E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with moderate to severe dental pain |
Pacientes adultos con dolor dental de moderado a severo |
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E.1.1.1 | Medical condition in easily understood language |
Pain after oral surgery |
Dolor después de cirugía dental |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033371 |
E.1.2 | Term | Pain |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish the effective dose between 4 strenghts of E-58425 for moderate to severe dental pain |
Establecer la dosis efective entre 4 de E-58425 en dolor dental de moderado a severo |
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E.2.2 | Secondary objectives of the trial |
To asses the efficacy and safety of E-58425 |
Evaluar la eficacia y seguridad del E-58425 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Establish plasma concentrations of E-58425 |
Establecer concentraciones plasmáticas de E-58425 |
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E.3 | Principal inclusion criteria |
-Moderate or severe pain (score of at least 50mm on VAS) as a result of an oral surgical procedure under local anesthesia and/or sedation. The procedure must have involved extraction of at least two impacted third molars requiring bone removal. If only two impacted third molars are extracted, they must be ipsilateral and require bone removal. |
-Dolor de moderado a intenso (puntuación de al menos 50 mm en VAS) como resultado de una intervención quirúrgica bucal bajo anestesia local y/o sedación. El procedimiento debe haber incluido la extracción de al menos dos terceros molares impactados que requiere eliminación de hueso. Si sólo se extraen dos terceros molares impactados, deben ser ipsolatelares y requerir eliminación de hueso. |
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E.4 | Principal exclusion criteria |
-Received any analgesic medication other than short-acting preoperative or intraoperative anesthetic agents within 12 hours before taking trial medication. -Patients who received any analgesic medication other than the study drug immediately after the oral surgical procedure was completed will also be excluded. -Patients with any complication during surgery. -Received a long-acting nonsteroidal anti-inflammatory drug (NSAID) within three days prior to dosing. -History of seizures or drug or alcohol abuse within six months. -Received monoamine oxidase inhibitors, tricyclic antidepressants, neuroleptics, or other drugs that reduce the seizure threshold within four weeks of study entry. -Evidence of renal or hepatic dysfunction, or peptic ulcer disease. -Received selective serotonin reuptake inhibitors (SSRIs) (e.g. paroxetine, fluoxetine), diet pills (including fenfluramine, phentermine, etc.), or methylphenidate (Ritalin®) within four weeks of study entry. -Sensitive or allergic to tramadol, celecoxib or other NSAIDs, or aspirin. -At risk in terms of precautions, warnings, and contraindications in the package insert for Adolonta® tramadol hydrochloride, Celebrex® celecoxib. -Coagulation disorders. -Non controlled high blood pressure, diabetes or cardiac failure. -Asthma or history of bronchospasm. |
-Haber recibido cualquier medicación analgésica distinta a los agentes anestésicos preoperatorios o intraoperatorios de corta duración en el plazo de las 12 horas previas a tomar la medicación del ensayo -Pacientes que recibieron cualquier medicación analgésica distinta del fármaco del estudio inmediatamente después de completada la intervención quirúrgica bucal -Pacientes con cualquier complicación durante la cirugía -Haber recibido un fármaco antiinflamatorio no esteroideo (AINE) de acción prolongada en el plazo de los tres días previos a la dosificación -Historia de convulsiones o alcoholismo o drogadicción en el plazo de seis meses -Haber recibido inhibidores de monoaminooxidasa, antidepresivos tricíclicos, neurolépticos, u otros fármacos que reducen el umbral de convulsiones en el plazo de cuatro semanas de la entrada en el estudio -Evidencia de disfunción renal o hepática, o enfermedad de úlcera péptica -Haber recibido inhibidores selectivos de la recaptación de serotonina (ISRS) (por ejemplo, paroxetina, fluoxetina), píldoras dietéticas (incluyendo fenfluramina, fentermina, etc.), o metilfenidato (Ritalin®) en el plazo de cuatro semanas de la entrada en el estudio -Ser sensible o alérgico a tramadol, celecoxib u otros AINE, o a la aspirina -En riesgo en lo que se refiere a precauciones, advertencias, y contraindicaciones en el prospecto para Adolonta® tramadol clorhidrato, Celebrex® celecoxib -Trastornos de coagulación -Tensión arterial alta, diabetes o insuficiencia cardiaca no controladas -Asma o historia de broncoespasmo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Analgesic efficacy measurements that will include pain intensity, pain relief, use of rescue medication, time to perceptible and meaningful pain relief and overall assessment of the study medication. |
Las mediciones de la eficacia analgésica incluirán intensidad del dolor, alivio del dolor, uso de medicación de rescate, tiempo hasta lograr un alivio del dolor perceptible y significativo y evaluación global de la medicación del estudio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pain intensity will be assessed by the Visual Analogue Scale. Baseline pain and pain at 10 min, 20min, 30min, 45min, 1h, 1h 15min, 1h 30min, 1h 45min, 2 h, 2h 15min, 2h 30min, 2h 45min, 3h, 3h 15min, 3h 30min, 3h 45min, 4h, 4h 30 min, 5h, 5h 30 min, 6h, 7h, 8h, 10h, 12h and 24h after receiving the study medication. |
La intensidad del dolor se evaluará mediante la escala analógica visual (VAS). Se registrará el dolor de nivel inicial y el dolor a los 10 min., 20 min., 30 min., 45 min., 1 h, 1 h 15 min., 1 h 30 min., 1 h 45 min., 2 h, 2 h 15 min., 2 h 30 min., 2 h 45 min., 3 h, 3 h 15 min., 3 h 30 min., 3 h 45 min., 4 h, 4 h 30 min., 5 h, 5 h 30 min., 6 h, 7 h, 8 h, 10 h, 12 h y 24 h tras recibir la medicación del estudio |
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E.5.2 | Secondary end point(s) |
Plasma concentrations of E-58425 Safety and tolerability: Adverse (AEs), Safety laboratory tests, Dental evaluation, General medical examination, Vital signs (pulse rate and blood pressure in sitting position, body temperature), 12-lead ECG (PR-, QRS-, QT and QTc-intervals) |
Concentraciones plasmáticas de E-58425 Seguridad y tolerancia: Acontecimientos adversos (AA), Pruebas de laboratorio de seguridad, Evaluación dental, Examen médico general, Signos vitales (pulso y tensión arterial sentado, temperatura corporal), ECG de 12 derivaciones (Intervalos PR- QRS, QT y QTc) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Blood samples will be taken from patients of at least one study centre at 0, 2 and 6 hours after administration of the study medication or at the time the patient decides to withdraw from the study (if the patient consents) for determination of plasma levels of E-58425 (Tramadol, M1 and celecoxib). Safety and tolerability: up to one week |
Se extraerán muestras de sangre de los pacientes de al menos un centro de estudio a las 0, 2 y 6 horas tras la administración de la medicación del estudio o en el momento en que el paciente decide retirarse del estudio (si el paciente da su consentimiento) para la determinación de los niveles plasmáticos de E-58425 (Tramadol, M1 y celecoxib). Seguridad y tolerancia: hasta 1 semana |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study ends with the last visit of the last patient participating in the trial. |
LVLS |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |