PainPhase 3CORALNCT01964378
CORAL - Cebranopadol Versus Morphine Prolonged-release in Patients With Chronic Moderate to Severe Pain Related to Cancer
A Phase 3 study testing Cebranopadol and Morphine Prolonged Release in people with Pain and Neoplasms, run by Tris Pharma, Inc. at 42 sites in 14 countries.
Trial summary
Pain is one of the most common symptoms associated with malignant tumor. The purpose of this trial is to determine whether cebranopadol is as effective in patients with cancer related pain as morphine sulfate prolonged release (PR). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Neoplasms, Chronic Pain
- What is being tested?
- Cebranopadol and Morphine Prolonged Release
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 42 sitesin 14 countries
- Study dates
- 29 Oct 2013to 16 Oct 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent.
- Negative pregnancy test before first dose.
- Female and male participants willing to use acceptable and highly effective methods of birth control.
- The following criteria must be fulfilled by participants:
- Require daily analgesia for their pain,
- Diagnosed with active cancer,
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- Receiving daily opioid treatment at doses not higher than 90 mg oral morphine or its equivalent (World Health Organization Step II and Step III analgesics) for an appropriate length of time,
- Participants must be dissatisfied with their current pain treatment,
- Participants must be suffering from cancer-related but not cancer therapy-related chronic pain for a period of 4 weeks or more prior to enrollment.
- Eastern Cooperation Oncology Group (ECOG) score 2 or below.
- Average pain intensity over the last 24 hours of 5 or more calculated from the pain assessments recorded during the last 3 days prior to randomization.
- Compliance with the use of the electronic diary defined as at least 3 out of 4 of the 24 hour Numerical Rating Scale entries available during the last 4 days prior to and including the day of allocation to treatment.
Who cannot join
- Evidence of ongoing alcohol and or drug abuse and/or a history of alcohol and/or drug abuse within the last 2 years.
- A clinically significant disease other than cancer which in the investigator's opinion may affect efficacy or safety assessments e.g., significant unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, infectious disease, psychiatric (resulting in disorientation, memory impairment or inability to report accurately) or metabolic disorders.
- Any gastrointestinal disorder that could affect the absorption and/or elimination of Investigational Medicinal Product.
- Any planned major surgery during the trial.
- Known to or suspected of not being able to comply with the trial protocol and the use of Investigational Medicinal Product.
- History of seizure disorder and/or epilepsy or any condition associated with a significant risk of seizure or epilepsy.
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- Known history and/or presence of cerebral tumor or cerebral metastases.
- Moderate to severe hepatic impairment corresponding to Child-Pugh classification B and C. Impaired hepatic cellular integrity indicated by aspartate transaminase or alanine transaminase greater than 3 times the upper limit of normal at the Enrollment Visit.
- Inadequate baseline bone marrow reserve with a white blood cell count below 2000/µL, a platelet count 100 000/µL or less, and a hemoglobin level below 8 g/dL at the Enrollment Visit.
- Impaired renal function. Creatinine clearance less than 60 mL per minute(as per amendment 45 mL per minute) at the Enrollment Visit (calculated from the Cockcroft-Gault formula).
- Forbidden concomitant medications
- Uncontrolled hypertension
- Clinically relevant history of hypersensitivity, allergy or contraindications to opioid medication or any of the excipients of morphine sulfate (Prolonged Released or Immediate Release), or cebranopadol film-coated tablets.
- Chronic hepatitis B or C, or human immunodeficiency virus (HIV) known by history, or presence of active hepatitis B or C within the 3 months before the Enrollment Visit.
- History of torsade de pointes and/or presence of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, or bradycardia).
- Marked prolongation of corrected QT interval (Fridericia) (greater than 450 milliseconds) at the Enrollment Visit.
- Employees of the sponsor, investigator, or trial site or family members of the employees, sponsor, or investigator.
- Concurrent participation in another trial 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.
