- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01371799
A Study to Examine the Pharmacodynamic Effects of GSK1034702 on Neurophysiological Biomarkers of Cognition in Nicotine Abstained Otherwise Healthy Smokers (MAA113746)
12 de junio de 2017 actualizado por: GlaxoSmithKline
A Double Blind, Randomized, Placebo Controlled, Cross-over Study to Examine the Pharmacodynamic Effects of GSK1034702 on Neurophysiological Biomarkers of Cognition in Nicotine Abstained Otherwise Healthy Smokers
This will be a double blind, randomised, placebo controlled, cross over study in which up to 20 otherwise healthy male nicotine abstinent smokers will be tested following 3 acute treatment conditions (placebo, 4 and 8mg of GSK1034702).
Each subject will undergo screening assessments within 30 days prior to administration of the first dose of study medication.
There will be 3 treatment sessions and dosing will be separated by a minimum 1 week washout period.
There will be two testing days (day 1 and day 2) per treatment session.
On each treatment session subjects will be admitted on day 1.
On day 1, subjects will be administered placebo and approximately 3 hours later, there will be a Baseline EEG/ERP recording, neuropsychological (Cogstate battery) testing and mood/craving/dependence questionnaire assessments .
Subjects will be allowed to smoke until approximately midnight on day 1.
On day 2, subjects will undergo a pre-drug neuropsychological (Cogstate battery) testing and questionnaire assessments of mood/craving.
This will be conducted approximately 1 hour prior to dosing.
Subjects will be randomized to one of six treatment sequences.
Post dose EEG/ERP recording, neuropsychological (Cogstate battery) testing and mood/craving measurements will be conducted between 3 and 6 hours post treatment to coincide with peak pharmacokinetic effects.
This testing will be performed approximately at 12pm following at least 12hrs of nicotine abstinence.
Blood samples will be collected at baseline (pre-drug) and following drug administration to quantify exposure levels.
Descripción general del estudio
Tipo de estudio
Intervencionista
Inscripción (Actual)
9
Fase
- Fase 1
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
-
Cambridge, Reino Unido, CB2 2GG
- GSK Investigational Site
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 55 años (Adulto)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Masculino
Descripción
Inclusion Criteria A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Otherwise healthy smokers as determined by a responsible physician, based on a medical evaluation including own and familial medical history, physical examination, psychiatric history, psychiatric evaluation, laboratory tests and cardiac monitoring.
- A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Subjects must have QTc values within the normal range, i.e. QTcB or QTcF < 450 msec. The following normal ranges for blood pressure and heart rate are given as a guide: Systolic blood pressure ≥90 and ≤140 mmHg Diastolic blood pressure ≥60 and ≤90 mmHg Heart rate ≥50 and ≤90 bpm - Male subjects between 18 and 55 years of age.
- Male subjects must agree to use one of the contraception methods listed in Section 8.1.1. This criterion must be followed from the time of the first dose of study medication until 3 months post-last dose.
- Subject is a smoker, i.e. on average smokes 10 or more cigarettes per day for at least 1 year prior to the screening visit. Urinary cotinine levels indicative of smoking at screening.
- Body weight > 50 kg and BMI within the range 19 - 29.9 kg/m2 (inclusive).
- Subjects must have AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Tests may be repeated once but must be within the above limits by the day one visit.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion Criteria
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Current or past diagnosis of psychiatric disorder, as assessed by the MINI.
- Subjects, who in the investigator's judgement, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months.
- Current or past diagnosis of cardiovascular disease including but not limited to hypertension, cardiac arrhythmias, personal or family history of long QT syndrome, cardiac conduction disorder and/or risk factors for coronary artery disease (i.e. family history in more than 2 first degree relatives) or other clinically significant cardiac disease
- Current or past diagnosis of cerebrovascular disease (e.g., stroke, transient ischemic attacks, aneurysms).
- Current or past diagnosis of autonomic dysfunction (e.g. prone to fainting, orthostatic hypotension). Current or past diagnosis of acute or chronic respiratory disease (excluding childhood asthma and allergic rhinitis) and/or abnormal spirometry for age, sex and height at screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Subjects with a history of gastrointestinal bleeding and/or a history of peptic ulcer disease and/or presence of active gastrointestinal disease.
- Subjects with an unstable medical disorder or a disorder (including surgical interventions) that would likely interfere with the action, absorption, distribution, metabolism or excretion of GSK1034702, may pose a safety concern, or interfere with accurate assessment of safety.
- History of regular alcohol consumption within 6 months of the study defined as: For males: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units. One unit is equivalent to a half-pint (220 mL) of beer or 1 (125 mL) measure of spirits or 1 glass (125 mL) of wine.
- A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort and Gingko biloba) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice (and exotic citrus fruits, grapefruit hybrids or fruit juices) from 7 days prior to the first dose of study medication.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period.
- Unwillingness or inability to follow the procedures outlined in the protocol
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Comparador de placebos: Placebo
|
Placebo
4mg and 8mg Study drug
|
Experimental: Study drug at 4mg
GSK1034702 at 4mg
|
Placebo
4mg and 8mg Study drug
|
Experimental: Study drug at 8mg
GSK1034702 at 8mg
|
Placebo
4mg and 8mg Study drug
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Measures will include changes in cognition measures of specific biomarkers
Periodo de tiempo: 12 months
|
To investigate the effects of GSK1034702 on the mismatch negativity neurophysiologic marker of cognition.
|
12 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Measures will include changes in the neurophysiologic markers of cognition
Periodo de tiempo: 12 Months
|
To investigate the effects of GSK1034702 on other neurophysiologic markers of cognition including, P50 suppression, P300, PPI and synchronized oscillations.
|
12 Months
|
Measures of changes in cognition biomarkers vs. the stduy drug
Periodo de tiempo: 12 months
|
To investigate the relationship between changes in the above neurophysiologic markers of cognitive function and drug exposure
|
12 months
|
Measures of cogstate tests of attention in tests mentioned To investigate the effects of GSK1034702 on Cogstate neuropsychologic tests of attention, working memory, learning and executive function
Periodo de tiempo: 12 months
|
To investigate the effects of GSK1034702 on Cogstate neuropsychologic tests of attention, working memory, learning and executive function
|
12 months
|
Measures of difference between the tests in cogstate and the drug levels at different concentrations To investigate the relationship between changes in Cogstate behavioural task performance and drug exposure
Periodo de tiempo: 12 months
|
To investigate the relationship between changes in Cogstate behavioural task performance and drug exposure
|
12 months
|
Safety measures and PK parameters and PK parameters will be measures, Vital signs, BP. To obtain further safety and PK information following oral administration of GSK1034702 to healthy subjects
Periodo de tiempo: 12 months
|
To obtain further safety and PK information following oral administration of GSK1034702 to healthy subjects
|
12 months
|
Measures in modd/craving To investigate changes in mood/craving in the nicotine "on" state (baseline), following nicotine abstinence and following treatment
Periodo de tiempo: 12 months
|
To investigate changes in mood/craving in the nicotine "on" state (baseline), following nicotine abstinence and following treatment
|
12 months
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- te Beek ET, Hay JL, Bullman JN, Burgess C, Nahon KJ, Klaassen ES, Gray FA, van Gerven JM. Pharmacokinetics and central nervous system effects of the novel dual NK1 /NK3 receptor antagonist GSK1144814 in alcohol-intoxicated volunteers. Br J Clin Pharmacol. 2013 May;75(5):1328-39. doi: 10.1111/bcp.12004.
- Nathan PJ, Watson J, Lund J, Davies CH, Peters G, Dodds CM, Swirski B, Lawrence P, Bentley GD, O'Neill BV, Robertson J, Watson S, Jones GA, Maruff P, Croft RJ, Laruelle M, Bullmore ET. The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction. Int J Neuropsychopharmacol. 2013 May;16(4):721-31. doi: 10.1017/S1461145712000752. Epub 2012 Aug 29.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
17 de diciembre de 2009
Finalización primaria (Actual)
18 de junio de 2010
Finalización del estudio (Actual)
18 de junio de 2010
Fechas de registro del estudio
Enviado por primera vez
14 de abril de 2011
Primero enviado que cumplió con los criterios de control de calidad
9 de junio de 2011
Publicado por primera vez (Estimar)
13 de junio de 2011
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
14 de junio de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
12 de junio de 2017
Última verificación
1 de junio de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 113746
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Datos del estudio/Documentos
-
Conjunto de datos de participantes individuales
Identificador de información: 113746Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
-
Especificación del conjunto de datos
Identificador de información: 113746Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
-
Plan de Análisis Estadístico
Identificador de información: 113746Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
-
Formulario de consentimiento informado
Identificador de información: 113746Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
-
Protocolo de estudio
Identificador de información: 113746Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
-
Informe de estudio clínico
Identificador de información: 113746Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Desordenes mentales
-
Chinese University of Hong KongAún no reclutandoSalud Mental Bienestar 1 | Bienestar mental | Problema de salud mental | Salud mental de precisiónHong Kong
-
Chinese University of Hong KongTerminadoBienestar mental | Alfabetización en salud mentalHong Kong
-
King's College LondonTerminadoSalud Mental Bienestar 1 | Problema de salud mentalReino Unido
-
Chinese University of Hong KongTerminadoSalud Mental Bienestar 1 | Bienestar mental | Problema de salud mentalHong Kong
-
Norwegian Institute of Public HealthTerminadoSalud Mental Bienestar 1 | Estrés mental | Depresión mentalNoruega
-
Manuel StadtmannBerufs- und Weiterbildungszentrum für Gesundheits- und Sozialberufe St.Gallen...Inscripción por invitaciónSalud Mental Bienestar 1 | Problema de salud mental | Trastorno mental en la adolescencia | Desarrollo Adolescente | Estigma social | Salud Mental Bienestar 2Suiza
-
Indiana UniversityCommunity Health Network; Boys & Girls Clubs of IndianapolisReclutamientoSalud Mental Bienestar 1 | Comportamiento infantil | Comportamiento adolescente | Salud Mental Bienestar 2Estados Unidos
-
Education University of Hong KongBaptist Oi Kwan Social ServiceTerminadoEnfermedad mental graveHong Kong
-
Lund UniversityActivo, no reclutando
Ensayos clínicos sobre Drug
-
Skane University HospitalTerminadoEnfermedades Vasculares
-
Lyra TherapeuticsTerminadoSinusitis crónicaNueva Zelanda, Australia
-
Washington University School of MedicineTerminadoFilariasis linfatica | Oncocercosis | Infecciones por helmintos transmitidos por el suelo (STH)Liberia
-
Mclean HospitalNational Institute on Drug Abuse (NIDA)TerminadoDependencia del cannabis | Dependencia de la marihuanaEstados Unidos
-
Laboratorios Andromaco S.A.Terminado
-
Kurume UniversityEisai Inc.; Mebix IncTerminado
-
Omer KaracaBaskent UniversityTerminadoTerapia de ultrasonido; ComplicacionesPavo
-
Mclean HospitalBrain & Behavior Research FoundationTerminadoDependencia del cannabis | Dependencia de la marihuanaEstados Unidos