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

NCT01964378 | Terminated Phase 3 Results DMC

• 3 other identifiers: KF6005/072012-001316-35U1111-1143-1808
• Study Type: interventional
• Target: 200
• Locations: 14 countries
• Sites: 42

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).

Conditions

Pain; Neoplasms; Chronic Pain

Keywords

cancer pain; neuropathic related cancer pain; morphine; cebranopadol (GRT6005); Numerical Rating Scale

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  The last 2 weeks of the expected 6-week treatment period.

Other Outcomes (11)

• Change in Weekly Mean of the Daily Average Pain Intensity Score From Baseline

  Baseline; last 2 weeks of the expected 6-week treatment period

• Response Rate to Treatment

  Baseline; last 2 weeks of the expected 6-week treatment period

• Overall Score of the Neuropathic Pain Symptom Inventory (NPSI)

  Baseline; End-of-Treatment Visit (Week 6)

Study Arms (2)

Cebranopadol

EXPERIMENTAL

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

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.

Drug: Morphine Prolonged Release

Interventions

Cebranopadol 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.

Also known as: GRT6005

Cebranopadol

Morphine Prolonged Release 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.

Morphine Prolonged Release

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Tris Pharma, Inc.: lead

Study Sites (42)

AT004

Vienna, 1090, Austria

Location

BE005

Brussels, 1020, Belgium

Location

BE002

Ottignies, 1340, Belgium

Location

BE001

Sint-Niklaas, 9100, Belgium

Location

BG001

Shumen, 9700, Bulgaria

Location

BG008

Sofia, 1330, Bulgaria

Location

BG003

Sofia, 1407, Bulgaria

Location

BG006

Sofia, 1756, Bulgaria

Location

BG007

Sofia, 1784, Bulgaria

Location

BG004

Varna, 9003, Bulgaria

Location

BG005

Vratsa, 3000, Bulgaria

Location

CL005

Temuco, 4810469, Chile

Location

HR001

Zagreb, 10000, Croatia

Location

DK006

Aalborg, 9000, Denmark

Location

DK004

Herlev, 2730, Denmark

Location

DE008

Böhlen, 4564, Germany

Location

DE010

München, 81377, Germany

Location

HU004

Gyula, 5700, Hungary

Location

HU002

Miskolc, 3526, Hungary

Location

HU011

Nyíregyháza, 4400, Hungary

Location

PL012

Będzin, 42 - 500, Poland

Location

PL008

Bydgoszcz, 85-796, Poland

Location

PL013

Chorzów, 41-506, Poland

Location

PL014

Dąbrowa Górnicza, 41-300, Poland

Location

PL003

Gdansk, 80-208, Poland

Location

PL010

Gliwice, 44-100, Poland

Location

PL015

Warsaw, 01-231, Poland

Location

PL002

Włocławek, 87-800, Poland

Location

RO001

Brasov, 500019, Romania

Location

RO002

Cluj-Napoca, 400015, Romania

Location

RO009

Constanța, 900591, Romania

Location

RO011

Craiova, 200347, Romania

Location

RS001

Belgrade, 11000, Serbia

Location

RS003

Belgrade, 11000, Serbia

Location

RS002

Kamenitz, 21204, Serbia

Location

RS005

Zrenjanin, 23000, Serbia

Location

SK007

Bratislava, 81107, Slovakia

Location

SK004

Bratislava, 851 07, Slovakia

Location

SK001

Prešov, 080 01, Slovakia

Location

SK005

Pruské, 018 52, Slovakia

Location

ES012

Barcelona, 8022, Spain

Location

UK004

Leeds, LS14 6UH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30365202 RESULT

MeSH Terms

Conditions

Pain; Neoplasms; Chronic Pain; Cancer Pain

Interventions

6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenylspiro(cyclohexane-1,1'(3'H)-pyrano(3,4-b)indol)-4-amine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

As the enrollment was stopped for business reasons, only a fraction of the planned number of participants was enrolled; however, the trial still has a larger participant number per treatment than a majority of trials in cancer pain so far.

Results Point of Contact

• Title: Study Director
• Organization: Grünenthal GmbH

Clinical-Trials@grunenthal.com

+49 241 569 3223

Study Officials

• Director Clinical Trials

  Grünenthal GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2013
• First Posted: October 17, 2013
• Study Start: October 29, 2013
• Primary Completion: October 16, 2015
• Study Completion: October 16, 2015
• Last Updated: July 15, 2021
• Results First Posted: December 30, 2019

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1); AU (1); SE (4); SL (4); GB (1); CL (1); ES (1); DK (2); RO (4); HU (3); PL (8); DE (2); BU (7); BE (3)