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

Hysterectomy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00478023
• Other study ID #: 731200
• Status: Completed
• Phase: Phase 3
• Start date: May 2007
• Est. completion date: April 2008

Study information

• Verified date: October 2019
• Source: Grünenthal GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 854
• Est. completion date: April 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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;

Related Conditions & MeSH terms

• Hysterectomy
• Postoperative

Intervention

Drug:
• Morphine
20 mg IR; 4 - 6 hourly; Total 72 hours
• CG5503 IR
50mg; 4 - 6 hourly; Total 72 hours
• CG5503 IR
75mg; 4 -6 hourly; Total 72 hours
• CG5503 IR
100mg, 4 - 6 hourly; Total 72 hours
• Placebo
4 - 6 hourly; Total 72 hours

Locations

Country	Name	City	State
Hungary	Site 13	Bekescsaba
Hungary	Site 14	Debrecen
Hungary	Site 15	Komarom
Hungary	Site 12	Nyíregyháza
Latvia	Site 16	Riga
Latvia	Site 17	Riga
Latvia	Site 18	Riga
Latvia	Site 19	Riga
Poland	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
Romania	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
Russian Federation	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
Serbia	Site 45	Belgrade
Serbia	Site 47	Belgrade
Serbia	Site 46	Kragujevac
Serbia	Site 70	Novi Sad
Slovakia	Site 48	Banská Bystrica
Slovakia	Site 51	Bratislava
Slovakia	Site 52	Bratislava
Slovakia	Site 62	Kosice
Slovakia	Site 50	Martin
Slovenia	Site 53	Maribor
Ukraine	Site 64	Donetsk
Ukraine	Site 55	Kiev
Ukraine	Site 56	Kiev
Ukraine	Site 58	Kiev
Ukraine	Site 67	Zaporizhya

Sponsors (2)

Lead Sponsor	Collaborator
Grünenthal GmbH	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Countries where clinical trial is conducted

Hungary,  Latvia,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  Slovenia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.