Tapentadol Prolonged Release (PR) Versus Oxycodone/Naloxone Prolonged Release in Severe Chronic Low Back Pain With a Neuropathic Component.

NCT01838616 | Completed Phase 4 Results

• 2 other identifiers: KF5503/602012-002943-11
• Study Type: interventional
• Target: 367
• Locations: 4 countries
• Sites: 50

Brief Summary

This was a clinical effectiveness trial designed to compare the effectiveness, safety, and tolerability of treatment with tapentadol prolonged release with that of oxycodone/naloxone prolonged release in non-opioid pre-treated subjects with severe chronic low back pain with a neuropathic pain component. Both tapentadol and the opioid oxycodone are effective in chronic severe pain and tapentadol and oxycodone/naloxone have shown advantages in gastrointestinal tolerability versus oxycodone. Therefore, it was of high scientific interest to compare the latter 2 analgesics with respect to gastrointestinal tolerability. Tapentadol may have advantages regarding the neuropathic pain-related symptoms of low back pain due to its 2 mechanisms of action.

Conditions

Back Pain; Low Back Pain; Neuropathic Pain

Keywords

Severe chronic low back pain; Neuropathic pain; Constipation

Outcome Measures

Primary Outcomes (2)

• Change in the Average Pain Intensity Score on an 11-point Numeric Rating Scale (NRS-3)

  For this pain assessment, the participant indicated the level of average pain experienced over the previous 3 days on an 11-point Numeric Rating Scale (NRS-3) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The value reported represents the change from the randomization visit (i.e., the last 3 days in the washout period prior to Investigational Medicinal Product initiation and titration) to the end of the continuation period (i.e., up to 9 weeks on the stable dose). The theoretical values range from -10 to 10. A negative sign indicates a decrease in pain from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (Baseline Visit).

  Baseline (Randomization Visit); End of Continuation Period (Week 12)

• Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) Total Score

  The Constipation Assessment (PAC-SYM) is a 12-item self-report questionnaire that assessed the severity of symptoms of constipation. Participants were asked "How severe have each of these symptoms been in the last two weeks?" e.g. "Pain in your stomach". There are 3 subscales: 4 questions on abdominal symptoms, 3 on rectal symptoms and 5 on stool symptoms. Responses were rated on a 5-point Likert scale ranging from 0 (absence of symptom) to 4 (very severe symptoms). If the changes in the overall or subscale scores are positive then there is a worsening in symptoms associated with constipation. The change in the assessment of constipation symptoms (PAC-SYM) total score from the Randomization Visit to the Final Evaluation Visit. The PAC-SYM overall score is the sum of scores of all non-missing items divided by the number of non-missing items (if at least 6 items were non-missing).

  Baseline (Randomization Visit); End of Continuation Period (Week 12)

Secondary Outcomes (29)

• Recalled Average Pain Intensity

  Baseline (Randomization Visit); End of Continuation Period (Week 12)

• Change in Recalled Average Pain Intensity at the End of Treatment

  Baseline (Randomization Visit); End of Continuation Period (Week 12)

• Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg

  Baseline (Randomization Visit); End of Continuation Period (Week 12)

• Change of Average Pain Intensity Over Three Days for Pain Radiating Towards or Into the Leg at the End of Treatment

  Baseline (Randomization Visit); End of Continuation Period (Week 12)

• Worst Pain Intensity Over the Past 24 Hours

  Baseline (Randomization Visit); End of Continuation Period (Week 12)

Study Arms (2)

Tapentadol Prolonged Release (PR)

EXPERIMENTAL

Drug: Tapentadol Prolonged Release

Oxycodone/Naloxone Prolonged Release

ACTIVE COMPARATOR

Drug: Oxycodone/Naloxone Prolonged Release

Interventions

Tapentadol Prolonged Release DRUG

All participants started with 50 mg tapentadol hydrochloride prolonged release (twice daily). The dose of tapentadol hydrochloride prolonged release will be adjusted in increments of 50 mg to a level that provided adequate analgesia. Titration will be after a minimum of 3 days on a dose. Participants are permitted a maximum dose of 250 mg twice a day (500 mg total daily dose). After titration participants will remain on the stable dose for 9 weeks.

Also known as: Nucynta, Palexia

Tapentadol Prolonged Release (PR)

Oxycodone/Naloxone Prolonged Release DRUG

All participants start with 10 mg/5 mg oxycodone/naloxone (twice daily). The dose of oxycodone/naloxone may be adjusted in increments of 10mg/ 5 mg oxycodone/naloxone to a level that provide adequate analgesia. Titration will be after a minimum of 3 days on a dose. Participants will be permitted a maximum dose of 50 mg/ 20 mg oxycodone/naloxone twice daily a day (100 mg/40 mg total daily dose). After titration participants will remain on the stable dose for 9 weeks.

Also known as: Targin

Oxycodone/Naloxone Prolonged Release

Eligibility Criteria

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

You may qualify if:

• Informed consent signed.
• Male or female 18 years of age or older.
• Women of childbearing potential must have a negative pregnancy test at the Enrollment Visit.
• Women of childbearing potential must practice medically acceptable methods of birth control during the trial.
• Participant must be appropriately communicative and able to differentiate with regard to location and intensity of the pain, and to complete the questionnaires used in this trial.
• Participants must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months prior to enrollment.
• Participant's pain must require a strong analgesic (defined as World Health Organization Step III) as judged by the investigator.
• Participants who require a washout of co-analgesics at enrolment must have an average pain score (NRS-3) of 5 points or higher. Participants who do not require a washout of co-analgesics at enrollment must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher.
• The painDETECT diagnostic screening questionnaire must be either "positive" (score of 19 to 38 inclusive) or "unclear" (score of 13 to 18 inclusive). If the participant is being treated with a stable regimen of centrally acting co-analgesics, a "negative" painDETECT score (score 9 points or higher).
• Participants must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher.
• Participants must score either "positive" (score of 19 to 38 inclusive) or "unclear" (score of 13 to 18 inclusive) on the painDETECT diagnostic screening questionnaire.

You may not qualify if:

• Presence of a clinically significant disease or clinical laboratory values that in the investigator's opinion may affect effectiveness, quality of life, or safety/tolerability assessments.
• Presence of active systemic or local infections that may, in the opinion of the investigator, affect the effectiveness, quality of life, or safety/tolerability assessments.
• Employees of the investigator or trial site, with direct involvement in this trial or other trials under the direction of the investigator or trial site, as well as family members of employees of the investigator.
• Participation in another trial concurrently, or within 4 weeks prior to the Enrollment Visit.
• Known to or suspected of not being able to comply with the protocol and/or appropriate use of the Investigational Medicinal Products.
• Any painful procedures (e.g., major surgery) scheduled during the trial duration (Enrollment Visit until Final Evaluation Visit) that may, in the opinion of the investigator, affect the effectiveness, quality of life, or safety assessments.
• Pending litigation or application for insurance/governmental benefits due to chronic pain or disability and/or if the granted benefits might be influenced by a successful participation in the trial.
• Low back pain caused by cancer and/or metastatic diseases.
• History of alcohol or drug abuse, or suspicion thereof in the investigator's judgment.
• Presence of concomitant autoimmune inflammatory conditions.
• Participants with acute intoxication with alcohol, hypnotics, centrally acting analgesics, or psychotropic active substances.
• Participants with severe renal impairment, i.e., estimated glomerular filtration rate less than 30 mL/min (according to the National Kidney Foundation 2002).
• Known history of clinical laboratory values or current clinical laboratory values reflecting moderately or severely impaired hepatic function.
• History of seizure disorder or epilepsy.
• Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm (including brain metastases if present at the Enrollment Visit). Severe traumatic brain injury within 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or post traumatic amnesia lasting more than 24 hours) or residual sequelae suggesting transient changes in consciousness.

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (50)

AT001

Senftenberg, 3541, Austria

Location

AT002

Vienna, 1100, Austria

Location

DE005

Bad Saarow, 15526, Germany

Location

DE007

Berlin, 10435, Germany

Location

DE021

Berlin, 10787, Germany

Location

DE009

Berlin, 12627, Germany

Location

DE030

Berlin, 13125, Germany

Location

DE020

Bochum, 44787, Germany

Location

DE023

Böhlen, 04564, Germany

Location

DE029

Cologne, 50924, Germany

Location

DE008

Cologne, 51069, Germany

Location

DE028

Cottbus, 03050, Germany

Location

DE012

Dresden, 01067, Germany

Location

DE032

Essen, 45355, Germany

Location

DE017

Frankfurt, 60313, Germany

Location

DE003

Frankfurt, 60596, Germany

Location

DE011

Görlitz, 02826, Germany

Location

DE031

Hamburg, 20253, Germany

Location

DE013

Hanover, 30159, Germany

Location

DE001

Kiel, 24105, Germany

Location

DE027

Kiel, 24106, Germany

Location

DE014

Kiel, 24119, Germany

Location

DE004

Leipzig, 04103, Germany

Location

DE034

Leipzig, 04107, Germany

Location

DE018

Leipzig, 04109, Germany

Location

DE015

Magdeburg, 39104, Germany

Location

DE006

Mainz, 55116, Germany

Location

DE002

Mittweida, 09648, Germany

Location

DE010

Rudolstadt, 07407, Germany

Location

DE025

Schwerin, 19055, Germany

Location

DE019

Stadtroda, 07646, Germany

Location

DE016

Weinheim, 69469, Germany

Location

DE024

Westerstede, 26655, Germany

Location

DE026

Wiesbaden, 65185, Germany

Location

DE022

Wiesbaden, 65187, Germany

Location

IT003

Catania, 95125, Italy

Location

IT001

Genova, 16132, Italy

Location

IT002

Parma, 43126, Italy

Location

IT004

Pavia, 27100, Italy

Location

IT005

Varese, 21046, Italy

Location

ES006

A Coruña, 15006, Spain

Location

ES007

Barcelona, 08006, Spain

Location

ES001

Barcelona, 08916, Spain

Location

ES003

Centelles, 08540, Spain

Location

ES008

Guadix, 18500, Spain

Location

ES002

Madrid, 28046, Spain

Location

ES010

Madrid, 28050, Spain

Location

ES009

Madrid, 28850, Spain

Location

ES004

Oviedo, 33009, Spain

Location

ES005

Santiago de Compostela, 15705, Spain

Location

Related Publications (1)

• Baron R, Likar R, Martin-Mola E, Blanco FJ, Kennes L, Muller M, Falke D, Steigerwald I. Effectiveness of Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR for the Management of Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-Label, Phase 3b/4 Study. Pain Pract. 2016 Jun;16(5):580-99. doi: 10.1111/papr.12308. Epub 2015 Jun 12.

  PMID: 26095455 RESULT

MeSH Terms

Conditions

Back Pain; Low Back Pain; Neuralgia; Constipation

Interventions

Tapentadol; Oxycodone

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Codeine; 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

Results Point of Contact

• Title: Study Director
• Organization: Grünenthal GmbH

Clinical-Trials@grunenthal.com

+49 241 569

Study Officials

• Director Clinical Trials

  Grünenthal GmbH

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2013
• First Posted: April 24, 2013
• Study Start: April 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: February 24, 2016
• Results First Posted: June 8, 2015

Record last verified: 2016-01

Locations

AU (2); ES (10); DE (33); IT (5)