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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT02031432
First received: December 12, 2013
Last updated: May 10, 2016
Last verified: May 2016
  Purpose
The purpose of this trial is 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 will be collected how cebranopadol affects pain and well-being in patients suffering from cancer-related pain.

Condition Intervention Phase
Pain Neoplasms Chronic Pain Drug: Cebranopadol Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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.

Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • Absolute and relative frequencies of Treatment Emergent Adverse Event (TEAEs) [ Time Frame: Day 2; end of week 28 ]
    Any adverse event that occurs after the first intake of cebranopadol.


Secondary Outcome Measures:
  • Absolute and relative frequencies of Treatment Emergent Adverse Events (TEAEs) by clinical intensity [ Time Frame: Day 2; end of week 28 ]

    A Treatment Emergent Adverse Event (TEAE) is defined as any Adverse Event (AE) that occurred on or after the first intake of cebranopadol. TEAEs will be 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 changes over time, the maximum intensity observed during the whole duration of the AE will be documented.


  • Average pain intensity (11-point NRS) in the last week [ Time Frame: Day 1; end of week 26 ]
    Participants will be asked: "Please rate your pain by selecting the one number that best describes your pain on average during the last week." at some of the visits . They will score 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 scores will be calculated as mean values for all patients for each assessment time point.


Other Outcome Measures:
  • The absolute and relative frequencies of Treatment Emergent Adverse Events (TEAE) by outcome [ Time Frame: Day 2; end of week 28 ]

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

    1. Recovered/Resolved.
    2. Recovered/Resolved with sequelae.
    3. Fatal
    4. Recovering/Resolving.
    5. Not recovered/Not resolved.
    6. Unknown (e.g., because the participant is lost to follow-up ).

    The relative frequencies for each of the outcome categories will be based on the total number of adverse events.


  • Time to onset of Treatment Emergent Adverse Events [ Time Frame: Day 2; end of week 28 ]
    The time, in days, from the start of the open-label cebranopadol treatment to the start day of the treatment emergent adverse event (TEAE) and reported by system organ class (SOC).

  • Duration of Treatment Emergent Adverse Events [ Time Frame: Day 2; end of week 28 ]
    An Adverse Event is any untoward medical occurrence attributed to cebranopadol. Duration of Adverse Event will be calculated as stop date minus start date plus 1 for non-missing and partial dates based on System Organ Class definitions.

  • The absolute and relative frequencies of Treatment Emergent Adverse Events (TEAEs) by causal relationship [ Time Frame: Day 2; end of week 28 ]

    The causality of a Treatment Emergent Adverse Events (TEAEs) will be assessed by the trial doctor as falling into one of the following 7 categories:

    1. Conditional/Unclassified
    2. Unassessable/Unclassifiable
    3. Not related
    4. Unlikely
    5. Possible
    6. Probable/likely
    7. Certain.

    The relative frequencies for each of the relationship categories will be based on the total number of adverse events.


  • The absolute and relative frequencies of Treatment Emergent Adverse Events (TEAEs) by countermeasure [ Time Frame: Day 2; end of week 28 ]

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

    Study medication related countermeasures will be categorized as being one of the following:

    1. Dose not changed.
    2. Dose reduced.
    3. Drug interrupted.
    4. Trial discontinuation.

    Non-study medication related countermeasures will be categorized as being one of the following:

    1. No countermeasure given.
    2. A newly started medication or change in dose or route of application of a concomitant medication due to the AE.
    3. Other countermeasures, e.g., physical therapy, surgery.

    The relative frequencies for each of the outcome categories will be based on the total number of adverse events.


  • Incidence, Intensity, Outcomes, Time to onset, Duration and countermeasures of Treatment Emergent Adverse Events considered to be at least possibly related to cebranopadol [ Time Frame: Day 2; end of week 28 ]
    Only those Treatment Emergent Adverse Events (TEAEs) which were assessed by the trial doctor as following into one of the 3 categories of causality: Possible, Probable/likely, or Certain, will be summarized. Absolute and relative frequencies will be calculated for 3 parameters (intensity, outcomes and countermeasures). Time to onset and duration will be summarized as calculated means.

  • Columbia-Suicide Severity Rating Scale (C-SSRS) Scores [ Time Frame: Day 1; end of week 28 ]
    The C-SSRS will be administered by a clinician who has been certified to administer the C-SSRS at each patient visit. The severity of both suicidal ideation and suicidal behavior will be reported and calculated as mean scores.

  • The mean scores of Chronic Pain Sleep Inventory [ Time Frame: Day 1; end of week 26 ]

    The Chronic Sleep Inventory (CPSI) measures 5 items:

    • trouble falling asleep,
    • needing sleep medication,
    • awakened by pain during the night
    • awakened by pain in the morning
    • overall quality of sleep on a 100 mm visual analog scale. The CPSI will be completed by participants.

  • Weekly means of daily average pain intensity [ Time Frame: Day 1; end of first month ]
    Participants will be 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 the treatment. They will score 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 h average pain intensity will be calculated as a mean score of these daily entries of average pain intensity for each week.