- Previous participation in this or other trials with cebranopadol with the following exceptions:
- Participants who failed enrollment in this trial only because of exclusion criterion 10, and who may now be eligible can be re-enrolled.
- Participants who failed enrollment due to technical failure of equipment (e.g., ECG machine and e-diary device).
- Participant has received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment.
- Currently not receiving opioid treatment for cancer-related pain at the enrollment visit (i.e., opioid naïve).
Trial locations and contacts
42 sites in 14 countries.
42 sites in 14 countries
Poland8 sites
PL012
Będzin, 42 - 500
PL008
Bydgoszcz, 85-796
PL013
Chorzów, 41-506
PL014
Dąbrowa Górnicza, 41-300
PL003
Gdansk, 80-208
PL010
Gliwice, 44-100
PL015
Warsaw, 01-231
PL002
Włocławek, 87-800
Bulgaria7 sites
BG001
Shumen, 9700
BG008
Sofia, 1330
BG003
Sofia, 1407
BG006
Sofia, 1756
BG007
Sofia, 1784
BG004
Varna, 9003
BG005
Vratsa, 3000
Romania4 sites
RO001
Brasov, 500019
RO002
Cluj-Napoca, 400015
RO009
Constanța, 900591
RO011
Craiova, 200347
Serbia4 sites
RS001
Belgrade, 11000
RS003
Belgrade, 11000
RS002
Kamenitz, 21204
RS005
Zrenjanin, 23000
Slovakia4 sites
SK007
Bratislava, 81107
SK004
Bratislava, 851 07
SK001
Prešov, 080 01
SK005
Pruské, 018 52
Belgium3 sites
BE005
Brussels, 1020
BE002
Ottignies, 1340
BE001
Sint-Niklaas, 9100
About this study
Official title: Efficacy, Safety, and Tolerability of Oral Cebranopadol Versus Morphine Sulfate PR in Subjects With Chronic Moderate to Severe Pain Related to Cancer.
Pain is one of the most common symptoms associated with malignant tumor. The purpose of this trial is to determine whether cebranopadol is as effective in patients with cancer related pain as morphine sulfate prolonged release (PR).
Read the detailed description
The trial comprises an enrollment period, a treatment period (titration and maintenance), and a follow-up period. Participants will receive either cebranopadol or morphine PR for 44 days. Initially participants will be titrated after 2 and then every 4 days to a morphine PR or cebranopadol dose that provides adequate analgesia and is tolerated. The titration period is planned to last 16 days. Thereafter the dose of morphine PR or cebranopadol is to be kept stable for a further 28 days, i.e. no dose adjustments will be allowed during the maintenance period. This 28 day period is the maintenance period. The follow-up period is planned for up to 18 days after the end of last pain medication treatment intake.
- Conditions
- Pain, Neoplasms, Chronic Pain
- Being tested
- Cebranopadol, Morphine Prolonged Release
- Keywords
- cancer pain, neuropathic related cancer pain, morphine, cebranopadol (GRT6005), Numerical Rating Scale
- Medical subject headings
- Pain, Neoplasms, Chronic Pain, Cancer Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CebranopadolDrug
Also called GRT6005
Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
Morphine Prolonged ReleaseDrug
Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
| Study group | Role | What they receive |
|---|---|---|
| Cebranopadol | Experimental | Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day. Receives: Drug: Cebranopadol |
| Morphine Prolonged Release | Active comparator | Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day. Receives: Drug: Morphine Prolonged Release |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Amount of Daily Rescue Medication at the End of the Maintenance Period (Per Protocol Set)
Morphine sulfate immediate release (IR) 10 mg tablets were supplied as rescue medication to trial participants. No dose adjustments of the morphine prolonged release or cebranopadol were allowed during the maintenance period. The daily use of morphine sulfate 10 mg IR tablets was documented by each participant in the trial. The total daily amount of morphine IR was subject to an upper limit recommendation. The primary endpoint is the average amount of daily rescue medication intake over the last 2 weeks of the maintenance period.
