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

Sponsors and Collaborators:	Grünenthal GmbH Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:	Grünenthal GmbH
ClinicalTrials.gov Identifier:	NCT00505414

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.

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

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.

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.

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Tapentadol

U.S. FDA Resources

Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:

• 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 [ Time Frame: End of trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

•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 ( [ Time Frame: End of trial ] [ Designated as safety issue: No ]

Estimated Enrollment:	573
Study Start Date:	June 2007
Estimated Study Completion Date:	August 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Entering the titration phase subjects will be randomised 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 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 45 mg, increasing at a minimum of 3 day intervals by 15 mg, with a maximum dose of 90 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 (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

Eligibility

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

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00505414

Show 129 Study Locations

Sponsors and Collaborators

Grünenthal GmbH

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

Investigators

Principal Investigator:

P. Poulain, Dr.

Institut Gustave Roussy

More Information

No publications provided

Responsible Party:	Grünenthal GmbH ( Grünenthal GmbH )
Study ID Numbers:	672519
Study First Received:	July 19, 2007
Last Updated:	July 14, 2009
ClinicalTrials.gov Identifier:	NCT00505414 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Grünenthal GmbH:

Opiod
Centrally acting analgesic
CG5503 IR
Tumor related pain

Cancer related pain
Morphine sulfate CR
Pain assessment
Placebo

Study placed in the following topic categories:

Morphine
Central Nervous System Depressants
Narcotics
Pain

Peripheral Nervous System Agents
Analgesics
Analgesics, Opioid

Additional relevant MeSH terms:

Morphine
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 September 11, 2009