (9 time points) ]

    The investigator scores the ECOG performance status for a participant on a 6-point categorical scale as follows:

    • 0 indicates that a participant is "fully active, able to carry on all pre-disease performance without restriction."
    • 1 indicates that a participant is "restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work."
    • 2 indicates that a participant is "ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours."
    • 3 indicates that a participant is "capable of only limited selfcare, confined to bed or chair more than 50% of waking hours."
    • 4 indicates that a participant is "completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair."
    • 5 indicates that a participant is "dead". Mean ECOG performance status scores are calculated for the number of participants with data available.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02031432


Locations
Show Show 22 study locations
Sponsors and Collaborators
Grünenthal GmbH
Investigators
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Study Director: Director Clinical Trials Grünenthal GmbH

Publications of Results:
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Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT02031432    
Other Study ID Numbers: KF6005/09
2013-001877-26 ( EudraCT Number )
U1111-1144-0778 ( Other Identifier: World Health Organization )
First Posted: January 9, 2014    Key Record Dates
Results First Posted: January 18, 2020
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Grünenthal GmbH:
cancer-related pain
cebranopadol
Additional relevant MeSH terms:
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Chronic Pain
Pain
Neurologic Manifestations
Signs and Symptoms