A Trial to Evaluate CG5503 Efficacy and Safety in Acute Pain After Bunionectomy

Study Description

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Brief Summary:

The main objective of this trial is to demonstrate the efficacy and safety of multiple-dose application of oral application of CG5503 IR 75mg compared to placebo and to assess safety and tolerability of CG5503 IR 75mg in subjects following bunionectomy.

This trial was performed based on a previously performed double-blind, placebo-controlled, multiple-dose trial in the same indication investigating 3 dose strengths CG5503 IR (50, 75 and 100 mg) published under PMID: 18851776.

Condition or disease	Intervention/treatment	Phase
Bunionectomy; Pain; Postoperative Pain; Acute Pain	Drug: CG5503 IR; Drug: Morphine; Drug: Placebo	Phase 3

Detailed Description:

Subjects undergoing bunionectomy 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. 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 trial is to investigate the effectiveness (level of pain control) and safety (side effects) of CG5503 IR 75mg compared with no drug (placebo) or one dose of morphine (an opioid commonly used to treat post-surgical pain). This trial is a randomized, double-blind (neither investigator nor patient will know which treatment was received), active- and placebo-controlled, parallel-group, multicenter trial to evaluate the treatment of acute pain after bunionectomy. The trial will include a blinded 72 hour inpatient phase immediately following bunionectomy, during which subjects will be treated with either 75-mg CG5503 IR, a placebo, or 30-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 trial hypothesis is that at least 1 dose strength of CG5503 will be different from placebo in controlling pain at 48 hours.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	291 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-blind, Parallel-group, Multi-center, Active- and Placebo-controlled Trial to Evaluate the Analgesic Efficacy and Safety of Multiple Doses of CG5503 IR for Postoperative Pain Following Bunionectomy
Study Start Date :	September 2007
Actual Primary Completion Date :	February 2008
Actual Study Completion Date :	February 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1; CG5503 IR 75mg 4 to 6 hourly for 72 hours	Drug: CG5503 IR; 75mg IR 4 - 6 hourly Total: 72 hours
Active Comparator: 2; Morphine IR 30 mg 4 to 6 hourly for 72 hours	Drug: Morphine; Morphine 30 mg IR 4 - 6 hourly Total: 72 hours
Placebo Comparator: 3; Matching placebo 4 to 6 hourly for 72 hours	Drug: Placebo; Placebo; 4 - 6 hourly; Total: 72 hours

Outcome Measures

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Primary Outcome Measures :

1. Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity. [ Time Frame: Baseline value to 48 hours after first study drug intake. ]
   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).

Secondary Outcome Measures :

1. Number of Participants Using Rescue Medication [ Time Frame: Baseline up to 72 hours after first study drug intake ]
   Number of participants who used at least one dose of rescue medication during the 72 hour double blind period.
2. Total Pain Relief (TOTPAR) [ Time Frame: Baseline to 48 hours after first study drug intake ]
   Total pain relief (TOTPAR) in the 48 hour period from the first dose of study drug. The subject was to indicate pain relief at rest in response to the following question: How much relief have you had from your starting pain? None = 0, A little = 1, Some = 2, A lot = 3 and Complete = 4. The theoretical maximum range of Total pain relief (TOTPAR)48 is from 0 (indicative of no pain relief) to 192. The higher the value the better the pain relief.
3. Sum of Pain Intensity Differences Over 6 Hours (SPID6) Relative to the Baseline Pain Intensity [ Time Frame: Baseline to 6 hours after intake of first study drug ]
   Pain Intensity assessed at predefined time points over a 6 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 (SPID6) is from -60 (indicative of an increase in pain) to 60 (indicative of a decrease in pain).
4. Sum of Pain Intensity Differences Over 12 Hours (SPID12) Relative to the Baseline Pain Intensity [ Time Frame: Baseline to 12 hours after first study drug intake ]
   Pain Intensity assessed at predefined time points over a 12 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 (SPID12) is from -120 (indicative of an increase in pain) to 120 (indicative of a decrease in pain).
5. Sum of Pain Intensity Differences Over 24 Hours (SPID24) Relative to the Baseline Pain Intensity [ Time Frame: Baseline to 24 hours after first study drug intake ]
   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).
6. Sum of Pain Intensity Differences Over 72 Hours (SPID72) Relative to the Baseline Pain Intensity [ Time Frame: Baseline to 72 hours after first intake of study drug ]
   Pain Intensity assessed at predefined time points over a 72 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 (SPID72) is from -720 (indicative of an increase in pain) to 720 (indicative of a decrease in pain).

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Male and female subjects between 18 and 80 years of age;
• Scheduled to undergo primary unilateral first metatarsal bunionectomy;
• Anesthesiological and surgical procedures performed according to protocol;
• Moderate or severe baseline pain following bunionectomy on a VRS within 9 hours of termination of the continuous popliteal sciatic block or systemic analgesia;
• Pain following bunionectomy of at least 4 on an 11-point NRS within 9 hours of termination of the continuous popliteal sciatic block or systemic analgesia; American Society of Anesthesiologists (ASA) classification I-III.

Exclusion Criteria:

• History of seizure disorder;
• History of alcohol, medication or drug dependency, unstable psychological personality requiring intermittent or permanent treatment; severely impaired renal function, moderately or severely impaired hepatic function;
• Contraindications to, or history of allergy or hypersensitivity to CG5503, oxycodone, morphine, fentanyl hydrocodone, acetaminophen, heparin, or any compound planned to be used during the anesthesia, or their excipients;
• Pre-operative use within 12h prior to surgery or peri-operative use of non- steroidal anti-inflammatory drugs (NSAIDs);
• Treated regularly with opioid analgesic or NSAIDs within 30 days prior to screening;

Contacts and Locations

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Locations

United States, Maryland
Site 104
Pasadena, Maryland, United States, 21122
United States, Texas
Site 101
Austin, Texas, United States, 78705
Site 102
Houston, Texas, United States, 77081
Site 105
San Antonio, Texas, United States, 78229
Site 103
San Marcos, Texas, United States, 78666
United States, Utah
Site 106
Salt Lake City, Utah, United States, 84117

Sponsors and Collaborators

Grünenthal GmbH

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

Investigators

Principal Investigator:	Stephen E Daniels, DO	Premier Research Group (formerly SCIREX Corporation)

More Information

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Responsible Party:	Grünenthal GmbH
ClinicalTrials.gov Identifier:	NCT00609466 History of Changes
Other Study ID Numbers:	574139
First Posted:	February 7, 2008
Results First Posted:	November 25, 2009
Last Update Posted:	November 16, 2011
Last Verified:	November 2011

Keywords provided by Grünenthal GmbH:

Opioid; Central acting analgesic; CG5503 IR; Postoperative pain	Bunionectomy; Morphine; Placebo

Additional relevant MeSH terms:

Pain, Postoperative; Acute Pain; Pain; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Signs and Symptoms	Morphine; Analgesics; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents