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

This study has been terminated.
(Recall of rescue medication, alternative rescue medication availability issues.)
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT00505414
First received: July 19, 2007
Last updated: July 5, 2010
Last verified: July 2010
  Purpose

The purpose of this study is to determine whether CG5503 (tapentadol) is effective and safe in the treatment of chronic tumor related pain compared to placebo.


Condition Intervention Phase
Tumors
Pain
Drug: Tapentadol Extended Release (CG5503)
Drug: Morphine Sulphate Controlled Release
Drug: Matching Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Withdrawal, Active- and Placebo-controlled, Double-blind, Multi-center Phase III Trial Assessing Safety and Efficacy of Oral CG5503 (Tapentadol) Prolonged Release (PR*) in Subjects With Moderate to Severe Chronic Malignant Tumor-related Pain. *Prolonged Release and is the Recommended Nomenclature for Use in the European Union (EU). ER Means Extended Release and is the Recommended Nomenclature for Use in the United States of America (USA). "PR" is Synonymous With "ER" and is Interchangeable.

Resource links provided by NLM:


Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • Responder [ Time Frame: completed 28 days in the maintenance phase ] [ Designated as safety issue: No ]

    A "responder" is a participant in the study that:

    1. completed 28 days of the maintenance phase
    2. had a numeric rating scale score below 5 on the 11 point scale (where 0 indicates no pain and 10 indicates worst possible pain)
    3. did not use more than 30 mg of rescue medication per day on average in the 28 day maintenance period.

    A participant that met all 3 of the above-mentioned criteria is counted as a responder, in other words the participant benefited from the assigned drug treatment. A participant that fails to meet only 1 of the 3 criteria is not counted as a responder.



Secondary Outcome Measures:
  • Categorized Patient Global Impression of Change [ Time Frame: at day 15 - at the end of the titration phase ] [ Designated as safety issue: No ]
    The Patient Global Impression of Change (PGIC) is an instrument whereby the participants indicates the perceived change into one of 7 categories. Scores range from very much improved to very much worse.

  • Categorized Patient Global Impression of Change (PGIC) [ Time Frame: at day 43 - at the end of the maintenance phase ] [ Designated as safety issue: No ]
    The Patient Global Impression of Change (PGIC) is an instrument whereby the participants indicates the perceived change into one of 7 categories. Scores range from very much improved to very much worse.


Enrollment: 93
Study Start Date: June 2007
Study Completion Date: August 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Morphine Controlled Release
After signing informed consent eligible subjects were randomized (2:1) to receive either Tapentadol Extended Release or Morphine Controlled Release. The oral medication was taken twice daily, morning & evening every 12 hours (with a minimum of 6 hours between doses). Subjects randomized to the morphine arm remained on morphine once they entered the maintenance phase of the study.
Drug: Morphine Sulphate Controlled Release
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 the dose level established in titration phase.
Experimental: Tapentadol Extended Release (CG5503)
After signing informed consent eligible subjects were randomized (2:1) to receive either Tapentadol Extended Release or Morphine Controlled Release. Subjects randomized to Tapentadol in the titration phase were re-randomized (1:1) to receive either Tapentadol or matched placebo in the maintenance phase. The oral medication was taken twice daily, morning & evening every 12 hours (with a minimum of 6 hours between doses).
Drug: Tapentadol Extended Release (CG5503)
Titration phase: Starting at 100 mg Tapentadol twice daily, increasing as necessary up to a maximum of 250 mg Tapentadol twice daily. Re-randomization to continue on Tapentadol Extended Release or Matched Placebo in the Maintenance phase. Maintenance phase: continuing on the dose level established in titration phase.
Placebo Comparator: Matched placebo
After signing informed consent eligible subjects were randomized (2:1) to receive either Tapentadol Extended Release or Morphine Controlled Release. Subjects randomized to Tapentadol in the titration phase were re-randomized (1:1) to receive either Tapentadol or matching placebo in the maintenance phase. The oral medication was taken twice daily, morning & evening every 12 hours (with a minimum of 6 hours between doses).
Drug: Matching Placebo
At the end of the titration phase subjects on Tapentadol (CG5503) Extended Release were re-randomized to continue on either Tapentadol Extended Release or Matched Placebo in the Maintenance phase. Maintenance phase: continuing on the 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. Tapentadol, 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 Tapentadol Prolonged Release (ER) compared to a tablet with no active ingredient drug (placebo) and a 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 Controlled Release (CR) twice daily or 100 mg Tapentadol ER taken twice daily (bid). Based on effectiveness and side effects subjects can up-titrate in steps of 50 mg Tapentadol ER or 15 mg Morphine Sulfate CR to a maximal dose of 250 mg Tapentadol ER bid or 90 mg Morphine Sulfate CR twice daily respectively. If subjects meet the stabilization 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, defined as a responder include the pain intensity numeric rating scale (NRS). The Patient Global Impression of Change scale (PGIC) will also be used as a secondary efficacy endpoint. 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 tapentadol.

  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 at least 5 points on an 11-point Numeric Rating Scale (where 0 indicates no pain and 10 indicates worst possible pain).
  • Have an expected course of the disease such that 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 hypercalcemia
  • 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 hepatitis C, or Human Immunodeficiency Virus (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 37 Study Locations
Sponsors and Collaborators
Grünenthal GmbH
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Principal Investigator: P. Poulain, Dr. Gustave Roussy, Cancer Campus, Grand Paris
  More Information

No publications provided

Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT00505414     History of Changes
Other Study ID Numbers: 672519
Study First Received: July 19, 2007
Results First Received: May 27, 2010
Last Updated: July 5, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Grünenthal GmbH:
Opioid
Centrally acting analgesic
CG5503 IR
Tumor related pain
Cancer related pain
Morphine sulfate CR
Pain assessment
Placebo

Additional relevant MeSH terms:
Neoplasms
Morphine
Analgesics
Analgesics, Opioid
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014