A Study to Evaluate the Effectiveness and Safety of CG5503 in the Treatment of Chronic Tumor Related Pain Compared With Placebo and Morphine

Condition(s) targeted: Tumors; Pain

Intervention: CG5503 ER (Drug); Placebo to match CG5503 (Drug); Morphine Sulphate CR (Drug); Placebo to match Morphine Sulphate CR (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Grünenthal GmbH

Official(s) and/or principal investigator(s):
P. Poulain, Dr., Principal Investigator, Affiliation: Institut Gustave Roussy

Overall contact:
Claudia Leinweber, Email: Clinical-Trials@grunenthal.com

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.

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. *PR Means Prolonged Release and is the Recommended Nomenclature for Use in EU. ER Means Extended Release and is the Recommended Nomenclature for Use in USA. "PR" is Synonymous With "ER" and is Interchangeable in the Protocol.

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: • Complete 28 days of the Maintenance phase • Have a mean pain intensity < 5.0 point on an 11-point NRS during the Maintenance phase • Do not use more than 2.0 doses of rescue medication/day on average during the Maintenance phase

Secondary outcome: •Daily pain intensity (11-point NRS) scores (current pain intensity, average pain intensity in the last 24 hours). •Use of rescue medication (frequency and amount). •Incidence and time to discontinuation from treatment due to adverse events (

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 (ER) 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 ER 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 45 mg morphine sulfate CR bid or 100 mg CG5503 ER bid. Based on effectiveness and side effects subjects can up-titrate in steps of 50 mg CG5503 ER or 15 mg morphine sulfate CR to a maximal dose of 250 mg CG5503 ER bid or 90 mg morphine sulfate CR bid respectively. 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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- A signed informed consent document.

- Male and non-pregnant, non-lactating female subjects.

- Female subjects must be post menopausal, surgically sterile, or practicing an

effective method of birth control and continue to do so throughout the trial.

- At least 18 years of age.

- Have chronic malignant tumor-related pain

- Are opioid-naïve or have been pretreated with an equianalgesic dose range equivalent

of up to 160 mg oral morphine per day and are dissatisfied with prior treatment.

- Have a mean pain intensity of >= 5 points (11-point NRS).

- Have expected course of the disease and the pain that will permit compliance with the

trial protocol over the entire trial period

Exclusion Criteria:

- Have a life-long history of seizure disorder or epilepsy.

- Have had any of the following within one year: mild/moderate traumatic brain injury,

stroke, and transient ischemic attack.

- Have had severe traumatic brain injury within 15 years (consisting of ≥ 1 of the

following: brain contusion, intracranial hematoma, and either unconsciousness or post-traumatic amnesia lasting for more than 24 hours) or residual sequelae suggesting transient changes in consciousness.

- Have a known history and/or presence of cerebral metastases.

- Have moderately or severely impaired hepatic function.

- Have laboratory values reflecting inadequate hepatic function.

- Have thrombopenia, leucopenia or hyperclicemia

- Have severely impaired renal function.

- Having uncontrolled hypertension

- Having clinically relevant history of hypersensitivity, allergy or contraindications

to morphine or any of the excipients.

- Have chronic hepatitis B or C, or HIV.

- Subjects currently undergoing the following concomitant therapy: radiotherapy, pain

inducing chemotherapy, anti-parkinsonian drugs, neuroleptics, monoamine oxidase inhibitors, serotonin norepinephrine re-uptake inhibitors (SNRI) or any other analgesic therapy than investigational medication or rescue medication during the trial. Selective serotonin re-uptake inhibitor (SSRI) treatments are allowed if taken for at least 30 days before the screening period of the trial at an unchanged dose.

Claudia Leinweber, Email: Clinical-Trials@grunenthal.com

Investigator 7, Ciudad de Buenos Aires, Argentina; Withdrawn

Investigator 9, Ciudad de Buenos Aires, Argentina; Recruiting

Investigator 17, Ciudad Autonoma de Buenos Aires, Argentina; Recruiting

Argentina 18, Ciduad Autonoma de Buenos Aires, Argentina; Not yet recruiting

Investigator 19, Ciudad Autonoma de Buenos Aires, Argentina; Not yet recruiting

Investigator 21, Ciudad Autonoma de Buenos Aires, Argentina; Not yet recruiting

Investigator 23, Ciudad Autonoma de Buenos Aires, Argentina; Not yet recruiting

Investigator 1, Cordoba, Argentina; Recruiting

Investigator 14, Cordoba, Argentina; Not yet recruiting

Investigator 15, Santa Fe, Argentina; Recruiting

Investigator 1, Sao Paulo, Brazil; Not yet recruiting

Investigator 3, Sao Paulo, Brazil; Not yet recruiting

Investigator 18, Sao Paulo, Brazil; Not yet recruiting

Investigator 1, Chillán, Chile; Not yet recruiting

Investigator 2, Santiago, Chile; Not yet recruiting

Investigator 3, Talcahuano, Chile; Not yet recruiting

Investigator4, Termuco, Chile; Recruiting

Investigator 5, Santiago, Chile; Recruiting

Investigator 6, Coquimbo, Chile; Recruiting

Investigator 7, Santiago, Chile; Not yet recruiting

Investigator 8, Santiago, Chile; Recruiting

Investigator 9, Santiago, Chile; Not yet recruiting

Investigator 10, Santiago, Chile; Not yet recruiting

Investigator 11, Santaigo, Chile; Recruiting

Investigator 12, Valparaiso, Chile; Recruiting

Investigator 1, Villejuif Cedex, France; Recruiting

Investigator 2, Nice Cedex 1, France; Recruiting

Investigator 3, Marseille Cedex 5, France; Recruiting

Investigator 5, Bayeux Cedex, France; Recruiting

Investigator 8, Saint-Etienne Cedex 2, France; Not yet recruiting

Investigator 9, Le Kremlin Bicetre Cedex, France; Recruiting

Investigator 10, Le Seyne Sur Mer, France; Not yet recruiting

Investigator 11, Nimes Cedex, France; Not yet recruiting

Investigator 14, Montpellier Cedex, France; Withdrawn

Investigator 6, Clermont-Fellamol, France; Recruiting

Investigator 15, Orleans- Cedex, France; Recruiting

Investigator 16, Talbes, France; Not yet recruiting

Investigator 17, Bayonnc, France; Not yet recruiting

Investigator 18, Bordeaux, France; Not yet recruiting

Investigator 19, Limoges, France; Not yet recruiting

Investigator 20, Toulouse, France; Not yet recruiting

Investigator 1, Daugavpils, Latvia; Recruiting

Investigator 2, Riga, Latvia; Recruiting

Investigator 1, Mexico DF, Mexico; Not yet recruiting

Investigator 2, Mexico DF, Mexico; Not yet recruiting

Investigator 3, Barranquitas, Guadalajara, Mexico; Not yet recruiting

Investigator 4, Mexico DF, Mexico; Not yet recruiting

Investigator 5, Zapopan, Mexico; Not yet recruiting

Investigator 6, Mérida, Mexico; Not yet recruiting

Investigator 7, Durango, Mexico; Not yet recruiting

Investigator 8, Mexico DF, Mexico; Not yet recruiting

Investigator 9, Aguascalientes, Mexico; Not yet recruiting

Investigator 11, Victoria, Mexico; Not yet recruiting

Investigator 12, Monterrey, Mexico; Not yet recruiting

Investigator 13, Mexico DF, Mexico; Not yet recruiting

Investigator 14, Chihuahua, Mexico; Not yet recruiting

Investigator 1, Lima, Peru; Not yet recruiting

Investigator 2, Lima, Peru; Not yet recruiting

Investigator 3, Lima, Peru; Not yet recruiting

Investigator 4, Lima, Peru; Not yet recruiting

Investigator 5, Lima, Peru; Not yet recruiting

Investigator 6, Lima, Peru; Not yet recruiting

Investigator 1, Kiev, Ukraine; Not yet recruiting

Investigator 2, Kharkiv, Ukraine; Not yet recruiting

Investigator 3, Kiev, Ukraine; Withdrawn

Investigator 4, Kiev, Ukraine; Withdrawn

Investigator 5, Kiev, Ukraine; Withdrawn

Investigator 6, Kiev, Ukraine; Not yet recruiting

Investigator 7, Kiev, Ukraine; Not yet recruiting

Investigator 8, Kharkiv, Ukraine; Recruiting

Investigator 9, Lviv, Ukraine; Not yet recruiting

Investigator 10, Poltava, Ukraine; Recruiting

Investigator 11, Donetsk, Ukraine; Recruiting

Investigator 12, Donetsk, Ukraine; Recruiting

Investigator 13, Kiev, Ukraine; Recruiting

Investigator 14, Kiev, Ukraine; Not yet recruiting

Investigator 15, Cherkasy, Ukraine; Recruiting

Investigator 20, Salvador, Bahia, Brazil; Not yet recruiting

Investigator 21, Salvador, Bahia, Brazil; Not yet recruiting

Investigator 2, Bernal, Buenos Aires, Argentina; Withdrawn

Investigator 3, La Plata, Buenos Aires, Argentina; Recruiting

Investigator 4, Caseros, Buenos Aires, Argentina; Withdrawn

Investigator 8, Villa Dominico, Buenos Aires, Argentina; Recruiting

Investigator 11, La Plata, Buenos Aires, Argentina; Not yet recruiting

Investigator 12, Pergamino, Buenos Aires, Argentina; Recruiting

Investigator 16, Mar del Plata, Buenos Aires, Argentina; Withdrawn

Investigator 20, San Isidro, Buenos Aires, Argentina; Not yet recruiting

Investigator 22, Quilmes, Buenos Aires, Argentina; Not yet recruiting

Investigator 8, Laguna Hills, California, United States; Withdrawn

Investigator 17, Loma Linda, California, United States; Withdrawn

Investigator 19, Santa Monica, California, United States; Withdrawn

Investigator 8, Fortaleza, Ceará, Brazil; Not yet recruiting

Investigator 9, New Haven, Connecticut, United States; Withdrawn

Investigator 13, St. Petersburg, Florida, United States; Terminated

Investigator 18, Orlando, Florida, United States; Withdrawn

Investigator 7, Goiania, Goiás, Brazil; Not yet recruiting

Investigator 2, Elkhart, Indiana, United States; Terminated

Investigator 11, Indianapolis, Indiana, United States; Withdrawn

Investigator 16, Indianapolis, Indiana, United States; Withdrawn

Investigator 1, Shreveport, Louisiana, United States; Terminated

Investigator 13, Belo Horizonte, Minas Gerais, Brazil; Not yet recruiting

Investigator 22, Belo Horizonte, Minas Gerais, Brazil; Not yet recruiting

Investigator 3, Glen Falls, New York, United States; Terminated

Investigator 7, Great Neck, New York, United States; Withdrawn

Investigator 10, Cedarhurst, New York, United States; Withdrawn

Investigator 4, Winston-Salem, North Carolina, United States; Terminated

Investigator 15, Canton, Ohio, United States; Terminated

Investigator 4, Curitiba, Parana, Brazil; Not yet recruiting

Investigator 15, Londrina, Paraná, Brazil; Not yet recruiting

Investigator 2, Porto Alegre, Rio Grande do Sul, Brazil; Not yet recruiting

Investigator 5, Pelotas, Rio Grande do Sul, Brazil; Not yet recruiting

Investigator 6, Ijui, Rio Grande do Sul, Brazil; Not yet recruiting

Investigator 11, Porto Alegre, Rio Grande do Sul, Brazil; Not yet recruiting

Investigator 12, Porto Alegre, Rio Grande do Sul, Brazil; Not yet recruiting

Investigator 19, Porto Alegre, Rio Grande do Sul, Brazil; Not yet recruiting

Investigator 14, Itajaí, Santa Catarina, Brazil; Not yet recruiting

Investigator 23, Florianópolis, Santa Catarina, Brazil; Not yet recruiting

Investigator 6, Rosario, Santa Fe, Argentina; Not yet recruiting

Investigator 10, Rosario, Santa Fe, Argentina; Recruiting

Investigator 13, Rosario, Santa Fe, Argentina; Recruiting

Investigator 9, Ribeirao Preto, Sao Paulo, Brazil; Not yet recruiting

Investigator 10, Campinas, Sao Paulo, Brazil; Not yet recruiting

Investigator 16, Barretos, Sao Paulo, Brazil; Not yet recruiting

Investigator 17, Santo André, Sao Paulo, Brazil; Not yet recruiting

Investigator 10, Hermosilo, Sonora, Mexico; Not yet recruiting

Investigator 5, Colleyville, Texas, United States; Withdrawn

Investigator 14, Houston, Texas, United States; Withdrawn

Investigator 5, San Miguel de Tucuman, Tucuman, Argentina; Recruiting

Investigator 6, Spokane, Washington, United States; Withdrawn

Starting date: June 2007
Ending date: April 2009
Last updated: October 7, 2008