  • Worst pain intensity in the last week [ Time Frame: Day 1; end of week 26 ]
    Participants will be 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 . They will score 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 scores will be calculated as mean values for all participants for each assessment time point.

  • Incidence of breakthrough pain [ Time Frame: Day 1; end of week 26 ]
    Participants will report the number of episodes of breakthrough pain over the open label period. The average number of the breakthrough pain episodes over all participants will be calculated.

  • Mean scores of neuropathic pain symptom inventory [ Time Frame: Day 1; end of week 26 ]
    The participant with neuropathic pain (determined by the completion of the DN4 [Douleur Neuropathique] at enrollment) will rate their symptoms of neuropathic pain on Neuropathic Pain Symptom Inventory (NPSI). Ten out of 12 questions are answered on an 11-point scale 0 (no symptom present) to 10 (worst imaginable). Two out of 12 questions are answered by selecting one of 5 possible responses. Mean scores of NPSI will be calculated.

  • EuroQol-5 Dimension (EQ-5D) Health Questionnaire over time [ Time Frame: Day 1; end of week 26 ]

    The EuroQol-5 Dimension Health Questionnaire is a generic health related quality of life instrument. The participants will answer 5 questions on 5 dimensions of their health related quality of life: 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.

    Participants will also rate their current health state on the visual analogue scale (VAS; 0 = worst imaginable health state and 100 = best imaginable health state). A positive change indicates an improvement.


  • Patient global impression of change (PGIC) [ Time Frame: Day 1; end of week 26 ]
    In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period compared to his condition prior to the start of treatment. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.

  • Use of on demand opioid analgesic medication [ Time Frame: Day 2; end of week 26 ]
    Participants will report the opioid and amount of an opioid in mg/day used to relieve their breakthrough pain over the time period in the trial.

  • Mean Equipotency Ratio of Morphine sulfate Prolonged Release compared to cebranopadol. [ Time Frame: Day 1; end of first month ]
    For those participants, who received morphine prolonged release in the CORAL trial and were, thus, switched from morphine prolonged release to cebranopadol in the CORAL XT trial, the equianalgesic doses of morphine prolonged release and cebranopadol will be identified.

  • Mean Eastern Cooperative Oncology Group Performance Status (ECOG) Scores [ Time Frame: Day 1 through end of week 26 ]

    The trial doctor scores the Eastern Cooperative Oncology Group Performance Status (ECOG). A participant is scored 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".

  • Clinical Global Impression of Change (CGIC) [ Time Frame: Day 1; end of Week 26 ]
    In the Clinical Global Impression of Change (CGIC) the clinician indicates the perceived change in patient's condition over the treatment period as compared to patient's condition prior to the start of treatment. The clinician is requested to choose one of seven categories. Scores range from very much improved to very much worse.


Enrollment: 76
Study Start Date: December 2013
Study Completion Date: May 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cebranopadol Drug: Cebranopadol
Cebranopadol 200 µg to 1000 µg per day taken once a day in the morning.

Detailed Description:
The trial consists of 3 phases: Titration Phase, Maintenance Phase, and Follow-Up. The total duration of the trial will be approximately 28 weeks for each individual participant, including the Follow-up. The participants will receive cebranopadol for a maximum of approximately 26 weeks.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02031432

Locations
Austria
AT004
Vienna, Austria, 1090
Belgium
BE001
Sint-Niklaas, Belgium, 9100
Bulgaria
BG001
Shumen, Bulgaria, 9700
BG008
Sofia, Bulgaria, 1330
BG003
Sofia, Bulgaria, 1407
BG004
Sofia, Bulgaria, 1407
Denmark
DK006
Aalborg, Denmark, 9000
DK004
Herlev, Denmark, 2730
Germany
DE008
Böhlen, Germany, 4564
DE010
Munich, Germany, 81377
Hungary
HU011
Nyiregyhaza, Hungary, 4400
Poland
PL012
Będzin, Poland, 42-500
PL014
Dąbrowa Górnicza, Poland, 41-300
PL003
Gdansk, Poland, 80-208
PL010
Gliwice, Poland, 44-100
Romania
RO002
Cluj-Napoca, Romania, 400015
Serbia
RS003
Belgrade, Serbia, 11000
RS002
Sremska Kamenica, Serbia, 21204
RS005
Zrenjanin, Serbia, 23000
Slovakia
SK004
Bratislava, Slovakia, 851 07
SK001
Presov, Slovakia, 08001
SK005
Pruské, Slovakia, 018 52
Sponsors and Collaborators
Grünenthal GmbH
Investigators
Study Director: Director Clinical Trials Grünenthal GmbH
  More Information

Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT02031432     History of Changes
Other Study ID Numbers: KF6005/09
2013-001877-26 ( EudraCT Number )
U1111-1144-0778 ( Other Identifier: World Health Organization )
Study First Received: December 12, 2013
Last Updated: May 10, 2016

Keywords provided by Grünenthal GmbH:
cancer-related pain
cebranopadol

Additional relevant MeSH terms:
Chronic Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on June 27, 2017