CORAL - Cebranopadol Versus Morphine Prolonged-release in Patients With Chronic Moderate to Severe Pain Related to Cancer

NCT ID: NCT01964378

Last Updated: 2021-07-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-29
• Study Completion Date: 2015-10-16

Brief 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).

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cebranopadol

Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.

Group Type: EXPERIMENTAL

Cebranopadol

Intervention Type: DRUG

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 Release

Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.

Group Type: ACTIVE_COMPARATOR

Morphine Prolonged Release

Intervention Type: DRUG

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.

Interventions

Cebranopadol

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.

Intervention Type: DRUG

Morphine Prolonged Release

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.

Intervention Type: DRUG

Other Intervention Names

GRT6005

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent.

2. Negative pregnancy test before first dose.

3. Female and male participants willing to use acceptable and highly effective methods of birth control.

4. The following criteria must be fulfilled by participants:

1. Require daily analgesia for their pain,

2. Diagnosed with active cancer,

3. 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,

4. Participants must be dissatisfied with their current pain treatment,

5. 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.

5. Eastern Cooperation Oncology Group (ECOG) score 2 or below.

6. 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.

7. 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.

Exclusion Criteria

1. Evidence of ongoing alcohol and or drug abuse and/or a history of alcohol and/or drug abuse within the last 2 years.

2. 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.

3. Any gastrointestinal disorder that could affect the absorption and/or elimination of Investigational Medicinal Product.

4. Any planned major surgery during the trial.

5. Known to or suspected of not being able to comply with the trial protocol and the use of Investigational Medicinal Product.

6. History of seizure disorder and/or epilepsy or any condition associated with a significant risk of seizure or epilepsy.

7. Known history and/or presence of cerebral tumor or cerebral metastases.

8. 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.

9. 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.

10. 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).

11. Forbidden concomitant medications

12. Uncontrolled hypertension

13. 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.

14. 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.

15. History of torsade de pointes and/or presence of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, or bradycardia).

16. Marked prolongation of corrected QT interval (Fridericia) (greater than 450 milliseconds) at the Enrollment Visit.

17. Employees of the sponsor, investigator, or trial site or family members of the employees, sponsor, or investigator.

18. 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.

19. 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).

20. Participant has received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment.

21. Currently not receiving opioid treatment for cancer-related pain at the enrollment visit (i.e., opioid naïve).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tris Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Director Clinical Trials

Role: STUDY_DIRECTOR

Grünenthal GmbH

Locations

AT004

Vienna, , Austria

BE005

Brussels, , Belgium

BE002

Ottignies, , Belgium

BE001

Sint-Niklaas, , Belgium

BG001

Shumen, , Bulgaria

BG008

Sofia, , Bulgaria

BG003

Sofia, , Bulgaria

BG006

Sofia, , Bulgaria

BG007

Sofia, , Bulgaria

BG004

Varna, , Bulgaria

BG005

Vratsa, , Bulgaria

CL005

Temuco, , Chile

HR001

Zagreb, , Croatia

DK006

Aalborg, , Denmark

DK004

Herlev, , Denmark

DE008

Böhlen, , Germany

DE010

München, , Germany

HU004

Gyula, , Hungary

HU002

Miskolc, , Hungary

HU011

Nyíregyháza, , Hungary

PL012

Będzin, , Poland

PL008

Bydgoszcz, , Poland

PL013

Chorzów, , Poland

PL014

Dąbrowa Górnicza, , Poland

PL003

Gdansk, , Poland

PL010

Gliwice, , Poland

PL015

Warsaw, , Poland

PL002

Włocławek, , Poland

RO001

Brasov, , Romania

RO002

Cluj-Napoca, , Romania

RO009

Constanța, , Romania

RO011

Craiova, , Romania

RS001

Belgrade, , Serbia

RS003

Belgrade, , Serbia

RS002

Kamenitz, , Serbia

RS005

Zrenjanin, , Serbia

SK007

Bratislava, , Slovakia

SK004

Bratislava, , Slovakia

SK001

Prešov, , Slovakia

SK005

Pruské, , Slovakia

ES012

Barcelona, , Spain

UK004

Leeds, , United Kingdom

Countries

Austria; Belgium; Bulgaria; Chile; Croatia; Denmark; Germany; Hungary; Poland; Romania; Serbia; Slovakia; Spain; United Kingdom

References

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.

Reference Type: RESULT

PMID: 30365202 (View on PubMed)

Other Identifiers

2012-001316-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1143-1808

Identifier Type: OTHER

Identifier Source: secondary_id

KF6005/07

Identifier Type: -

Identifier Source: org_study_id