Measured: The last 2 weeks of the expected 6-week treatment period.
Average Amount of Daily Rescue Medication at the End of the Maintenance Period (Full Analysis Set)
Morphine sulfate IR 10 mg tablets were supplied as rescue medication to trial participants. No dose adjustments of the morphine prolonged release or cebranopadol were allowed during the maintenance period. The daily use of morphine sulfate 10 mg IR tablets was documented by each participant in the trial. The total daily amount of morphine IR was subject to an upper limit recommendation. The primary endpoint is the average amount of daily rescue medication intake over the last 2 weeks of the maintenance period.
Measured: The last 2 weeks of the expected 6-week treatment period.
Secondary outcomes (1)
Proportion of Participants With Clinically Relevant Pain Reduction at the End of the Maintenance Period
Each participant indicated the level of pain 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 participants entered their pain intensity in their diary on a daily basis. The pain intensity score in the 2 weeks prior to the final evaluation in the maintenance period was compared with the baseline, the baseline pain intensity was calculated based on the 3 days prior to treatment allocation.
The definition of a clinically relevant pain reduction (yes/no) was the presence of at least 1 of the 3 following conditions:
- Average pain intensity (i.e., average of the 24-hour pain intensities over the last 2 weeks of the Maintenance Phase) of less than 4 points on the 11-point NRS, or
- Reduction in average pain intensity by at least 30% (compared to the baseline assessment), or
- Reduction in average pain intensity by at least 2 points (compared to the baseline assessment).
Measured: The last 2 weeks of the expected 6-week treatment period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2013 (estimated)
- Study start29 Oct 2013
- Primary completion16 Oct 2015
- Study completion16 Oct 2015
Why it stopped: low accrual made the study no longer feasible/decision not related to safety and efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tris Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Director Clinical Trials, Study director, Grünenthal GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01964378
- Sponsor's protocol ID
- KF6005/07
- Other IDs
- 2012-001316-35, U1111-1143-1808
- Acronym
- CORAL
- Status last verified
- Jul 2021
- First submitted
- 7 Oct 2013
- Last updated
- 15 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eerdekens MH, Kapanadze S, Koch ED, Kralidis G, Volkers G, Ahmedzai SH, Meissner W. Cancer-related chronic pain: Investigation of the novel analgesic drug candidate cebranopadol in a randomized, double-blind, noninferiority trial. Eur J Pain. 2019 Mar;23(3):577-588. doi: 10.1002/ejp.1331. Epub 2019 Jan 9.
PubMed 30365202
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety, and Tolerability of Oral Cebranopadol Versus Morphine Sulfate PR in Subjects With Chronic Moderate to Severe Pain Related to Cancer.
- ClinicalTrials.gov ID
- NCT01964378
- Acronym / sponsor ID
- CORAL / KF6005/07
- Conditions
- Pain, Neoplasms, Chronic Pain
- Keywords
- cancer pain, neuropathic related cancer pain, morphine, cebranopadol (GRT6005), Numerical Rating Scale
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low accrual made the study no longer feasible/decision not related to safety and efficacy
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Tris Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Oct 2013 (actual)
- Primary completion
- 16 Oct 2015 (actual)
- Study completion
- 16 Oct 2015 (actual)
- First posted
- 17 Oct 2013 (estimated)
- Results
- Posted 30 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pain is one of the most common symptoms associated with malignant tumor. The purpose of this trial is to determine whether cebranopadol is as effective in patients with cancer related pain as morphine sulfate prolonged release (PR).
