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

NCT ID: NCT00472303

Last Updated: 2019-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 622 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2012-06-30

Brief Summary

The purpose of this study will be to determine whether tapentadol (CG5503) is effective and safe in the treatment of chronic tumor related pain compared to placebo. In addition tapentadol (CG5503) will also be compared to morphine controlled release, also referred to as slow release (SR).

*Tapentadol prolonged-release (PR) is the term used in the European Union and is referred to as extended release (ER) in the United States.

Detailed Description

Normally chronic tumor related pain is controlled when participants 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 (CG5503), a newly synthesized drug with an prolonged release (PR) formulation, also acts as a centrally acting pain reliever but has 2 mechanisms of action. The aim of this trial is to investigate the effectiveness (level of pain control) and safety (side effects) of tapentadol (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, randomized withdrawal design, multicenter trial.

The trial includes a 2 week titration phase starting with either 40 mg morphine (PR) bid (bid = twice daily dosing, one dose in the morning and one dose in the evening) or 100 mg tapentadol (CG5503) PR bid. Based on effectiveness and side effects subjects can up-titrate in steps of 50 mg tapentadol (CG5503 PR) to a maximal dose of 250 mg tapentadol (CG5503) PR bid or 100 mg morphine PR bid. If participants 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. Only participants on tapentadol in the titration phase will be re-randomized to either matching placebo or to tapentadol. To maintain the blinding nature of the trial participants in the morphine arm during the titration phase will also be re-randomized however they will all remain on morphine controlled release in the maintenance phase. Placebo to match tapentadol tablets, as well as placebo to match morphine capsules, will be used to mask the treatment allocation.

Participants will be issued with an electronic diary (eDiary) to capture Numeric Rating Scale (NRS) pain intensities.

Assessments of pain relief include the pain intensity numeric rating scale (NRS) and patient global impression of change (PGIC). Safety evaluations include monitoring of adverse events, physical examinations, clinical laboratory tests and electrocardiograms. Venous blood samples will be collected for the determination of serum concentrations of tapentadol (CG5503).

Conditions

Tumor; Pain

Study Design

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

Study Groups

Matching Placebo after Tapentadol in Titration Phase

Oral Tapentadol 100 mg to 250 mg twice daily. Participants randomized to placebo in the maintenance phase received 100 mg tapentadol prolonged release twice daily for 3 days to taper them off the tapentadol dose they had received in the Titration Phase. From the 4th day (Day 18) all participants received matching placebo in the maintenance (i.e. randomized withdrawal) phase.

Group Type: PLACEBO_COMPARATOR

Tapentadol Extended Release

Intervention Type: DRUG

Tablet taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses. Titration phase: Starting at 100 mg, increasing at a minimum of 3 day intervals by 50 mg, with a maximum dose of 250 mg.

Matching Placebo after Tapentadol in the Titration Phase.

Intervention Type: DRUG

Tablet taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses. In the maintenance phase only to participants that were randomized to tapentadol in the titration phase.

Morphine Controlled Release

Oral Morphine 40 mg to 100 mg twice daily. Capsule taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses. Maintenance phase: continuing on dose level established in titration phase.

Group Type: ACTIVE_COMPARATOR

Morphine Sulphate Controlled Release

Intervention Type: DRUG

Capsule taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses. Titration phase: Starting at 40 mg, increasing at a minimum of 3 days intervals by 20 mg, with a maximum dose of 100 mg. Maintenance phase: continuing on dose level established in titration phase.

Tapentadol Prolonged Release

Oral Tapentadol 100 mg to 250 mg twice daily. Tablet taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses.

Group Type: EXPERIMENTAL

Tapentadol Extended Release

Intervention Type: DRUG

Tablet taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses. Titration phase: Starting at 100 mg, increasing at a minimum of 3 day intervals by 50 mg, with a maximum dose of 250 mg.

Interventions

Tapentadol Extended Release

Tablet taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses. Titration phase: Starting at 100 mg, increasing at a minimum of 3 day intervals by 50 mg, with a maximum dose of 250 mg.

Intervention Type: DRUG

Matching Placebo after Tapentadol in the Titration Phase.

Tablet taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses. In the maintenance phase only to participants that were randomized to tapentadol in the titration phase.

Intervention Type: DRUG

Morphine Sulphate Controlled Release

Capsule taken orally, twice daily, morning \& evening with preferably 12 hours (not less than 6 hours) between doses. Titration phase: Starting at 40 mg, increasing at a minimum of 3 days intervals by 20 mg, with a maximum dose of 100 mg. Maintenance phase: continuing on dose level established in titration phase.

Intervention Type: DRUG

Other Intervention Names

Palexia; Nucynta; Yantil; MST® CONTINUS®

Eligibility 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.
• Expected course of the disease and the pain that would permit compliance with the trial protocol over the entire trial period.

