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

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT00478023
First received: May 23, 2007
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Hysterectomy
Postoperative
Drug: Morphine
Drug: CG5503 IR
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity. [ Time Frame: Baseline to 24 hours after first intake of study drug ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity [ Time Frame: Baseline value to 48 hours after first study drug intake. ] [ Designated as safety issue: No ]
    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).


Enrollment: 854
Study Start Date: May 2007
Study Completion Date: April 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Tapentadol
Experimental: Tapentadol 75 mg immediate release Drug: CG5503 IR
75mg; 4 -6 hourly; Total 72 hours
Other Name: Tapentadol
Experimental: Tapentadol 100 mg immediate release Drug: CG5503 IR
100mg, 4 - 6 hourly; Total 72 hours
Other Name: Tapentadol
Placebo Comparator: Matched placebo Drug: Placebo
4 - 6 hourly; Total 72 hours

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478023

  Show 52 Study Locations
Sponsors and Collaborators
Grünenthal GmbH
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Principal Investigator: Tomasz Rechberger, Prof. Samodzielny Publiczny Szpital
  More Information

No publications provided

Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT00478023     History of Changes
Other Study ID Numbers: 731200
Study First Received: May 23, 2007
Results First Received: December 16, 2009
Last Updated: December 20, 2013
Health Authority: Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Croatia: Ministry of Health and Social Care
Hungary: National Institute of Pharmacy
Latvia: State Agency of Medicines
Poland: Ministry of Health
Romania: Ministry of Public Health
Russia: Ministry of Health of the Russian Federation
Slovenia: Agency for Medicinal Products - Ministry of Health
Slovakia: State Institute for Drug Control
Ukraine: Ministry of Health

Keywords provided by Grünenthal GmbH:
Opioid
Central acting analgesic
Pain postoperative
Abdomen acute
CG5503 IR
Morphine
Placebo

Additional relevant MeSH terms:
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014