A randomized withdrawal, active- and placebo-controlled, double-blind, multi-center Phase III trial assessing safety and efficacy of oral CG5503 PR* in subjects with moderate to severe chronic malignant tumor-related pain *PR means Prolonged Release and is the recommended nomenclature for use in EU. ER means Extended Release and is the recommended nomenclature for use in USA. "PR" is synonymous with "ER" and is interchangeable in the protocol.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-001985-34-LV
• Date of registration: 09/10/2007
• Prospective Registration: Yes
• Primary sponsor: & Johnson Pharmaceutical Research & Development, L.L.C.
• Public title: A randomized withdrawal, active- and placebo-controlled, double-blind, multi-center Phase III trial assessing safety and efficacy of oral CG5503 PR* in subjects with moderate to severe chronic malignant tumor-related pain *PR means Prolonged Release and is the recommended nomenclature for use in EU. ER means Extended Release and is the recommended nomenclature for use in USA. "PR" is synonymous with "ER" and is interchangeable in the protocol.
• Scientific title: A randomized withdrawal, active- and placebo-controlled, double-blind, multi-center Phase III trial assessing safety and efficacy of oral CG5503 PR* in subjects with moderate to severe chronic malignant tumor-related pain *PR means Prolonged Release and is the recommended nomenclature for use in EU. ER means Extended Release and is the recommended nomenclature for use in USA. "PR" is synonymous with "ER" and is interchangeable in the protocol.
• Date of first enrolment: 15/02/2008
• Target sample size: 573
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001985-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

France, Latvia

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must have signed an informed consent document
indicating that they understand the purpose of and procedures
required for the trial and are willing to participate in the trial.
• Male and non-pregnant, non-lactating female subjects. Sexually
active women must be post menopausal, surgically sterile, or
practicing an effective method of birth control (e.g. prescription oral
contraceptives, contraceptive injections, intrauterine device, double
barrier method, contraceptive patch, male partner sterilization)
before entry and throughout the trial. Female subjects must have a
negative pregnancy test at Screening.
• At least 18 years of age.
• Chronic malignant tumor-related pain.
• Subjects who are opioid-naïve or pretreated with an equianalgesic
dose range equivalent of up to 160 mg oral morphine per day and are dissatisfied with prior treatment.
• Subjects with a mean pain intensity = 5 points (11-point NRS) on
the day of randomization at the start of Titration phase.
• Expected course of the disease and the pain that will permit
compliance with the trial protocol over the entire trial period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
History of alcohol and/or drug abuse in the investigator’s judgment,
based on patient history and physical examination.
• The subject has 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, psychiatric (resulting in
disorientation, memory impairment or inability to report accurately)
or metabolic disturbances.
• Any scheduled surgery during the trial.
• Any painful procedure during the trial that may, in the opinion of
the Investigator, affect the efficacy or safety assessments.
• Employees of the investigator or trial center, with direct
involvement in the proposed trial or other trials under the direction
of that investigator or trial center, as well as family members of the
employees or the investigator.
• Known to or suspected of not being able to comply with the
protocol and the use of CG5503 or morphine.
• Have received an experimental drug or used an experimental
medical device within 30 days before the planned start of treatment.
• Participation in another trial concurrently.
• Subjects who have participated in previous trials of CG5503.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

The treatment of chronic tumor-related pain.
MedDRA version: 9.1 Level: LLT Classification code 10033371 Term: Pain
MedDRA version: 9.1 Level: PT Classification code 10033371 Term: Pain

Intervention(s)

Product Name: CG5503, R331333, BN200
Product Code: CG5503, R331333, BN200
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Other descriptive name: (-)-(1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: CG5503, R331333, BN200
Product Code: CG5503, R331333, BN200
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Other descriptive name: (-)-(1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: CG5503, R331333, BN200
Product Code: CG5503, R331333, BN200
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Other descriptive name: (-)-(1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: CG5503, R331333, BN200
Product Code: CG5503, R331333, BN200
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Other descriptive name: (-)-(1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: CG5503, R331333, BN200
Product Code: CG5503, R331333, BN200
Pharmaceutical Form: Prolonged

Primary Outcome(s)

Main Objective: The primary objective of this trial is to evaluate the safety and efficacy orally administered CG5503 PR tablets BID over 4 weeks (Maintenance phase) in subjects with moderate to severe chronic malignant tumor-related pain in comparison with placebo.

Primary end point(s): The primary efficacy endpoint is the proportion of subjects classified as responders at the end of the 4-week Maintenance phase.
Responders are subjects who meet all of the following criteria:
• Complete 28 days of the Maintenance phase.
• Have a mean pain intensity < 5.0 point on an 11-point NRS during the Maintenance phase (the twice daily current pain score averaged over Days 18 to 43).
• Do not use more than 2.0 doses of rescue medication/day on average during the Maintenance phase (Days 18 to 43).

Secondary Objective: • To compare efficacy and safety of CG5503 PR with morphine sulfate CR during the Titration phase as well as over the whole treatment phase.
• To collect pharmacokinetic information for dose verification and population pharmacokinetic analyses.

Secondary ID(s)

KF5503/16/ R331333-PAI-3014