Clinical trial NCT00478023: A Study to Evaluate the Efficacy and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain After Abdominal Hysterectomy
Official title: A Randomized, Double-blind, Parallel-arm, Placebo- and Comparator- Controlled Trial of the Efficacy and Safety of Multiple Doses of Immediate-release (IR) CG5503 for Postoperative Pain Following Abdominal Hysterectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hysterectomy
Postoperative
Keywords: Opioid
Central acting analgesic
Pain postoperative
Abdomen acute
CG5503 IR
Morphine
Placebo
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2007-05-24
Enrollment: 854
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of this study is to demonstrate the efficacy and safety of multiple-dose application of three different oral doses of CG5503 IR (tapentadol immediate release) compared to placebo in women undergoing abdominal hysterectomy.

Detailed description: Subjects undergoing abdominal hysterectomy often experience moderate to severe acute pain post-surgery. Normally such pain is controlled when subjects receive repeated doses of opioid analgesics. However, opioid therapy is commonly associated with side effects such as nausea, vomiting, sedation, constipation, addiction, tolerance, and respiratory depression. Tapentadol (CG5503), a newly synthesized drug with an immediate release (IR) formulation, also acts as a centrally acting pain reliever but has a dual mode of action. The aim of this study is to investigate the effectiveness (level of pain control) and safety (side effects) of 3 dose levels of CG5503 IR compared with no drug (placebo) or one dose level of morphine (an opioid commonly used to treat post-surgical pain). This study is a randomized, double-blind (neither investigator nor patient will know which treatment was received), active- and placebo-controlled, parallel-group, multicenter study to evaluate the treatment of acute pain after abdominal hysterectomy. The study will include a blinded 72 hour in-patient phase immediately following hysterectomy, during which subjects will be treated with either 50-, 75-, or 100-mg CG5503 IR, a matched placebo, or 20-mg morphine, and pain relief will be periodically assessed. Assessments of pain relief include the pain intensity numeric rating scale (PI), pain relief numeric rating scale (PAR), and patient global impression of change scale (PGIC). Safety evaluations include monitoring of adverse events, physical examinations, and clinical laboratory tests. Venous blood samples will be collected for the determination of serum concentrations of CG5503 and morphine. The alternative study hypothesis is that at least 1 dose strength of CG5503 will be different from placebo in controlling pain at 24 hours (using the mean SPID at 24 hours).

Eligibility criteria: Inclusion Criteria:

* Female between 18 and 80 years of age;
* Scheduled to undergo an abdominal hysterectomy with or without bilateral salpingo-oophorectomy due to uterine leiomyomas, or dysfunctional uterine bleeding or endometrial hyperplasia;
* Anesthesiological and surgical procedures performed according to protocol;
* Moderate or severe baseline pain following hysterectomy on a Verbal Rating Scale (VRS) within 6 hours following the last possible application of morphine subcutaneous;
* Pain following hysterectomy of at least 4 on an 11-point Numeric Rating Scale (NRS) within 6 hours following the last possible application of morphine subcutaneous;
* American Society of Anesthesiologists (ASA) classification I-III.

Exclusion Criteria:

* Vaginal hysterectomy;
* Ongoing or known history of painful endometriosis;
* Known or suspected chronic pelvic pain syndrome;
* Previous abdominal or pelvic open surgery;
* History of seizure disorder or epilepsy;
* History of alcohol or drug abuse;
* Evidence of active infections that may spread to other areas of the body;
* severely impaired renal function, moderately or severely impaired hepatic function,
* Allergy or hypersensitivity to oxycodone, morphine, fentanyl hydromorphone, heparin, or any compound planned to be used during the anesthesia;
* Serious complication during surgery and up to randomization;
* Pre-operative use within 12hours prior to surgery or peri-operative use of non-steroidal anti-inflammatory drugs (NSAIDs);
* Treated regularly with opioid analgesic or non-steroidal anti-inflammatory drugs (NSAIDs) within 30 days prior to screening;

Primary outcomes:
measure: Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity.
timeFrame: Baseline to 24 hours after first intake of study drug
Secondary outcomes:
measure: Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity
timeFrame: Baseline value to 48 hours after first study drug intake.
Other outcomes:
Locations:
city: Bekescsaba
country: Hungary
facility: Site 13
city: Debrecen
country: Hungary
facility: Site 14
city: Komarom
country: Hungary
facility: Site 15
city: Nyíregyháza
country: Hungary
facility: Site 12
city: Riga
country: Latvia
facility: Site 16
city: Riga
country: Latvia
facility: Site 17
city: Riga
country: Latvia
facility: Site 18
city: Riga
country: Latvia
facility: Site 19
city: Katowice
country: Poland
facility: Site 27
city: Krakow
country: Poland
facility: Site 23
city: Lodz
country: Poland
facility: Site 24
city: Lodz
country: Poland
facility: Site 66
city: Lublin
country: Poland
facility: Site 22
city: Lublin
country: Poland
facility: Site 25
city: Ruda Slaska
country: Poland
facility: Site 26
city: Warszawa
country: Poland
facility: Site 20
city: Warszawa
country: Poland
facility: Site 21
city: Wroclaw
country: Poland
facility: Site 28
city: Brasov
country: Romania
facility: Site 33
city: Brasov
country: Romania
facility: Site 78
city: Bucharest
country: Romania
facility: Site 29
city: Bucharest
country: Romania
facility: Site 30
city: Bucharest
country: Romania
facility: Site 31
city: Bucharest
country: Romania
facility: Site 32
city: Bucharest
country: Romania
facility: Site 34
city: Bucharest
country: Romania
facility: Site 35
city: Bucharest
country: Romania
facility: Site 36
city: Bucharest
country: Romania
facility: Site 76
city: Craiova
country: Romania
facility: Site 75
city: Ploiesti
country: Romania
facility: Site 61
city: Belgorod
country: Russian Federation
facility: Site 71
city: Moscow
country: Russian Federation
facility: Site 37
city: Moscow
country: Russian Federation
facility: Site 38
city: Moscow
country: Russian Federation
facility: Site 44
city: Moscow
country: Russian Federation
facility: Site 73
city: St. Petersburg
country: Russian Federation
facility: Site 42
city: St. Petersburg
country: Russian Federation
facility: Site 43
city: Belgrade
country: Serbia
facility: Site 45
city: Belgrade
country: Serbia
facility: Site 47
city: Kragujevac
country: Serbia
facility: Site 46
city: Novi Sad
country: Serbia
facility: Site 70
city: Banská Bystrica
country: Slovakia
facility: Site 48
city: Bratislava
country: Slovakia
facility: Site 51
city: Bratislava
country: Slovakia
facility: Site 52
city: Kosice
country: Slovakia
facility: Site 62
city: Martin
country: Slovakia
facility: Site 50
city: Maribor
country: Slovenia
facility: Site 53
city: Donetsk
country: Ukraine
facility: Site 64
city: Kiev
country: Ukraine
facility: Site 55
city: Kiev
country: Ukraine
facility: Site 56
city: Kiev
country: Ukraine
facility: Site 58
city: Zaporizhya
country: Ukraine
facility: Site 67
Study officials:
affiliation: Samodzielny Publiczny Szpital
name: Tomasz Rechberger, Prof.
role: PRINCIPAL_INVESTIGATOR
References: