An evaluation of the effectiveness and tolerability of tapentadol hydrochloride prolonged release, and tapentadol hydrochloride immediate release on demand, in subjects with severe chronic pain due to osteoarthritis of the knee taking WHO Step III analgesics but showing a lack of tolerability.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-010425-39-GB
• Date of registration: 29/05/2009
• Prospective Registration: Yes
• Primary sponsor: Grünenthal GmbH
• Public title: An evaluation of the effectiveness and tolerability of tapentadol hydrochloride prolonged release, and tapentadol hydrochloride immediate release on demand, in subjects with severe chronic pain due to osteoarthritis of the knee taking WHO Step III analgesics but showing a lack of tolerability.
• Scientific title: An evaluation of the effectiveness and tolerability of tapentadol hydrochloride prolonged release, and tapentadol hydrochloride immediate release on demand, in subjects with severe chronic pain due to osteoarthritis of the knee taking WHO Step III analgesics but showing a lack of tolerability.
• Date of first enrolment: 23/09/2009
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010425-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Denmark, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Key inclusion criteria (general)
Subjects have signed an Informed Consent Form indicating that they understand the purpose of and the procedures required for the trial and are willing to participate in it.
Subjects are men or non-pregnant, non-lactating women. Sexually active women must be postmenopausal, 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. Women of childbearing potential must have a negative pregnancy test at screening.
Subjects must be appropriately communicative to verbalize and to differentiate with regard to location and intensity of the pain.
Key inclusion criteria (trial specific) - at the Screening Visit
Subjects must be at least 40 years of age.
Subjects must have a diagnosis of osteoarthritis of the knee based on the American College of Rheumatology (ACR) classification criteria:
Knee pain and Radiographic osteophytes or Knee pain and Aged 40 years or above, and Morning stiffness of 30 minutes of duration or more, and Crepitus on motion.
Subjects must have pain at the reference joint which has been present for at least 3 months.
Subject’s pain must require a strong analgesic (defined as WHO Step III) as judged by the Investigator.
Subjects must be taking a WHO Step III analgesic on a daily basis for at least 2 weeks prior to the Screening Visit.
Subjects must have responded to the WHO Step III analgesic, i.e., Subjects must have a confirmed average pain intensity score (NRS 3) of ?5 points during the last 3 days prior to the Screening Visit.
Subjects must report opioid-related side effects as the reason to change their analgesic.
Subjects must report a rate of satisfaction with their previous analgesic regimen not exceeding “fair” on a subject satisfaction with treatment scale (5-point VRS).

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:
Key exclusion criteria (general)
Presence of a clinically significant disease or laboratory findings that in the Investigator’s opinion may affect efficacy or safety assessments.
Presence of active systemic or local infection, that may, in the opinion of the Investigator, affect the efficacy, quality of life/function or safety assessments.
History of alcohol or drug abuse, or suspicion thereof in the Investigator’s judgment.
Presence of concomitant autoimmune inflammatory conditions.
Known history of or laboratory values reflecting severe renal impairment.
Known history of moderately or severely impaired hepatic function.
History of or active hepatitis B or C within the past 3 months or history of HIV infection.
History of seizure disorder or epilepsy.
Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm. Severe traumatic brain injury within 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or post-traumatic amnesia lasting more than 24 h) or residual sequelae suggesting transient changes in consciousness.
Pregnant or breast-feeding.
History of allergy to, or hypersensitivity to tapentadol hydrochloride or its excipients, or contraindications related to tapentadol hydrochloride including:
Subjects with acute or severe bronchial asthma or hypercapnia.
Subjects who have or are suspected of having paralytic ileus.
Employees of the Investigator or trial site, with direct involvement in this trial or other trials under the direction of the Investigator or trial site, as well as family members of employees of the Investigator.
Participation in another trial concurrently or within 4 weeks prior to the Screening Visit.
Known to or suspected of not being able to comply with the protocol and the use of the IMPs.
Use of monoamine oxidase inhibitors within 14 days before the Screening Visit.
Non-stable dosing of selective serotonin reuptake inhibitors within 30 days before the Screening Visit (Doses must remain stable during the trial).
Key exclusion criteria (trial specific)
Osteoarthritis in a flare state.
Use of intra-articular injections of hyaluronic acid in the reference joint within 3 months before the Screening Visit.
Presence of conditions other than osteoarthritis of the reference joint that could confound the assessment or self-evaluation of pain, e.g., anatomical deformities, significant skin conditions such as abscess or syndromes with widespread pain such as fibromyalgia. Subjects with osteoarthritis at joints other than the reference joint will not be excluded as long as the reference joint is the source of main pain and disability.
History and clinical signs at the reference joint of crystal-induced (e.g., gout, pseudo-gout), metabolic, infectious and autoimmune disease.
Any painful procedures during the trial (e.g., major surgery, including the reference joint) that may, in the opinion of the Investigator, affect the efficacy or safety assessments.
Pending litigation due to chronic pain or disability.



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

Health Condition(s) or Problem(s) studied

Pain due to Osteoarthritis
MedDRA version: 9.1 Level: LLT Classification code 10031161 Term: Osteoarthritis

Intervention(s)

Product Name: Tapentadol 50 mg film-coated tablet
Product Code: CG5503
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503; R331333;
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Tapentadol 50 mg prolonged release tablet
Product Code: CG5503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503; R331333;
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Tapentadol 100 mg prolonged release tablet
Product Code: CG5503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503; R331333;
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: Tapentadol 150 mg prolonged release tablet
Product Code: CG5503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503; R331333;
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Name: Tapentadol 200 mg prolonged release tablet
Product Code: CG5503
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Tapentadol hydrochloride
CAS Number: 175591-09-0
Current Sponsor code: CG5503; R331333;
Other descriptive name: 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol-hydrochloride
Conce

Primary Outcome(s)

Main Objective: Primary objective is to evaluate the effectiveness, tolerability, and safety of tapentadol hydrochloride PR in subjects with chronic pain due to osteoarthritis of the knee pretreated with WHO Step III opioids but showing lack of tolerability.

Primary end point(s): The primary endpoint is defined as responder rate 1, the percentage of subjects with the same or less pain (on the NRS-3) at Week 6 compared with Week -1.

Secondary Objective: Evaluate equipotency ratios of tapentadol hydrochloride PR and different WHO Step III analgesics calculated using morphine equivalent doses.
Evaluate the conversion of subjects from previous WHO Step III analgesics to tapentadol hydrochloride PR.
Evaluate the titration of tapentadol hydrochloride PR in clinical practice.
Evaluate a potential reduction in the need for WHO Step I analgesics and co-analgesics under tapentadol hydrochloride PR treatment (sparing effect).
Evaluate a potential reduction in the need for medications (antiemetics and laxatives) to treat opioid-related adverse events in subjects previously treated with WHO Step III opioid analgesics.
Evaluate the efficacy and tolerability of tapentadol hydrochloride PR versus previous treatment for osteoarthritis pain.
Evaluate the impact of tapentadol hydrochloride PR on function and quality of life parameters (subject-reported outcomes) in subjects with pain due to osteoarthritis of the knee.

Secondary ID(s)

KF5503/43