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

NCT ID: NCT00505414

Last Updated: 2019-11-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2009-05-31

Brief Summary

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.

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, randomized-withdrawal, multicenter trial. To maintain the blind all subjects were re-randomized at the start of the maintenance period. To maintain the blind all tapentadol subjects were re-randomized at the start of the maintenance period. Subjects that received morphine in the titration period continued in the maintenance period on morphine.

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 participants 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.

Conditions

Pain; Neoplasm; Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Matching Placebo

Oral Tapentadol 100 mg to 250 mg twice daily. Followed by matching placebo in the maintenance (i.e. randomized withdrawal phase).

Group Type: PLACEBO_COMPARATOR

Matching Placebo in the Maintenance Phase after Tapentadol in the Titration Phase

Intervention Type: DRUG

Participant randomized to placebo in the maintenance phase received 100 mg tapentadol prolonged release twice daily for 3 days to taper them off of the tapentadol dose they had received in the titration period. From the fourth day of the maintenance period onwards they received placebo twice daily.

Morphine Controlled Release

Oral Morphine 45 mg to 90 mg twice daily.

Group Type: ACTIVE_COMPARATOR

Morphine in the Maintenance Phase

Intervention Type: DRUG

Participant started the trials with 45 mg morphine controlled release twice daily. Upward titration could then occur at a minimum of 3-day intervals in increments of 15 mg morphine twice daily. The maximum dose of morphine controlled release was 90 mg twice daily. Downward titration (but not below 45 mg twice daily) was permitted. In the maintenance phase participants continued on the dose level established in titration phase.

Participants randomized to the morphine arm remained on morphine if they qualified for the maintenance phase of the study. The participants were maintained on the dose established at the end of the titration phase. The adverse events listed were documented in the maintenance phase.

Morphine in the Titration Phase

Intervention Type: DRUG

After signing informed consent eligible subjects were randomized to receive morphine controlled release. The oral medication was taken twice daily, morning and evening every 12 hours (with a minimum of 6 hours between doses). Participant started the trials with 45 mg morphine controlled release twice daily. Upward titration could then occur at a minimum of 3-day intervals in increments of 15 mg morphine twice daily. The maximum dose of morphine controlled release was 90 mg twice daily. Downward titration (but not below 45 mg twice daily) was permitted.

Tapentadol Extended Release

Oral Tapentadol 100 mg to 250 mg twice daily.

Group Type: EXPERIMENTAL

Tapentadol in the Titration Phase

Intervention Type: DRUG

Tapentadol in the Maintenance Phase

Intervention Type: DRUG

The participants re-randomized to receive tapentadol prolonged release in the maintenance phase were maintained on the dose established in the titration phase.

Interventions

Tapentadol in the Titration Phase

Intervention Type: DRUG

Morphine in the Maintenance Phase

Participant started the trials with 45 mg morphine controlled release twice daily. Upward titration could then occur at a minimum of 3-day intervals in increments of 15 mg morphine twice daily. The maximum dose of morphine controlled release was 90 mg twice daily. Downward titration (but not below 45 mg twice daily) was permitted. In the maintenance phase participants continued on the dose level established in titration phase.

Participants randomized to the morphine arm remained on morphine if they qualified for the maintenance phase of the study. The participants were maintained on the dose established at the end of the titration phase. The adverse events listed were documented in the maintenance phase.

Intervention Type: DRUG

Matching Placebo in the Maintenance Phase after Tapentadol in the Titration Phase

Participant randomized to placebo in the maintenance phase received 100 mg tapentadol prolonged release twice daily for 3 days to taper them off of the tapentadol dose they had received in the titration period. From the fourth day of the maintenance period onwards they received placebo twice daily.

Intervention Type: DRUG

Tapentadol in the Maintenance Phase

The participants re-randomized to receive tapentadol prolonged release in the maintenance phase were maintained on the dose established in the titration phase.

Intervention Type: DRUG

Morphine in the Titration Phase

After signing informed consent eligible subjects were randomized to receive morphine controlled release. The oral medication was taken twice daily, morning and evening every 12 hours (with a minimum of 6 hours between doses). Participant started the trials with 45 mg morphine controlled release twice daily. Upward titration could then occur at a minimum of 3-day intervals in increments of 15 mg morphine twice daily. The maximum dose of morphine controlled release was 90 mg twice daily. Downward titration (but not below 45 mg twice daily) was permitted.

Intervention Type: DRUG

Other Intervention Names

Palexia; Nucynta; MS Contin overencapsulated for blinding

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: collaborator

Grünenthal GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

P. Poulain, Dr.

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

001013

St. Petersburg, Florida, United States

001002

Elkhart, Indiana, United States

001001

Shreveport, Louisiana, United States

001010

Cedarhurst, New York, United States

001003

Glens Falls, New York, United States

001004

Winston-Salem, North Carolina, United States

001015

Canton, Ohio, United States

054003

La Plata, Buenos Aires, Argentina

054012

Pergamino, Buenos Aires, Argentina

054022

Quilmes, Buenos Aires, Argentina

054008

Villa Domínico, Buenos Aires, Argentina

054010

Rosario, Santa Fe Province, Argentina

054013

Rosario, Santa Fe Province, Argentina

054005

San Miguel de Tucumán, Tucumán Province, Argentina

54009

Ciudad de Buenos Aires, , Argentina

054015

Santa Fe, , Argentina

056006

Coquimbo, , Chile

056011

Santiago, , Chile

056008

Santiago, , Chile

056005

Santiago, , Chile

056003

Talcahuano, , Chile

056004

Temuco, , Chile

056012

Valparaíso, , Chile

033002

Nice, , France

033015

Orléans, , France

033001

Villejuif, , France

371001

Daugavpils, , Latvia

371002

Riga, , Latvia

380015

Cherkasy, , Ukraine

380011

Donetsk, , Ukraine

380012

Donetsk, , Ukraine

380008

Kharkiv, , Ukraine

380002

Kharkiv, , Ukraine

380013

Kiev, , Ukraine

380001

Kiev, , Ukraine

380009

Lviv, , Ukraine

380010

Poltava, , Ukraine

Countries

United States; Argentina; Chile; France; Latvia; Ukraine

Other Identifiers

2007-001985-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KF5503/16

Identifier Type: OTHER

Identifier Source: secondary_id

672519

Identifier Type: -

Identifier Source: org_study_id