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Effects of GABA Modulator AZD7325 on Cutaneous Sensation

26 de julio de 2016 actualizado por: University College, London

A Phase I Single Site, Single Dose, Randomized, Double-blind, Placebo Controlled, 2-way Cross-over Biomarker Study Investigating the Effect of the GABA Modulator AZD7325 on Cutaneous Sensation in Healthy Volunteers

GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the human brain. For years, drugs that enhance its effects (e.g., benzodiazepines such as diazepam/Valium) have been used to treat various diseases such as epilepsy, insomnia, anxiety or movement disorders. However, the use of these medications is often compromised because of their side effects, such as sleepiness, memory problems, and addiction.

Therefore, effort has been made to develop drugs that act more selectively in the brain to exert the positive therapeutic effects and are devoid of the unwanted side effects. AZD7325 is one of these drugs. It has been tested in more than 700 people and so far proved to be generally well tolerated. Positron emission tomography (PET) study in humans demonstrated that AZD7325 binds to GABA A receptors in the brain after a single dose. Early clinical studies have shown that it has less sedative and cognitive adverse events as compared with a benzodiazepine lorazepam.

The investigators now wish to evaluate if effects of AZD7325 can be objectively measured in healthy volunteers and to establish which of the drug's outcomes could be utilised for further studies in patients with neurological diseases.

The investigators are especially interested in the effects of AZD7325 on manual dexterity and skin sensation of the hand. This can be assessed by a number of simple non-invasive tests of object manipulation and detection of different sensory stimuli such as touch, vibration, or temperature. Recent studies show that healthy individuals who performed better in similar tasks had more GABA in relevant areas of their brain. If performance in these tasks in healthy volunteers can be improved by enhancing GABA effects in the brain with AZD7325, this would create the grounds for the use of this medication to treat symptoms of certain neurological disorders in which motor control and sensation of the hand is impaired (e.g., polyneuropathy).

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

12

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

      • London, Reino Unido, WC1N 3BG
        • National Hospital For Neurology and Neurosurgery

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

Géneros elegibles para el estudio

Masculino

Descripción

Inclusion Criteria:

  • Male adults aged 18 to 55 years (extremes are included)
  • A body weight resulting in a body mass index (BMI) of 18-30 kg/m2 (extremes included) using the formula BMI = body-weight [in kg] / body-height [in m]2
  • Able and willing to sign the Informed Consent Form prior to screening evaluations.
  • History of good physical and mental health as determined by history taking and laboratory examinations, ECG, blood pressure and heart rate recordings as judged by the investigator
  • Willing not to consume alcohol or to smoke or chew tobacco on days of assessments
  • Subjects must be willing to avoid unprotected vaginal intercourse with women of child bearing potential (see above under 3.5) or donating sperm for the duration of the study and a further 1 week after drug administration.

Exclusion Criteria:

  • History of allergy/idiosyncrasy to AZD7325 or chemically related compounds or excipients which may be employed in the study or to any other drug used in the past
  • Subject has taken systemically (po, iv) any potent or moderate CYP3A4 or CYP2C9 inhibitor, 1 month prior to screening (topical or inhaled are permitted) such as: aprepitant, barbiturates, carbamazepine, clarithromycin, erythromycin, cyclosporine, diltiazem, efavirenz, fluconazole, HIV protease inhibitors, glucocorticoids, itraconazole (oral/IV), ketoconazole, nefazodone, nevirapine, phenytoin, pioglitazone, primidone, rifabutin, rifampicin, telithromycin, St. John's wort, verapamil
  • Use of any prescription drug judged by the investigator as potentially interfering with this trial within two weeks prior to the first dosing, except for topical medication without systemic exposure
  • Clinically relevant history or presence of any medical disorder, potentially interfering with this trial
  • Clinically relevant abnormal laboratory, ECG, HR or BP at screening as judged by the investigator
  • History of or current abuse of drugs (including prescription medication) or alcohol or solvents
  • Smoking in excess of 5 cigarettes per day or the equivalent within 28 days prior to the screening visit
  • Smoking or chewing of tobacco or consume of alcohol, 24 hours before and on the days of assessment
  • Subject is family member or in the employment line management of study personnel
  • Subject has abnormal screening laboratory values
  • Subject's partner is planning pregnancy within 3 months of last dosing
  • Participation in an IMP intervention trial within last month or more than four in the previous 12 months
  • Abnormal responses in the object manipulation task and psychophysical measures, SDMT, VAS outside 95% confidence interval of normal at screening visit
  • Subjects with a history of epilepsy, seizures or episodes of unexplained and unprovoked loss of consciousness