Detailed description
The trial comprises an enrollment period, a treatment period (titration and maintenance), and a follow-up period. Participants will receive either cebranopadol or morphine PR for 44 days. Initially participants will be titrated after 2 and then every 4 days to a morphine PR or cebranopadol dose that provides adequate analgesia and is tolerated. The titration period is planned to last 16 days. Thereafter the dose of morphine PR or cebranopadol is to be kept stable for a further 28 days, i.e. no dose adjustments will be allowed during the maintenance period. This 28 day period is the maintenance period. The follow-up period is planned for up to 18 days after the end of last pain medication treatment intake.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cebranopadol | Experimental | Drug: CebranopadolOnce daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day. |
| Morphine Prolonged Release | Active comparator | Drug: Morphine Prolonged ReleaseTwice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Signed informed consent.
- Negative pregnancy test before first dose.
- Female and male participants willing to use acceptable and highly effective methods of birth control.
- The following criteria must be fulfilled by participants:
- Eastern Cooperation Oncology Group (ECOG) score 2 or below.
Key exclusion criteria (23 listed)
- Evidence of ongoing alcohol and or drug abuse and/or a history of alcohol and/or drug abuse within the last 2 years.
- A clinically significant disease other than cancer which in the investigator's opinion may affect efficacy or safety assessments e.g., significant unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, infectious disease, psychiatric (resulting in disorientation, memory impairment or inability to report accurately) or metabolic disorders.
- Any gastrointestinal disorder that could affect the absorption and/or elimination of Investigational Medicinal Product.
- Any planned major surgery during the trial.
- Known to or suspected of not being able to comply with the trial protocol and the use of Investigational Medicinal Product.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CebranopadolAlso: GRT6005Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening. | Drug | Cebranopadol |
| Morphine Prolonged ReleaseParticipant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning. | Drug | Morphine Prolonged Release |
Primary outcome
Average Amount of Daily Rescue Medication at the End of the Maintenance Period (Per Protocol Set)
Time frame: The last 2 weeks of the expected 6-week treatment period.
Morphine sulfate immediate release (IR) 10 mg tablets were supplied as rescue medication to trial participants. No dose adjustments of the morphine prolonged release or cebranopadol were allowed during the maintenance period. The daily use of morphine sulfate 10 mg IR tablets was documented by each participant in the trial. The total daily amount of morphine IR was subject to an upper limit recommendation. The primary endpoint is the average amount of daily rescue medication intake over the last 2 weeks of the maintenance period.
Average Amount of Daily Rescue Medication at the End of the Maintenance Period (Full Analysis Set)
Time frame: The last 2 weeks of the expected 6-week treatment period.
Morphine sulfate IR 10 mg tablets were supplied as rescue medication to trial participants. No dose adjustments of the morphine prolonged release or cebranopadol were allowed during the maintenance period. The daily use of morphine sulfate 10 mg IR tablets was documented by each participant in the trial. The total daily amount of morphine IR was subject to an upper limit recommendation. The primary endpoint is the average amount of daily rescue medication intake over the last 2 weeks of the maintenance period.
1 secondary outcome
Proportion of Participants With Clinically Relevant Pain Reduction at the End of the Maintenance Period
Time frame: The last 2 weeks of the expected 6-week treatment period.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30365202Eerdekens MH, Kapanadze S, Koch ED, Kralidis G, Volkers G, Ahmedzai SH, Meissner W. Cancer-related chronic pain: Investigation of the novel analgesic drug candidate cebranopadol in a randomized, double-blind, noninferiority trial. Eur J Pain. 2019 Mar;23(3):577-588. doi: 10.1002/ejp.1331. Epub 2019 Jan 9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Director Clinical Trials study director
Grünenthal GmbH
42 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cebranopadol and Morphine Prolonged Release in people with Pain and Neoplasms, run by Tris Pharma, Inc. at 42 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in Poland, Bulgaria, Romania, Serbia, Slovakia and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Amount of Daily Rescue Medication at the End of the Maintenance Period (Per Protocol Set) (time frame: The last 2 weeks of the expected 6-week treatment period.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01964378, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.