The primary objective of this trial is to describe the safety and tolerability of prolonged exposure to cebranopadol in subjects suffering from cancer related pain
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Pijn bij kanker
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for this trial is the incidence of treatment emergent
adverse events (TEAEs).
Secondary outcome
The secondary safety endpoint for this trial is the intensity of TEAEs.
The secondary efficacy endpoint for this trial is the average pain intensity
(11-point numerical rating scale [NRS]) in the last week during the Treatment
Period and changes from baseline
Background summary
Cebranopadol is a highly potent mixed NOP/opioid receptor agonist, currently
under development for the indication of severe chronic nociceptive pain
requiring opioid analgesia.
To fulfill the European Medicines Agency (EMA) requirements for this
indication, a Phase III trial is planned in subjects with chronic moderate to
severe pain related to cancer (KF6005/07). The main objective of KF6005/07 is
to demonstrate the non-inferior efficacy of cebranopadol compared
to morphine sulfate PR.
Given that cebranopadol is intended for chronic use, safety and tolerability
data will need to be collected in the targeted population during prolonged
exposure to cebranopadol (ICH E1 guideline).
To meet this requirement, KF6005/09 will include subjects who completed their
treatment with morphine sulfate PR or cebranopadol in KF6005/07. These subjects
will be given the opportunity to participate in KF6005/09 and receive treatment
with cebranopadol for up to approximately 26 weeks.
Given the underlying cancer disease, the anticipated poor survival of the
targeted population and the resulting high discontinuation rate, the overall
duration of the trial will be limited to approximately 28 weeks.
Study objective
The primary objective of this trial is to describe the safety and tolerability
of prolonged exposure to cebranopadol in subjects suffering from cancer related
pain
Study design
This is a non-randomized, multi-site, open-label, single-arm Phase III trial to
describe the safety and tolerability of oral cebranopadol for 26-weeks in
subjects with cancer-related pain who have completed treatment in the KF6005/07
trial.
Estimated date of first subject in/last subject out: Q2 2014/ Q3 2016. Subjects
are expected to be in the trial for approximately 28 weeks (approximately 199
days).
Intervention
The IMP will be taken orally twice daily throughout the Titration Phase and
the Maintenance Phase. The IMP intake must be documented in the e-diary during
the treatment period on a daily basis. The different daily doses during the
Titration Phase and the Maintenance Phase will be administered using the
available dose strengths of cebranopadol (200 µg, 400 µg, 600 µg) and morphine
(15 mg, 30 mg, and 45 mg) and the matching placebo tablets or capsules. The
starting dose of cebranopadol will be 200 µg per day. The maximum daily dose of
cebranopadol is 1000 µg. The minimum daily dose of cebranopadol is 200 µg. The
incremental/decremental dose of cebranopadol is 200 µg per day. The aim of the
titration is to reach the subject*s individual optimal dose defined as a
balance between self-reported analgesia and side effects. The investigator will
have access to each subject*s recordings of daily pain ratings and should take
these into account in titration decisions. If the tolerability is considered
acceptable by both the subject and the investigator, and there appears to be
sub-optimal efficacy, i.e., high pain intensity and/or the need to use rescue
medication, the investigator should titrate the subject to a higher dose. If
the tolerability is considered unacceptable by the subject or the investigator,
the investigator should down-titrate the dose. The selected dose at the end of
the Titration phase will be used by the subjects during the Maintenance Phase.
To ensure adequate efficacy assessments, changes in dose during the Maintenance
Phase will be prohibited.
Study burden and risks
During hospital visits blood will be drawn. The insertion of the needle for the
venipuncture will be experienced unpleasant and\or painful by the patient.
There might be hemorrhage at the injection site.
in additon there may be some side effects like nausea, vomiting, fatigue,
dizziness, and somnolence (drowsiness).
Besides these side effects, other effects, known for classical opioids
(narcotics) may occur under treatment with cebranopadol although a causal
relationship is not yet evident. Examples of such opioid-typical effects are
low blood pressure, slower heartbeat, decrease in breathing rate, constipation,
inability to empty the bladder, and drug withdrawal symptoms upon cessation.
All opioid drugs including cebranopadol can cause dependency.
Sometimes people have allergic reactions to drugs that, in severe cases, can
lead to death. Some signs of an allergic reaction are
* Rash, difficulty breathing, wheezing, sudden drop in blood pressure, swelling
around the mouth, throat, or eyes, fast pulse, sweating, itching.
People who have asthma are more likely to have an allergic reaction to the
trial medications than people who don*t have asthma.
Zieglerstrasse 6
Aachen 52099
DE
Zieglerstrasse 6
Aachen 52099
DE
Listed location countries
Age
Inclusion criteria
1. Informed consent signed indicating that the subject understands the purpose of and procedures required for the trial and is willing to participate in the trial.
2. Subjects must be at least 18 years of age at the Enrollment Visit (Visit 1).
3. Women of childbearing potential must have a negative pregnancy test at Visit 1 and must not be lactating at Visit 1.
4. Subjects must be willing to use medically acceptable and highly effective methods of birth control. For women of childbearing potential a medically acceptable and highly effective method of birth control is defined as any form of contraception with a low failure rate defined as <1% per year. For example:
* Hormonal contraceptives for the duration of the trial and until for at least 4 weeks after Final Visit.
* An intra-uterine device.
Additional barrier contraception must be used by the partner for the duration of the trial. A double-barrier method should be supplemented by the use of spermicidal agents. Women of non-childbearing potential may be included if surgically sterile (i.e., after hysterectomy) or post-menopausal for at least 2 years and
<=55 years old.
For men:
Men have to use barrier contraception (condom) during sexual intercourse for the duration of the trial. The male subject has to take care that the female sexual partner uses at least 1 additional method of contraception with a low failure rate defined as <1% per year (e.g., oral contraceptives) during this time frame.
5. Subjects who have completed treatment in KF6005/07 and are still in need of around-the-clock pain analgesia with strong opioids.
Exclusion criteria
1. The subject has a clinically significant disease or condition 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, psychiatric (resulting in disorientation, memory impairment or inability to report accurately) or metabolic disorders or clinically relevant
history of hypersensitivity, allergy or contraindications to opioid medication or any of the excipients of cebranopadol film-coated tablets.
2. Known to or suspected of not being able to comply with the protocol and the use of cebranopadol.
3. Subjects taking forbidden concomitant medications or not being able to follow the rules of use of concomitant treatment
4. History of torsade de pointes and/or presence of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, bradycardia).
5. 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 ( this does not include observational studies), or previous participation in this trial.
6. Employees of the sponsor, investigator, or trial site or family members of the employees, sponsor, or investigator.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001877-26-NL |
| CCMO | NL46489.098.14 |