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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-022798-32 | EudraCT Number |
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| Name | Class |
|---|---|
| PRA Health Sciences | INDUSTRY |
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The purpose of this study is to evaluate the analgesic efficacy of Dexketoprofen Trometamol and Tramadol Hydrochloride given in combinations and the analgesic efficacy of each single component in comparison to placebo on moderate to severe pain following impacted third mandibular molar tooth extraction. Ibuprofen will be used as an active control to validate the pain model.
The aim of this study is to develop a combination of Dexketoprofen Trometamol (DKP.TRIS) and Tramadol Hydrochloride (TRAM.HCl) for the treatment of acute moderate to severe pain, based on the rationale that more than one drug is necessary in most patients suffering of acute and chronic pain, particularly of moderate to severe intensity.
DKP.TRIS and TRAM.HCl have different mechanisms of action, therefore their combination is expect to result in an additive or synergistic analgesia, thus allowing a decrease in the required doses of the individual agents, and consequently a reduced risk of adverse events In this study, patients who present moderate to severe pain after impacted third mandibular molar tooth extraction will be randomised to a total of 10 treatment arms including 4 combinations of DKP.TRIS + TRAM.HCl, the four corresponding single treatments, placebo and ibuprofen. Treatment administration will be followed by a 24-hour pain and analgesic effect assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Ibuprofen | Active Comparator |
| |
| TRAM.HCl high dose | Active Comparator |
| |
| TRAM.HCl low dose | Active Comparator |
| |
| DKP-TRIS high dose | Active Comparator |
| |
| DKP-TRIS low dose | Active Comparator |
| |
| DKP-TRIS low dose - TRAM.HCl low dose | Experimental |
| |
| DKP-TRIS low dose - TRAM.HCl high dose |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexketoprofen Trometamol | Drug | Dexketoprofen Trometamol low dose, oral film-coated table, once |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 6 Hours Post-dosing. | Pain relief is measured by a verbal rating scale (ranging from 0=none to 4=complete). Theoretical maximum TOTPAR at 6 hours is calculated by summing up the maximum score of analgesia which the patient can attribute at defined time points along 6 hour (maxTOTPAR6h= 24). Unit of measure is % | 6 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 4, 8 and 12 Hours Post-dosing. | Pain relief is measured by a verbal rating scale (ranging from 0=none to 4=complete). Theoretical maximum TOTPAR at 6 hours is calculated by summing up the maximum score of analgesia which the patient can attribute at defined time points along 4, 8 and 12 hours(maxTOTPAR4h= 16, maxTOTPAR8h= 32 and maxTOTPAR12h= 48, respectively) Unit of measure is % |
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Inclusion Criteria:
Patients meeting ALL the following criteria will be eligible for entry into the study:
At randomisation (after surgery):
No intake of analgesics (including prescription and over the counter drugs) within 24h prior to the surgery.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Cosme Gay-Escoda, Professor | Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Barcelona - Bellvitge Institute for Biomedical Research (IDIBELL) 08907 Hospitalet de Llobregat, Barcelona (Spain) | Study Chair |
| R Andrew Moore, Professor | Pain Research & Nuffield Division of Anaesthesics, Department of Clinical Neurosciences, University of Oxford. The Churchill, Oxford OX3 7LJ (United Kingdom) | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Klinik und Polickinik für Mund-Kiefer-Gesichtschirurgie/Plastische Operationen Greifswald | Greifswald | Mecklenburg-Vorpommern | 17475 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26123824 | Derived | Moore RA, Gay-Escoda C, Figueiredo R, Toth-Bagi Z, Dietrich T, Milleri S, Torres-Lagares D, Hill CM, Garcia-Garcia A, Coulthard P, Wojtowicz A, Matenko D, Penarrocha-Diago M, Cuadripani S, Piza-Vallespir B, Guerrero-Bayon C, Bertolotti M, Contini MP, Scartoni S, Nizzardo A, Capriati A, Maggi CA. Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain. J Headache Pain. 2015;16:541. doi: 10.1186/s10194-015-0541-5. Epub 2015 Jun 27. |
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The trial encompassed 3 visits: 1-Screening; 2-Dental surgery (patients who have moderate to severe pain afterwards were randomised and received study drug); 3-End of study. Overall, 745 patients were enrolled (screened), of them 611 were randomized to receive the study drug and therefore considered as started.
First patient in (screening) 23 Feb 2011, last patient out 14 Oct 2011. At 16 study centres in 6 European countries (Germany, Italy, Hungary, Poland, Spain and United Kingdom).
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| ID | Title | Description |
|---|---|---|
| FG000 | DKP-TRIS 12.5mg - TRAM.HCl 37.5mg | DKP-TRIS 12.5mg - TRAM.HCl 37.5mg oral film-coated tablet, once |
| FG001 | DKP-TRIS 12.5mg - TRAM.HCl 75mg | DKP-TRIS 12.5mg - TRAM.HCl 75mg oral film-coated tablet, once |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Experimental |
|
| DKP-TRIS high dose - TRAM.HCl low dose | Experimental |
|
| DKP-TRIS high dose - TRAM.HCl high dose | Experimental |
|
| Dexketoprofen Trometamol | Drug | Dexketoprofen Trometamol high dose, oral film-coated table, once |
|
| Tramadol Hydrochloride | Drug | Tramadol Hydrochloride low dose, oral film-coated table, once |
|
| Tramadol Hydrochloride | Drug | Tramadol Hydrochloride high dose, oral film-coated table, once |
|
| Ibuprofen | Drug | Ibuprofen 400 mg, oral film-coated table, once |
|
| Placebo | Drug | Placebo, oral film-coated table, once |
|
| Dexketoprofen Trometamol + Tramadol Hydrochloride | Drug | DKP-TRIS low dose - TRAM.HCl low dose, oral film-coated table, once |
|
| Dexketoprofen Trometamol + Tramadol Hydrochloride | Drug | DKP-TRIS low dose - TRAM.HCl high dose, oral film-coated table, once |
|
| Dexketoprofen Trometamol + Tramadol Hydrochloride | Drug | DKP-TRIS high dose - TRAM.HCl low dose, oral film-coated tablet, once |
|
| Dexketoprofen Trometamol + Tramadol Hydrochloride | Drug | DKP-TRIS high dose - TRAM.HCl high dose, oral film-coated tablet, once |
|
| 4, 8 and 12 hours |
| Percentage of Patients Using Rescue Medication at 6 Hours | Percentage of patients using rescue medication at 6 hours post-dosing. | Baseline to 6 hours |
| Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Schleswig Holstein, Campus Kiel | Kiel | Schleswig-Holstein | 24105 | Germany |
| Dr Tóth Bagi Zoltán Fogászati Rendeloje | Budapest | Budapest | 1052 | Hungary |
| Centro di Farmacologia Clinica per la Sperimentazione dei Farmaci | Pisa | Pisa | 56126 | Italy |
| Centro di Ricerche Cliniche di Verona Srl. Policlinico G.B.Rossi | Verona | Verona | 37134 | Italy |
| Gabinet Stomatologiczny Andrzej Wojtowicz AW Clinic | Warsaw | Masovian Voivodeship | 00-852 | Poland |
| Dental Service spólka jawna | Warsaw | Masovian Voivodeship | 02-791 | Poland |
| Hospital Médico Quirúrgico de Conxo | Santiago de Compostela | A Coruña | 15706 | Spain |
| Facultad de OdontologÃa. Departamento de CirugÃa Bucal y Maxilofacial, University of Barcelona - Bellvitge Institute for Biomedical Research (IDIBELL) | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| Universidad Complutense de Madrid | Madrid | Madrid | 28040 | Spain |
| Departamento de EstomatologÃa, Facultad de OdontologÃa. Universidad de Sevilla | Seville | Sevilla | 41009 | Spain |
| Departament d'Estomatologia, ClÃnica Odontològica, Universidad de Valencia - Fundació LluÃs AlcanyÃs | Valencia | Valencia | 046010 | Spain |
| Hospital General Universitario de Valencia | Valencia | Valencia | 46014 | Spain |
| The School of Dentistry, College of Medical and Dental Sciences, University of Birmingham | Birmingham | England | B4 6 NN | United Kingdom |
| University Dental School Manchester | Manchester | England | M15 6FH | United Kingdom |
| University Dental Hospital | Cardiff | Wales | CF14 4 XY | United Kingdom |
| FG002 | DKP-TRIS 25mg - TRAM.HCl 37.5mg | DKP-TRIS 25mg - TRAM.HCl 37.5mg oral film-coated tablet, once |
| FG003 | DKP-TRIS 25mg - TRAM.HCl 75mg | DKP-TRIS 25mg - TRAM.HCl 75mg oral film-coated tablet, once |
| FG004 | DKP-TRIS 12.5mg | DKP-TRIS 12.5mg oral film-coated tablet, once |
| FG005 | DKP-TRIS 25mg | DKP-TRIS 25mg oral film-coated tablet, once |
| FG006 | TRAM.HCl 37.5mg | TRAM.HCl 37.5mg oral film-coated tablet, once |
| FG007 | TRAM.HCl 75mg | TRAM.HCl 75mg oral film-coated tablet, once |
| FG008 | Ibuprofen 400mg | Ibuprofen 400mg oral film-coated tablet, once |
| FG009 | Placebo | Placebo oral film-coated tablet, once |
| Safety Population |
|
| ITT (>= 1 Assessment Post Randomization) |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | DKP-TRIS 12.5mg - TRAM.HCl 37.5mg | DKP-TRIS 12.5mg - TRAM.HCl 37.5mg oral film-coated tablet, once |
| BG001 | DKP-TRIS 12.5mg - TRAM.HCl 75mg | DKP-TRIS 12.5mg - TRAM.HCl 75mg oral film-coated tablet, once |
| BG002 | DKP-TRIS 25mg - TRAM.HCl 37.5mg | DKP-TRIS 25mg - TRAM.HCl 37.5mg oral film-coated tablet, once |
| BG003 | DKP-TRIS 25mg - TRAM.HCl 75mg | DKP-TRIS 25mg - TRAM.HCl 75mg oral film-coated tablet, once |
| BG004 | DKP-TRIS 12.5mg | DKP-TRIS 12.5mg oral film-coated tablet, once |
| BG005 | DKP-TRIS 25mg | DKP-TRIS 25mg oral film-coated tablet, once |
| BG006 | TRAM.HCl 37.5mg | TRAM.HCl 37.5mg oral film-coated tablet, once |
| BG007 | TRAM.HCl 75mg | TRAM.HCl 75mg oral film-coated tablet, once |
| BG008 | Ibuprofen 400mg | Ibuprofen 400mg oral film-coated tablet, once |
| BG009 | Placebo | Placebo oral film-coated tablet, once |
| BG010 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| BMI | Body Mass Index (measured in kg/m^2) | Mean | Standard Deviation | kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 6 Hours Post-dosing. | Pain relief is measured by a verbal rating scale (ranging from 0=none to 4=complete). Theoretical maximum TOTPAR at 6 hours is calculated by summing up the maximum score of analgesia which the patient can attribute at defined time points along 6 hour (maxTOTPAR6h= 24). Unit of measure is % | ITT (intention to treat) population which was defined as all patients who have taken the study treatment and have at least 1 post-dose assessment | Posted | Number | percentage of patients | 6 hours |
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 4, 8 and 12 Hours Post-dosing. | Pain relief is measured by a verbal rating scale (ranging from 0=none to 4=complete). Theoretical maximum TOTPAR at 6 hours is calculated by summing up the maximum score of analgesia which the patient can attribute at defined time points along 4, 8 and 12 hours(maxTOTPAR4h= 16, maxTOTPAR8h= 32 and maxTOTPAR12h= 48, respectively) Unit of measure is % | ITT (intention to treat) population which was defined as all patients who have taken the study treatment and have at least 1 post-dose assessment | Posted | Number | percentage of patient | 4, 8 and 12 hours |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Patients Using Rescue Medication at 6 Hours | Percentage of patients using rescue medication at 6 hours post-dosing. | ITT (intention to treat) population which was defined as all patients who have taken the study treatment and have at least 1 post-dose assessment | Posted | Number | percentage of patients | Baseline to 6 hours |
|
10 ± 3 days
Analyzed for the Safety population (all patients who received study treatment)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DKP-TRIS 12.5mg - TRAM.HCl 37.5mg | DKP-TRIS 12.5mg - TRAM.HCl 37.5mg oral film-coated tablet, once | 0 | 61 | 7 | 61 | ||
| EG001 | DKP-TRIS 12.5mg - TRAM.HCl 75mg | DKP-TRIS 12.5mg - TRAM.HCl 75mg oral film-coated tablet, once | 0 | 63 | 9 | 63 | ||
| EG002 | DKP-TRIS 25mg - TRAM.HCl 37.5mg | DKP-TRIS 25mg - TRAM.HCl 37.5mg oral film-coated tablet, once | 0 | 63 | 6 | 63 | ||
| EG003 | DKP-TRIS 25mg - TRAM.HCl 75mg | DKP-TRIS 25mg - TRAM.HCl 75mg oral film-coated tablet, once | 0 | 61 | 10 | 61 | ||
| EG004 | DKP-TRIS 12.5mg | DKP-TRIS 12.5mg oral film-coated tablet, once | 0 | 60 | 2 | 60 | ||
| EG005 | DKP-TRIS 25mg | DKP-TRIS 25mg oral film-coated tablet, once | 0 | 61 | 4 | 61 | ||
| EG006 | TRAM.HCl 37.5mg | TRAM.HCl 37.5mg oral film-coated tablet, once | 0 | 59 | 5 | 59 | ||
| EG007 | TRAM.HCl 75mg | TRAM.HCl 75mg oral film-coated tablet, once | 1 | 60 | 14 | 60 | ||
| EG008 | Ibuprofen 400mg | Ibuprofen 400mg oral film-coated tablet, once | 0 | 61 | 5 | 61 | ||
| EG009 | Placebo | Placebo oral film-coated tablet, once | 0 | 62 | 1 | 62 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDra 13.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDra 13.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDra 13.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDra 13.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDra 13.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDra 13.1 | Non-systematic Assessment |
|
Prior to submitting the results of this study for publication or presentation, the investigator will allow the Sponsor at least 60 days time to review and comment upon the publication manuscript. It is agreed, that the results of the study will not be submitted for presentation, abstract, poster exhibition, or publication by the investigator until the Sponsor has reviewed/commented and agreed to any publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Angela Capriati, Corporate Clinical Research Director | Menarini Ricerche S.p.A. | +39 055 5680 9933 | acapriati@menarini-ricerche.it |
| ID | Term |
|---|---|
| D010146 | Pain |
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| C118296 | dexketoprofen trometamol |
| D014147 | Tramadol |
| D007052 | Ibuprofen |
| ID | Term |
|---|---|
| D003511 | Cyclohexanols |
| D000441 | Hexanols |
| D005233 | Fatty Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D004123 | Dimethylamines |
| D008744 | Methylamines |
| D000588 | Amines |
| D008055 | Lipids |
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
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| Male |
|
DKP-TRIS 25mg - TRAM.HCl 75mg oral film-coated tablet, once |
| OG004 | DKP-TRIS 12.5mg | DKP-TRIS 12.5mg oral film-coated tablet, once |
| OG005 | DKP-TRIS 25mg | DKP-TRIS 25mg oral film-coated tablet, once |
| OG006 | TRAM.HCl 37.5mg | TRAM.HCl 37.5mg oral film-coated tablet, once |
| OG007 | TRAM.HCl 75mg | TRAM.HCl 75mg oral film-coated tablet, once |
| OG008 | Ibuprofen 400mg | Ibuprofen 400mg oral film-coated tablet, once |
| OG009 | Placebo | Placebo oral film-coated tablet, once |
|
|
DKP-TRIS 12.5mg oral film-coated tablet, once |
| OG005 | DKP-TRIS 25mg | DKP-TRIS 25mg oral film-coated tablet, once |
| OG006 | TRAM.HCl 37.5mg | TRAM.HCl 37.5mg oral film-coated tablet, once |
| OG007 | TRAM.HCl 75mg | TRAM.HCl 75mg oral film-coated tablet, once |
| OG008 | Ibuprofen 400mg | Ibuprofen 400mg oral film-coated tablet, once |
| OG009 | Placebo | Placebo oral film-coated tablet, once |
|
|