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

NCT00505414 | Terminated Phase 3 Results

• 3 other identifiers: 6725192007-001985-34KF5503/16
• Study Type: interventional
• Target: 136
• Locations: 6 countries
• Sites: 37

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.

Conditions

Pain; Neoplasm; Cancer

Keywords

Chronic Tumor Related Pain; Analgesic; Tapentadol Extended Release; Morphine Sulfate Controlled Release; Pain assessment; Placebo

Outcome Measures

Primary Outcomes (1)

• Responder Rates in Maintenance Period

  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. This twice daily current pain score was averaged over Day 18 to Day 43. 3. did not use more than 30 mg of rescue medication per day on average in the 28 day (excluding the first 3 days) maintenance period (from Day 18 to Day 43). 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 at least 1 of the 3 criteria is not counted as a responder.

  End of the 4 week Maintenance Phase (Day 43)

Secondary Outcomes (1)

• Patient Global Impression of Change (PGIC)

  Day 15 corresponds with PGIC at end of titration phase; Day 43 corresponds with PGIC at end of maintenance phase

Study Arms (3)

Matching Placebo

PLACEBO COMPARATOR

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

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

Morphine Controlled Release

ACTIVE COMPARATOR

Oral Morphine 45 mg to 90 mg twice daily.

Drug: Morphine in the Maintenance Phase; Drug: Morphine in the Titration Phase

Tapentadol Extended Release

EXPERIMENTAL

Oral Tapentadol 100 mg to 250 mg twice daily.

Drug: Tapentadol in the Titration Phase; Drug: Tapentadol in the Maintenance Phase

Interventions

Tapentadol in the Titration Phase DRUG

Also known as: Palexia, Nucynta

Tapentadol Extended Release

Morphine in the Maintenance Phase 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.

Also known as: MS Contin overencapsulated for blinding

Morphine Controlled Release

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

Matching Placebo

Tapentadol in the Maintenance Phase DRUG

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

Tapentadol Extended Release

Morphine in the Titration Phase 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.

Morphine Controlled Release

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grünenthal GmbH: lead
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: collaborator

Study Sites (37)

001013

St. Petersburg, Florida, 80918, United States

Location

001002

Elkhart, Indiana, 46514, United States

Location

001001

Shreveport, Louisiana, 71103, United States

Location

001010

Cedarhurst, New York, 11516, United States

Location

001003

Glens Falls, New York, 12801, United States

Location

001004

Winston-Salem, North Carolina, 27103, United States

Location

001015

Canton, Ohio, 44718, United States

Location

054003

La Plata, Buenos Aires, B1900BAJ, Argentina

Location

054012

Pergamino, Buenos Aires, B2700CPM, Argentina

Location

054022

Quilmes, Buenos Aires, B1878AAT, Argentina

Location

054008

Villa Domínico, Buenos Aires, B1874ACL, Argentina

Location

054010

Rosario, Santa Fe Province, S2000CVD, Argentina

Location

054013

Rosario, Santa Fe Province, S2000CVD, Argentina

Location

054005

San Miguel de Tucumán, Tucumán Province, T4000IAK, Argentina

Location

54009

Ciudad de Buenos Aires, C1185AAT, Argentina

Location

054015

Santa Fe, S3000FFU, Argentina

Location

056006

Coquimbo, Chile

Location

056011

Santiago, 7510009, Chile

Location

056008

Santiago, 8380000, Chile

Location

056005

Santiago, Chile

Location

056003

Talcahuano, Chile

Location

056004

Temuco, Chile

Location

056012

Valparaíso, 236-3058, Chile

Location

033002

Nice, 06002, France

Location

033015

Orléans, 45032, France

Location

033001

Villejuif, 94805, France

Location

371001

Daugavpils, 5420, Latvia

Location

371002

Riga, 1079, Latvia

Location

380015

Cherkasy, 18009, Ukraine

Location

380011

Donetsk, 83092, Ukraine

Location

380012

Donetsk, 83092, Ukraine

Location

380008

Kharkiv, 61024, Ukraine

Location

380002

Kharkiv, 61070, Ukraine

Location

380013

Kiev, 01601, Ukraine

Location

380001

Kiev, 61070, Ukraine

Location

380009

Lviv, 79031, Ukraine

Location

380010

Poltava, 36011, Ukraine

Location

MeSH Terms

Conditions

Pain; Neoplasms

Interventions

Tapentadol; Morphine; Masks

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Surgical Attire; Equipment and Supplies, Hospital; Equipment and Supplies; Protective Devices; Personal Protective Equipment; Surgical Equipment; Manufactured Materials; Technology, Industry, and Agriculture

Limitations and Caveats

Early termination, due to a recall of the morphine rescue medication and issues regarding supply of an alternative, lead to only 93 participants out of the 573 planned (16%) being available for analysis. The data should be interpreted with caution.

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Grünenthal GmbH

Clinical-Trials@grunenthal.com

+49 (0)241 569 3223

Study Officials

• P. Poulain, Dr.

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2007
• First Posted: July 23, 2007
• Study Start: June 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: May 1, 2009
• Last Updated: November 1, 2019
• Results First Posted: July 2, 2010

Record last verified: 2019-10

Locations

FR (3); LA (2); US (7); AR (9); UA (9); CL (7)