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

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.

Study Overview

• Status: Completed
• Conditions: Hysterectomy; Postoperative
• Intervention / Treatment: Drug: Morphine; Drug: CG5503 IR; Drug: CG5503 IR; Drug: CG5503 IR; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 854
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Bekescsaba, Hungary
    • Site 13
  • Debrecen, Hungary
    • Site 14
  • Komarom, Hungary
    • Site 15
  • Nyíregyháza, Hungary
    • Site 12
• Latvia
  • Riga, Latvia
    • Site 16
  • Riga, Latvia
    • Site 17
  • Riga, Latvia
    • Site 18
  • Riga, Latvia
    • Site 19
• Poland
  • Katowice, Poland
    • Site 27
  • Krakow, Poland
    • Site 23
  • Lodz, Poland
    • Site 24
  • Lodz, Poland
    • Site 66
  • Lublin, Poland
    • Site 22
  • Lublin, Poland
    • Site 25
  • Ruda Slaska, Poland
    • Site 26
  • Warszawa, Poland
    • Site 20
  • Warszawa, Poland
    • Site 21
  • Wroclaw, Poland
    • Site 28
• Romania
  • Brasov, Romania
    • Site 33
  • Brasov, Romania
    • Site 78
  • Bucharest, 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
  • Craiova, Romania
    • Site 75
  • Ploiesti, Romania
    • Site 61
• Russian Federation
  • Belgorod, Russian Federation
    • Site 71
  • Moscow, Russian Federation
    • Site 44
  • Moscow, Russian Federation
    • Site 37
  • Moscow, Russian Federation
    • Site 38
  • Moscow, Russian Federation
    • Site 73
  • St. Petersburg, Russian Federation
    • Site 42
  • St. Petersburg, Russian Federation
    • Site 43
• Serbia
  • Belgrade, Serbia
    • Site 45
  • Belgrade, Serbia
    • Site 47
  • Kragujevac, Serbia
    • Site 46
  • Novi Sad, Serbia
    • Site 70
• Slovakia
  • Banská Bystrica, Slovakia
    • Site 48
  • Bratislava, Slovakia
    • Site 51
  • Bratislava, Slovakia
    • Site 52
  • Kosice, Slovakia
    • Site 62
  • Martin, Slovakia
    • Site 50
• Slovenia
  • Maribor, Slovenia
    • Site 53
• Ukraine
  • Donetsk, Ukraine
    • Site 64
  • Kiev, Ukraine
    • Site 55
  • Kiev, Ukraine
    • Site 56
  • Kiev, Ukraine
    • Site 58
  • Zaporizhya, Ukraine
    • Site 67

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Matched placebo	Drug: Placebo; 4 - 6 hourly; Total 72 hours
Active Comparator: Morphine	Drug: Morphine; 20 mg IR; 4 - 6 hourly; Total 72 hours
Experimental: Tapentadol 50 mg immediate release	Drug: CG5503 IR; 50mg; 4 - 6 hourly; Total 72 hours; Other Names: Tapentadol; Drug: CG5503 IR; 75mg; 4 -6 hourly; Total 72 hours; Other Names: Tapentadol; Drug: CG5503 IR; 100mg, 4 - 6 hourly; Total 72 hours; Other Names: Tapentadol
Experimental: Tapentadol 75 mg immediate release	Drug: CG5503 IR; 50mg; 4 - 6 hourly; Total 72 hours; Other Names: Tapentadol; Drug: CG5503 IR; 75mg; 4 -6 hourly; Total 72 hours; Other Names: Tapentadol; Drug: CG5503 IR; 100mg, 4 - 6 hourly; Total 72 hours; Other Names: Tapentadol
Experimental: Tapentadol 100 mg immediate release	Drug: CG5503 IR; 50mg; 4 - 6 hourly; Total 72 hours; Other Names: Tapentadol; Drug: CG5503 IR; 75mg; 4 -6 hourly; Total 72 hours; Other Names: Tapentadol; Drug: CG5503 IR; 100mg, 4 - 6 hourly; Total 72 hours; Other Names: Tapentadol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity.	Pain Intensity assessed at predefined time points over a 24 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Differences calculated as [baseline-post baseline] at each predefined time point. The theoretical maximum range of Sum of pain intensity differences (SPID24) is from -240 (indicative of an increase in pain) to 240 (indicative of a decrease in pain, assuming patients start with a baseline value of 10 and all subsequent values will be 0).	Baseline to 24 hours after first intake of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity	Pain Intensity assessed at predefined time points over a 48 hour period using an 11-point Numeric Rating Scale (NRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Differences calculated as [baseline-post baseline] at each predefined time point. The theoretical maximum range of Sum of pain intensity differences (SPID48) is from -480 (indicative of an increase in pain) to 480 (indicative of a decrease in pain, assuming patients start with a baseline value of 10 and all subsequent values will be 0).	Baseline value to 48 hours after first study drug intake.

Collaborators and Investigators

• Sponsor: Grünenthal GmbH
• Collaborators: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Investigators: Principal Investigator: Tomasz Rechberger, Prof., Samodzielny Publiczny Szpital

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 23, 2007
• First Submitted That Met QC Criteria: May 23, 2007
• First Posted (Estimate): May 24, 2007

Study Record Updates

• Last Update Posted (Actual): October 28, 2019
• Last Update Submitted That Met QC Criteria: October 9, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Opioid; Morphine; Placebo; Central acting analgesic; CG5503 IR; Pain postoperative; Abdomen acute
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Morphine; Tapentadol
• Other Study ID Numbers: 731200