Exclusion Criteria

• Subjects will be excluded from the study if they have a history of seizure disorder or epilepsy;
• known history and/or presence of cerebral tumor or 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,
• inadequate bone marrow reserve
• 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.

• 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

Hans Georg Kress, Dr.

Role: PRINCIPAL_INVESTIGATOR

Clinic of Anaesthesiology and Pain Management, AKH Vienna

Locations

Site 043004

Klagenfurt, , Austria

Site 043002

Vienna, , Austria

Site 043001

Vienna, , Austria

Site 043005

Vienna, , Austria

Site 359013

Gabrovo, , Bulgaria

Site 359011

Pleven, , Bulgaria

Site 359014

Plovdiv, , Bulgaria

Site 359004

Shumen, , Bulgaria

Site 359008

Sofia, , Bulgaria

Site 359012

Varna, , Bulgaria

Site 385007

Osijek, , Croatia

Site 385001

Slavonski Brod, , Croatia

Site 385004

Varaždin, , Croatia

Site 385006

Zabok, , Croatia

Site 385002

Zagreb, , Croatia

Site 385003

Zagreb, , Croatia

Site 420005

Brno, , Czechia

Site 420002

České Budějovice, , Czechia

Site 420006

Hradec Králové, , Czechia

Site 420007

Liberec, , Czechia

Site 420008

Olomouc, , Czechia

Site 420001

Pilsen, , Czechia

Site 420004

Prague, , Czechia

Site 033101

Tarbes, , France

Site 049009

Berlin, , Germany

Site 049012

Cologne, , Germany

Site 049014

Essen, , Germany

Site 049007

Löwenstein, , Germany

Site 049020

Potsdam, , Germany

Site 049006

Waldkirch, , Germany

Site 049002

Wiesbaden, , Germany

Site 036001

Debrecen, , Hungary

Site 036005

Komárom, , Hungary

Site 036003

Mátraháza, , Hungary

Site 036002

Nyíregyháza, , Hungary

Site 036010

Szekszárd, , Hungary

Site 036006

Székesfehérvár, , Hungary

Site 036009

Székesfehérvár, , Hungary

Site 039001

Napoli, , Italy

Site 373001

Chisinau, , Moldova

Site 373002

Chisinau, , Moldova

Site 048004

Bydgoszcz, , Poland

Site 048005

Gdansk, , Poland

Site 048007

Poznan, , Poland

Site 048001

Warsaw, , Poland

Site 040006

Brasov, , Romania

Site 040002

Bucharest, , Romania

Site 040003

Bucharest, , Romania

Site 040004

Bucharest, , Romania

Site 040005

Cluj-Napoca, , Romania

Site 040001

Iași, , Romania

Site 040007

Timișoara, , Romania

Site 007010

Arkhangelsk, , Russia

Site 007003

Moscow, , Russia

Site 007007

Nizhny Novgorod, , Russia

Site 007012

Vladikavkaz, , Russia

Site 007005

Yaroslavl, , Russia

Site 381003

Belgrade, , Serbia

Site 381004

Belgrade, , Serbia

Site 381005

Belgrade, , Serbia

Site 381001

Kamenitz, , Serbia

Site 381002

Niš, , Serbia

Site 421005

Banská Bystrica, , Slovakia

Site 421001

Košice, , Slovakia

Site 034009

Barcelona, , Spain

Site 034005

Barcelona, , Spain

Site 034006

Mahon, , Spain

Site 034012

Pamplona, , Spain

Site 034004

Seville, , Spain

Site 034002

Valencia, , Spain

Site 046001

Stockholm, , Sweden

Countries

Austria; Bulgaria; Croatia; Czechia; France; Germany; Hungary; Italy; Moldova; Poland; Romania; Russia; Serbia; Slovakia; Spain; Sweden

References

Kress HG, Koch ED, Kosturski H, Steup A, Karcher K, Lange B, Dogan C, Etropolski MS, Eerdekens M. Tapentadol prolonged release for managing moderate to severe, chronic malignant tumor-related pain. Pain Physician. 2014 Jul-Aug;17(4):329-43.

Reference Type: RESULT

PMID: 25054392 (View on PubMed)

Kress HG, Koch ED, Kosturski H, Steup A, Karcher K, Dogan C, Etropolski M, Eerdekens M. Direct conversion from tramadol to tapentadol prolonged release for moderate to severe, chronic malignant tumour-related pain. Eur J Pain. 2016 Oct;20(9):1513-8. doi: 10.1002/ejp.875. Epub 2016 Apr 7.

Reference Type: RESULT

PMID: 27062079 (View on PubMed)

Other Identifiers

2006-004997-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KF5503/15

Identifier Type: OTHER

Identifier Source: secondary_id

761101

Identifier Type: -

Identifier Source: org_study_id