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

NCT00472303 | Completed Phase 3 Results

• 3 other identifiers: 7611012006-004997-28KF5503/15
• Study Type: interventional
• Target: 622
• Locations: 15 countries
• Sites: 66

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.

Conditions

Tumor; Pain

Keywords

Opioid; Central acting analgesic; CG5503 PR; Tumor related pain; Cancer related pain; Morphine; Pain assessment; Placebo

Outcome Measures

Primary Outcomes (1)

• Number of Participants Scored as Responder in Maintenance Phase.

  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 20 mg of rescue medication per day on average in the 28 day 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 failed to meet only 1 of the 3 criteria is not counted as a responder.

  Day 18 through Day 43 (End of Maintenance Phase)

Secondary Outcomes (22)

• Average Daily Pain Intensity Scores, Averaged Per Week by Treatment, During the Titration Phase in the Tapentadol Treatment Arm.

  Day 1 through Day 14 (End of Titration Phase)

• Average Daily Pain Intensity Scores, Averaged Per Week by Treatment, During the Titration Phase in the Morphine Treatment Arm.

  Day 1 through Day 14 (End of Titration Phase)

• Average Daily Pain Intensity Scores, Averaged Per Week by Treatment, During the Maintenance Phase.

  Day 18 through Day 43 (End of Maintenance Phase)

• Current Pain Intensity Scores, Averaged Per Week, During the Titration Phase in the Tapentadol Arm.

  Day 1 through Day 14 (End of Titration Phase)

• Current Pain Intensity Scores, Averaged Per Week, During the Titration Phase in the Morphine Arm.

  Day 1 through Day 14 (End of Titration Phase)

Study Arms (3)

Matching Placebo after Tapentadol in Titration Phase

PLACEBO COMPARATOR

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.

Drug: Tapentadol Extended Release; Drug: Matching Placebo after Tapentadol in the Titration Phase.

Morphine Controlled Release

ACTIVE COMPARATOR

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.

Drug: Morphine Sulphate Controlled Release

Tapentadol Prolonged Release

EXPERIMENTAL

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.

Drug: Tapentadol Extended Release

Interventions

Tapentadol Extended Release 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.

Also known as: Palexia, Nucynta, Yantil

Matching Placebo after Tapentadol in Titration Phase; Tapentadol Prolonged Release

Matching Placebo after Tapentadol in the Titration Phase. 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.

Matching Placebo after Tapentadol in Titration Phase

Morphine Sulphate Controlled Release 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.

Also known as: MST® CONTINUS®

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:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (71)

Site 043004

Klagenfurt, 9020, Austria

Location

Site 043002

Vienna, 1020, Austria

Location

Site 043001

Vienna, 1090, Austria

Location

Site 043005

Vienna, 1100, Austria

Location

Site 359013

Gabrovo, 5300, Bulgaria

Location

Site 359011

Pleven, 5800, Bulgaria

Location

Site 359014

Plovdiv, 4004, Bulgaria

Location

Site 359004

Shumen, 9700, Bulgaria

Location

Site 359008

Sofia, 1784, Bulgaria

Location

Site 359012

Varna, 9003, Bulgaria

Location

Site 385007

Osijek, 31000, Croatia

Location

Site 385001

Slavonski Brod, 35000, Croatia

Location

Site 385004

Varaždin, 42000, Croatia

Location

Site 385006

Zabok, 49210, Croatia

Location

Site 385002

Zagreb, 10000, Croatia

Location

Site 385003

Zagreb, 10000, Croatia

Location

Site 420005

Brno, 62500, Czechia

Location

Site 420002

České Budějovice, 37087, Czechia

Location

Site 420006

Hradec Králové, 50005, Czechia

Location

Site 420007

Liberec, 46063, Czechia

Location

Site 420008

Olomouc, 77520, Czechia

Location

Site 420001

Pilsen, 30460, Czechia

Location

Site 420004

Prague, 18181, Czechia

Location

Site 033101

Tarbes, 65000, France

Location

Site 049009

Berlin, 12627, Germany

Location

Site 049012

Cologne, 50996, Germany

Location

Site 049014

Essen, 45122, Germany

Location

Site 049007

Löwenstein, 74245, Germany

Location

Site 049020

Potsdam, 14467, Germany

Location

Site 049006

Waldkirch, 79183, Germany

Location

Site 049002

Wiesbaden, 65185, Germany

Location

Site 036001

Debrecen, 4043, Hungary

Location

Site 036005

Komárom, 2900, Hungary

Location

Site 036003

Mátraháza, 3233, Hungary

Location

Site 036002

Nyíregyháza, 4412, Hungary

Location

Site 036010

Szekszárd, 7100, Hungary

Location

Site 036006

Székesfehérvár, 8000, Hungary

Location

Site 036009

Székesfehérvár, 8000, Hungary

Location

Site 039001

Napoli, 80131, Italy

Location

Site 373001

Chisinau, 2025, Moldova

Location

Site 373002

Chisinau, 2025, Moldova

Location

Site 048004

Bydgoszcz, 85796, Poland

Location

Site 048005

Gdansk, 80286, Poland

Location

Site 048007

Poznan, 60355, Poland

Location

Site 048001

Warsaw, 02781, Poland

Location

Site 040006

Brasov, 500074, Romania

Location

Site 040002

Bucharest, 022328, Romania

Location

Site 040003

Bucharest, 022328, Romania

Location

Site 040004

Bucharest, 022328, Romania

Location

Site 040005

Cluj-Napoca, 400015, Romania

Location

Site 040001

Iași, 700106, Romania

Location

Site 040007

Timișoara, 300239, Romania

Location

Site 007010

Arkhangelsk, 163045, Russia

Location

Site 007003

Moscow, 125284, Russia

Location

Site 007007

Nizhny Novgorod, 603140, Russia

Location

Site 007012

Vladikavkaz, 362007, Russia

Location

Site 007005

Yaroslavl, 150054, Russia

Location

Site 381003

Belgrade, 11000, Serbia

Location

Site 381004

Belgrade, 11000, Serbia

Location

Site 381005

Belgrade, 11000, Serbia

Location

Site 381001

Kamenitz, 21204, Serbia

Location

Site 381002

Niš, 18000, Serbia

Location

Site 421005

Banská Bystrica, 97517, Slovakia

Location

Site 421001

Košice, 04191, Slovakia

Location

Site 034009

Barcelona, 08208, Spain

Location

Site 034005

Barcelona, 08221, Spain

Location

Site 034006

Maó, 07703, Spain

Location

Site 034012

Pamplona, 31008, Spain

Location

Site 034004

Seville, 1013, Spain

Location

Site 034002

Valencia, 46014, Spain

Location

Site 046001

Stockholm, 17176, Sweden

Location

Related Publications (2)

• 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.

  PMID: 25054392 RESULT

• 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.

  PMID: 27062079 RESULT

MeSH Terms

Conditions

Neoplasms; Pain; Cancer Pain

Interventions

Tapentadol

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

Results Point of Contact

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

Clinical-Trials@grunenthal.com

+49 241 569 3223

Study Officials

• Hans Georg Kress, Dr.

  Clinic of Anaesthesiology and Pain Management, AKH Vienna

  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: May 10, 2007
• First Posted: May 11, 2007
• Study Start: July 1, 2007
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: November 4, 2019
• Results First Posted: May 7, 2014

Record last verified: 2019-10

Locations

SE (1); FR (1); CR (6); MO (2); CZ (7); IT (1); DE (7); AU (4); SL (2); RO (7); HU (7); PL (4); BU (6); ES (6); RU (5)