A Study to Evaluate CG5503 in the Treatment of Chronic Tumor Related Pain Compared With Placebo and Morphine - Full Text View

Sponsored by:	Grünenthal GmbH
Information provided by:	Grünenthal GmbH
ClinicalTrials.gov Identifier:	NCT00472303

Purpose

The Purpose of this study is to determine whether CG5503 is effective and safe in the treatment of chronic tumor related pain compared to placebo. In addition CG5503 will also be compared to morphine SR.

Condition	Intervention	Phase
Tumor Pain	Drug: CG5503 ER Drug: Placebo to match CG5503 Drug: Morphine Sulphate CR Drug: Placebo to match Morphine Sulphate CR	Phase III

MedlinePlus related topics: Cancer

Drug Information available for: Tapentadol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	A Randomized Withdrawal, Active- and Placebo-Controlled, Double-Blind, Multi-Center Phase III Trial Assessing Safety and Efficacy of Oral CG5503 PR* in Subjects With Moderate to Severe Chronic Malignant Tumor-Related Pain

Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:

Proportion of subjects classified as responders. Responders are subjects who meet all of the following criteria: • Complete 28 days of the Maintenance phase • Have a mean pain intensity < 5.0 point on an 11-poi [ Time Frame: End of trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Daily pain intensity (11-point NRS) (current pain intensity, average pain intensity in the last 24 hours), use of rescue medication (frequency and amount) and incidence and time to discontinuation fr [ Time Frame: End of trial ] [ Designated as safety issue: No ]

Estimated Enrollment:	573
Study Start Date:	July 2007
Estimated Study Completion Date:	July 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Entering the titration phase subjects will be randomized into either ARM A or ARM C, with a ratio of 2:1 respectively. In the maintenance phase subjects in ARM A will be re-randomized into either ARM A or ARM B, with a ratio of 1:1.	Drug: CG5503 ER Tablet taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses. Titration phase: Starting at 100 mg, increasing at a minimum of 3 day intervals by 50 mg, with a maximum dose of 250 mg. Maintenance phase: continuing on dose level established in titration phase. Drug: Placebo to match Morphine Sulphate CR Capsule taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses
B: Placebo Comparator In the maintenance phase subjects in ARM A will be re-randomized into either ARM A or ARM B with a ratio of 1:1.	Drug: Placebo to match CG5503 Tablet taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses Drug: Placebo to match Morphine Sulphate CR Capsule taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses
C: Active Comparator Entering the titration phase subjects will be randomized into either ARM A or ARM B, with a ratio of 2:1 respectively. In the maintenance phase subjects in ARM C will continue in ARM C	Drug: Placebo to match CG5503 Tablet taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses Drug: Morphine Sulphate CR Capsule taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses. Titration phase: Starting at 40 mg, increasing at a minimum of 3 days intervals by 20 mg, with a maximum dose of 100 mg. Maintenance phase: continuing on dose level established in titration phase.

Detailed Description:

Normally chronic tumor related 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 prolonged release (PR) 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 PR compared with no drug (placebo) and corresponding dose of morphine (an opioid commonly used to treat tumor related 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.

The trial includes a 2 week titration phase starting with either 40 mg morphine (PR) bid or 100 mg CG5503 PR bid. Based on effectiveness and side effects subjects can up-titrate in steps of 50 mg CG5503 PR (20 mg morphine PR) to a maximal dose of 250 mg CG5503 PR bid or 100 mg morphine PR bid. If subjects meet the stabilisation criteria at the end of the titration phase they will be re-randomized to either placebo or active treatment and will continue 4 weeks at the last dose level in the maintenance phase.

Assessments of pain relief include the pain intensity numeric rating scale (NRS), 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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Male and non-pregnant, non-lactating female subjects.
Of at least 18 years of age with chronic malignant tumor-related pain with a mean pain intensity (NRS) of 5 points or higher.
Subjects who are opioid-naïve or pretreated with an equianalgesic dose range equivalent of up to 160 mg oral morphine per day and are dissatisfied with prior treatment.
Women must be postmenopausal, surgically sterile, or practicing or agree to practice an effective method of birth control throughout the trial.

Exclusion Criteria

Key Exclusion Criteria:

Subjects will be excluded from the study if they have a history of seizure disorder or epilepsy;
cerebral metastases;
history of alcohol or drug abuse;
uncontrolled hypertension,
clinical laboratory values reflecting severe renal insufficiency,
moderate or severe hepatic impairment,
hepatitis B or C, HIV,
thrombopenia, leukopenia or hypercalcemia,
currently treated with radiotherapy,
pain inducing chemotherapy,
anti-parkinsonian drugs, neuroleptics, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitor (SNRI) or any other analgesic therapy than investigational medication or rescue medication during the trial.
selective serotonin reuptake inhibitor (SSRI) treatments are allowed if taken for at least 30 days before the screening period of the study at an unchanged dose.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00472303

Contacts

Contact: Claudia Leinweber

+49 (0)241-569 ext 2509

Clinical-Trials@grunenthal.com

Show 78 Study Locations

Sponsors and Collaborators

Grünenthal GmbH

Investigators

Principal Investigator:

Hans Georg Kress, Dr.

Clinic of Anaesthesiology and Pain Management, AKH Vienna

More Information

Responsible Party:	Grünenthal GmbH ( Grünenthal GmbH )
Study ID Numbers:	761101
Study First Received:	May 10, 2007
Last Updated:	July 18, 2008
ClinicalTrials.gov Identifier:	NCT00472303
Health Authority:	Bulgaria: Bulgarian Drug Agency; Czech Republic: State Institute of Drug Control; Hungary: National Institute of Pharmacy; Poland: Central Register of Clinical Trials; Romania: National Medicines Agency; Russia: The Ministry of Health and Scocial Development of the Russian Federation; Serbia: Medicines and Medical Devices Agency of Sebia; Slovakia: State Institute of Drug control; Germany: Bundesinstitut für Arzneimittel und Medizinprodukte; Austria: Österreichische Agentur für Gesundheit und Ernährungssicherheit; Switzerland: Swissmedic, Schweizerisches Heilmittelinstitut; Italy: Local Hospital Boards only; Croatia: Ministry of Health and Social Welfare; Spain: Agencia Espanola de Medicamentos y Productos Sanitarios

Keywords provided by Grünenthal GmbH:

Opioid
Central acting analgesic
CG5503 PR
Tumor related pain

Cancer related pain
Morphine
Pain assessment
Placebo

Study placed in the following topic categories:

Morphine
Pain

Additional relevant MeSH terms:

Sensory System Agents
Therapeutic Uses
Physiological Effects of Drugs
Central Nervous System Depressants
Narcotics

Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Pharmacologic Actions
Analgesics, Opioid

ClinicalTrials.gov processed this record on January 16, 2009