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: Ciencia básica
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación cruzada
  • Enmascaramiento: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 20 mg AZD7325
10 mg AZD7325 in orange capsule, Size 0, 2 capsules as a single oral dose
Una sola dosis oral
A single 20 mg oral dose of AZD7325
Comparador de placebos: Placebo
10 mg Microcrystalline cellulose in orange capsule, Size 0, 2 capsules as a single oral dose
Una sola dosis oral
A single 20 mg oral dose of AZD7325

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Change in peak grip force in an object manipulation task
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
from baseline at 1, 2, and 3 hours after the study medication

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Changes in parameters of object manipulation in a object manipulation task (grip force rate)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: grip force rate
from baseline at 1, 2, and 3 hours after the study medication
Changes in parameters of object manipulation in a object manipulation task (load force rate)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: load force rate
from baseline at 1, 2, and 3 hours after the study medication
Changes in parameters of object manipulation in a object manipulation task (static load force)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: static load force
from baseline at 1, 2, and 3 hours after the study medication
Changes in parameters of object manipulation in a object manipulation task (static grip force)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: static grip force
from baseline at 1, 2, and 3 hours after the study medication
Changes in parameters of object manipulation in a object manipulation task (9-hole pegboard test)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: 9-hole pegboard test
from baseline at 1, 2, and 3 hours after the study medication
Changes in performance in the psychophysical tests of cutaneous sensation ("bumps" test)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: "bumps" test
from baseline at 1, 2, and 3 hours after the study medication
Changes in performance in the psychophysical tests of cutaneous sensation (grating orientation task)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: grating orientation task
from baseline at 1, 2, and 3 hours after the study medication
Changes in performance in the psychophysical tests of cutaneous sensation (vibrotactile sensitivity)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: vibrotactile sensitivity
from baseline at 1, 2, and 3 hours after the study medication
Changes in performance in the psychophysical tests of cutaneous sensation (thermal sensitivity)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
Parameters: thermal sensitivity
from baseline at 1, 2, and 3 hours after the study medication
Change in the rating on a 0-100 mm Visual Analogue Scale (VAS) of degree of sedation
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
from baseline at 1, 2, and 3 hours after the study medication
Change in the score of Symbol Digit Modalities Test (SDMT)
Periodo de tiempo: from baseline at 1, 2, and 3 hours after the study medication
from baseline at 1, 2, and 3 hours after the study medication
Safety and tolerability of a single dose of AZD7325 by assessment of adverse events, vital signs, physical examination, ECG, and laboratory variables
Periodo de tiempo: 3 times during the trial period, an expected average of 4 weeks (before each dose and 48-96 hours after the last dose of study medication). Adverse events also at follow-up telephone call within a week after the last dose of study medication
Composite outcome measure
3 times during the trial period, an expected average of 4 weeks (before each dose and 48-96 hours after the last dose of study medication). Adverse events also at follow-up telephone call within a week after the last dose of study medication

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Investigadores

  • Investigador principal: Martin Koltzenburg, Prof, Institute of Neurology, University College London

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

1 de febrero de 2016

Finalización primaria (Actual)

1 de julio de 2016

Finalización del estudio (Actual)

1 de julio de 2016

Fechas de registro del estudio

Enviado por primera vez

3 de agosto de 2015

Primero enviado que cumplió con los criterios de control de calidad

19 de agosto de 2015

Publicado por primera vez (Estimar)

21 de agosto de 2015

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

27 de julio de 2016

Última actualización enviada que cumplió con los criterios de control de calidad

26 de julio de 2016

Última verificación

1 de julio de 2016

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • 13/0261
  • 2015-000642-35 (Número EudraCT)

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. .

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