A Randomized, Double-Blind, Active- and Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Multiple Doses of CG5503 Immediate Release Formulation in the Treatment of Acute Pain From Total Hip Replacement Surgery Followed by a Voluntary Open-Label Extension. - n/a

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-004513-18-EE
• Date of registration: 10/09/2007
• Prospective Registration: Yes
• Primary sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Public title: A Randomized, Double-Blind, Active- and Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Multiple Doses of CG5503 Immediate Release Formulation in the Treatment of Acute Pain From Total Hip Replacement Surgery Followed by a Voluntary Open-Label Extension. - n/a
• Scientific title: A Randomized, Double-Blind, Active- and Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Multiple Doses of CG5503 Immediate Release Formulation in the Treatment of Acute Pain From Total Hip Replacement Surgery Followed by a Voluntary Open-Label Extension. - n/a
• Date of first enrolment: 16/10/2007
• Target sample size: 1100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004513-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic, Estonia, Finland, France, Hungary, Lithuania, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
·Man or woman, between 18 to 85 years of age, inclusive
·Signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
·In countries where pharmacogenomics testing is allowed and sites choose to participate, subjects will sign an informed consent for genetic testing, indicating whether they do or do not wish to participate in the genetic part of the study; participation in the genetic testing component is not mandatory for participation in the study·
·Physical status rated as less than or equal to 3 on the American Society of Anesthesiologist (ASA) rating scale (see Attachment 1)
·Scheduled to undergo standard primary (non-revision) unilateral total hip replacement surgery due to non-inflammatory degenerative joint disease (NIDJD).
·Women must be postmenopausal, surgically sterile, or practicing or agree to practice an effective method of birth control if they are sexually active before entry and throughout the study (effective methods of birth control include prescription hormonal contraceptives, intrauterine devices, double-barrier method, and male partner sterilization). Women of childbearing potential must have a negative serum b human chorionic gonadotropin (b-hCG) pregnancy test at screening and a negative urine pregnancy test before surgery
·Subjects must use satisfactory contraception from first dose up to 7 days after last dose of study drug.
·Baseline pain intensity more than or equal to 4 on an 11-point (0 to 10) Pain Intensity NRS, rated within 30 minutes before randomization
·Qualifying baseline pain intensity measurements occur within 6 hours of the termination of PCA (after a minimum of 12 hours of PCA), during the postoperative surgical period.
·Must be able to complete all study related procedures and requirements throughout the study 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 seizure disorder or epilepsy suggested by the presence of any of the following:–
Mild or moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm within 1 year of screening, or
–Severe traumatic brain injury, episode(s) of unconsciousness or posttraumatic amnesia of more than 24 hours’ duration within 15 years of screening.
·History of malignancy within the past 2 years before the start of the study, with the exception of basal cell carcinoma
·History of alcohol or drug abuse in the investigator’s judgment based on subject history and physical examination
·Evidence of active infections that may spread to other areas of the body (e.g., osteomyelitis, pyogenic infection of the hip, Hepatitis B or C, or other overt infections) or a history human immunodeficiency virus (HIV) 1 or 2.
·Significant concomitant autoimmune inflammatory conditions that could affect efficacy or safety, in the opinion of the investigator
·Acute crystal-induced arthropathy within the previous 6 months before the screening period of the study
·Has laboratory values reflecting severe renal insufficiency indicated by a creatinine clearance less than or equal to 30 mL/min.
·Moderately or severely impaired hepatic function, or subjects with alanine aminotransaminase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN)); or evidence of significant anemia indicated by hemoglobin (Hgb) levels less than or equal to 8 g/dL
·Uncontrolled or poorly controlled post-traumatic stress disorder generalized anxiety disorder (GAD), depression, psychiatric or other significant medical conditions
·Treated with anticonvulsants, monoamine oxidase inhibitors, tricyclic antidepressants, neuroleptics, or serotonin norepinephrine reuptake inhibitor (SNRI) within 2 weeks before screening, (selective serotonin reuptake inhibitor [SSRI] treatments are allowed if taken for at least 30 days before the screening period of the study at an unchanged dose)
·Prior treatment over the previous 30 days before screening with:
·Any extended-release opioids, OR
·Immediate-release opioids at greater than an average 40 mg morphine equivalent daily dose
·Received an experimental drug or used an experimental medical device within 30 days before screening or have participated in a previous study of CG5503
·Contraindications to, history of allergy to, or hypersensitivity to CG5503, oxycodone, hydromorphone, morphine, or fentanyl, or their excipients.
·Chronic systemic steroid therapy within 4-weeks before screening, excluding inhalers or a 1-time intraoperative dose
·Undergoing concomitant surgical procedures in addition to primary total hip replacement
·Will need postoperative Intensive Care Unit care
·Likely to require the use of disallowed analgesia or prohibited concomitant therapy during participation in the study
·Women who plan to become pregnant during the study or who are breast feeding


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

Health Condition(s) or Problem(s) studied

Pain
MedDRA version: 9.1 Level: LLT Classification code 10033371 Term: Pain

Intervention(s)

Product Name: CG5503/R331333
Product Code: CG5503/R331333
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Tapentadol
CAS Number: 175591-09-0
Current Sponsor code: CG5503/R331333
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: Capsule*
Route of administration of the placebo: Oral use

Product Name: CG5503/R331333
Product Code: CG5503/R331333
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Tapentadol
CAS Number: 175591-09-0
Current Sponsor code: CG5503/R331333
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: 75-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: CG5503/R331333
Product Code: CG5503/R331333
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Tapentadol
CAS Number: 175591-09-0
Current Sponsor code: CG5503/R331333
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: Capsule*
Route of administration of the placebo: Oral use

Trade Name: OxyNorm®
Product Name: OxyNorm®
Product Code: N02A A05
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: oxycodone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to determine the efficacy of CG5503 immediate release (IR) using the sum of pain intensity difference (SPID) over 48 hours compared to placebo, and to assess the safety and tolerability of multiple doses of CG5503 IR in subjects with acute pain following primary unilateral total hip replacement surgery over the double-blind period.

Primary end point(s): The primary efficacy endpoint for this study is the sum of pain intensity difference over 48 hours (SPID48). The SPID48 will be calculated as the weighted sum of the pain intensity difference (difference between baseline at qualifying period and current pain intensity) collected up to 48 hours.

Secondary Objective: o Comparison of the effect of CG5503 IR on the time to the first rescue pain medication during the double blind treatment period.
o Evaluation of the effect of CG5503 IR versus placebo with the distribution of responder rates for each time point (at 12, 24, 48, and 72 hours).
o Evaluation of the efficacy of CG5503 IR by examining the total effect on pain relief and pain intensity over the 72-hour double-blind period.
o Assessment of the Patient Global Impression of Change (PGIC) at the end of the double-blind treatment period.
o Evaluation of the adverse event rates across treatment groups in the double-blind treatment period (especially nausea and vomiting).

Secondary ID(s)

2006-004513-18-GB

R331333-PAI-3001/ KF5503/31

n/a