A Study to Evaluate the Efficacy and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain After Abdominal Hysterectomy

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

Sponsors

Lead Sponsor: Grünenthal GmbH

Collaborator: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Source Grünenthal GmbH
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).

Overall Status Completed
Start Date May 2007
Completion Date April 2008
Primary Completion Date February 2008
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity. Baseline to 24 hours after first intake of study drug
Secondary Outcome
Measure Time Frame
Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity Baseline value to 48 hours after first study drug intake.
Enrollment 854
Condition
Intervention

Intervention Type: Drug

Intervention Name: Morphine

Description: 20 mg IR; 4 - 6 hourly; Total 72 hours

Arm Group Label: Morphine

Intervention Type: Drug

Intervention Name: CG5503 IR

Description: 50mg; 4 - 6 hourly; Total 72 hours

Arm Group Label: Tapentadol 50 mg immediate release

Other Name: Tapentadol

Intervention Type: Drug

Intervention Name: CG5503 IR

Description: 75mg; 4 -6 hourly; Total 72 hours

Arm Group Label: Tapentadol 75 mg immediate release

Other Name: Tapentadol

Intervention Type: Drug

Intervention Name: CG5503 IR

Description: 100mg, 4 - 6 hourly; Total 72 hours

Arm Group Label: Tapentadol 100 mg immediate release

Other Name: Tapentadol

Intervention Type: Drug

Intervention Name: Placebo

Description: 4 - 6 hourly; Total 72 hours

Arm Group Label: Matched placebo

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;

Gender: Female

Minimum Age: 18 Years

Maximum Age: 80 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Tomasz Rechberger, Prof. Principal Investigator Samodzielny Publiczny Szpital
Location
Facility:
Site 13 | Bekescsaba, Hungary
Site 14 | Debrecen, Hungary
Site 15 | Komarom, Hungary
Site 12 | Nyíregyháza, Hungary
Site 16 | Riga, Latvia
Site 17 | Riga, Latvia
Site 18 | Riga, Latvia
Site 19 | Riga, Latvia
Site 27 | Katowice, Poland
Site 23 | Krakow, Poland
Site 24 | Lodz, Poland
Site 66 | Lodz, Poland
Site 22 | Lublin, Poland
Site 25 | Lublin, Poland
Site 26 | Ruda Slaska, Poland
Site 20 | Warszawa, Poland
Site 21 | Warszawa, Poland
Site 28 | Wroclaw, Poland
Site 33 | Brasov, Romania
Site 78 | Brasov, Romania
Site 29 | Bucharest, Romania
Site 30 | Bucharest, Romania
Site 31 | Bucharest, Romania
Site 32 | Bucharest, Romania
Site 34 | Bucharest, Romania
Site 35 | Bucharest, Romania
Site 36 | Bucharest, Romania
Site 76 | Bucharest, Romania
Site 75 | Craiova, Romania
Site 61 | Ploiesti, Romania
Site 71 | Belgorod, Russian Federation
Site 37 | Moscow, Russian Federation
Site 38 | Moscow, Russian Federation
Site 44 | Moscow, Russian Federation
Site 73 | Moscow, Russian Federation
Site 42 | St. Petersburg, Russian Federation
Site 43 | St. Petersburg, Russian Federation
Site 45 | Belgrade, Serbia
Site 47 | Belgrade, Serbia
Site 46 | Kragujevac, Serbia
Site 70 | Novi Sad, Serbia
Site 48 | Banská Bystrica, Slovakia
Site 51 | Bratislava, Slovakia
Site 52 | Bratislava, Slovakia
Site 62 | Kosice, Slovakia
Site 50 | Martin, Slovakia
Site 53 | Maribor, Slovenia
Site 64 | Donetsk, Ukraine
Site 55 | Kiev, Ukraine
Site 56 | Kiev, Ukraine
Site 58 | Kiev, Ukraine
Site 67 | Zaporizhya, Ukraine
Location Countries

Hungary

Latvia

Poland

Romania

Russian Federation

Serbia

Slovakia

Slovenia

Ukraine

Verification Date

October 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Number Of Arms 5
Arm Group

Label: Morphine

Type: Active Comparator

Label: Tapentadol 50 mg immediate release

Type: Experimental

Label: Tapentadol 75 mg immediate release

Type: Experimental

Label: Tapentadol 100 mg immediate release

Type: Experimental

Label: Matched placebo

Type: Placebo Comparator

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov