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

Condition(s) targeted: Tumor; 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):
Hans Georg Kress, Dr., Principal Investigator, Affiliation: Clinic of Anaesthesiology and Pain Management, AKH Vienna

Overall contact:
Claudia Leinweber, Phone: +49 (0)241-569, Ext: 2509, 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 SR.

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

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

Primary outcome: 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

Secondary outcome: 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

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

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

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.

Claudia Leinweber, Phone: +49 (0)241-569, Ext: 2509, Email: Clinical-Trials@grunenthal.com

Investigator 1, Vienna, Austria; Recruiting

Investigator 2, Vienna, Austria; Recruiting

Investigator 4, Klagenfurt, Austria; Recruiting

Investigator 5, Vienna, Austria; Not yet recruiting

Investigator 7, Oberpullendorf, Austria; Recruiting

Investigator 1, Veliko Turnovo, Bulgaria; Not yet recruiting

Investigator 3, Varna, Bulgaria; Not yet recruiting

Investigator 4, Shumen, Bulgaria; Recruiting

Investigator 5, Plovdiv, Bulgaria; Not yet recruiting

Investigator 6, Sofia, Bulgaria; Not yet recruiting

Investigator 1, Slavonski Brod, Croatia; Recruiting

Investigator 2, Zagreb, Croatia; Not yet recruiting

Investigator 3, Zagreb, Croatia; Recruiting

Investigator 4, Varazdin, Croatia; Recruiting

Investigator 5, Rijeka, Croatia; Not yet recruiting

Investigator 1, Pilsen, Czech Republic; Recruiting

Investigator 2, Ceske Budejovice, Czech Republic; Not yet recruiting

Investigator 3, Prague, Czech Republic; Not yet recruiting

Investigator 4, Prague, Czech Republic; Not yet recruiting

Investigator 1, Hamburg, Germany; Terminated

Investigator 10, Frankfurt, Germany; Terminated

Investigator 2, Wiesbaden, Germany; Recruiting

Investigator 3, Herrsching, Germany; Terminated

Investigator 4, Freiburg, Germany; Not yet recruiting

Investigator 5, Hildesheim, Germany; Terminated

Investigator 6, Waldkirch, Germany; Terminated

Investigator 7, Ludwigsburg, Germany; Recruiting

Investigator 8, Berlin, Germany; Not yet recruiting

Investigator 9, Berlin, Germany; Recruiting

Investigator 12, Köln, Germany; Recruiting

Investigator 14, Essen, Germany; Not yet recruiting

Investigator 1, Debrecen, Hungary; Recruiting

Investigator 2, Nyiregyhaza, Hungary; Recruiting

Investigator 3, Mátraháza, Hungary; Recruiting

Investigator 4, Zalaegerszeg, Hungary; Not yet recruiting

Investigator 5, Komárom, Hungary; Recruiting

Investigator 6, Székesfehérvár, Hungary; Not yet recruiting

Investigator 1, Napoli, Italy; Recruiting

Investigator 2, Modena, Italy; Not yet recruiting

Investigator 4, Milano, Italy; Terminated

Investigator 1, Warszawa, Poland; Recruiting

Investigator 2, Poznan, Poland; Not yet recruiting

Investigator 3, Szczecin, Poland; Not yet recruiting

Investigator 5, Gdanks, Poland; Recruiting

Investigator 6, Gdansk, Poland; Not yet recruiting

Investigator 7, Poznan, Poland; Recruiting

Investigator 8, Bielsko-Biala, Poland; Not yet recruiting

Investigator 4, Bydgoszcz, Poland; Recruiting

Investigator 1, Iasi, Romania; Recruiting

Investigator 2, Bucharest, Romania; Recruiting

Site 3, Bucharest, Romania; Recruiting

Site 4, Bucharest, Romania; Recruiting

Investigator 5, Cluj-Napoca, Romania; Recruiting

Investigator 1, Moscow, Russian Federation; Not yet recruiting

Investigator 2, Moscow, Russian Federation; Not yet recruiting

Investigator 3, Moscow, Russian Federation; Not yet recruiting

Investigator 4, Smolensk, Russian Federation; Not yet recruiting

Investigator 5, Yaroslavl, Russian Federation; Recruiting

Investigator 6, Moscow, Russian Federation; Not yet recruiting

Investigator 7, Nizhniy Novgorod, Russian Federation; Recruiting

Investigator 1, Sremska Kamenica, Serbia; Recruiting

Investigator 2, Nis, Serbia; Recruiting

Investigator 3, Belgrade, Serbia; Recruiting

Investigator 4, Belgrade, Serbia; Recruiting

Investigator 1, Kosice, Slovakia; Recruiting

Investigator 4, Zilina, Slovakia; Terminated

Investigator 5, Banska Bystrica, Slovakia; Recruiting

Investigator 1, Barcelona, Spain; Recruiting

Investigator 2, Valencia, Spain; Recruiting

Investigator 3, Madrid, Spain; Recruiting

Investigator 4, Sevilla, Spain; Recruiting

Investigator 5, Barcelona, Spain; Recruiting

Investigator 6, Mahon Menorca, Spain; Recruiting

Investigator 7, Palma de Mallorca, Spain; Not yet recruiting

Investigator 8, Barcelona, Spain; Not yet recruiting

Investigator 9, Sabadell Barcelona, Spain; Not yet recruiting

Investigator 1, Bruderholz, Switzerland; Not yet recruiting

Investigator 2, Zürich, Switzerland; Not yet recruiting

Starting date: July 2007
Ending date: July 2008
Last updated: July 18, 2008