AZD8108 SAD/MAD in Healthy Volunteers (AZD8108)
9 mars 2017 mis à jour par: AstraZeneca
A Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AZD8108 in Healthy Volunteers
This is a randomized, double-blind, placebo-controlled study of single and multiple ascending dosage levels of AZD8108 in healthy volunteers.
The study includes an up to 28-day screening period, an in-house period during which AZD8108 or placebo will be administered orally as a solution, and a 4- to 10-day follow-up period after discharge.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
In Part 1 of the study (single ascending dose portion), approximately 32 subjects will be randomly assigned.
Eight (8) subjects will be randomized in each of 4 dosage-level cohorts (AZD8108 or placebo).
Within each cohort, 6 subjects will be randomized to receive AZD8108 and 2 subjects will be randomized to receive placebo.
Each subject will receive only one dose of either AZD8108 or placebo on Day 1.
In Part 2 of the study (multiple ascending dose portion), approximately 24 subjects will be randomly assigned.
Eight (8) subjects will be randomized in each of 3 dosage-level cohorts.
Within each cohort, 6 subjects will be randomized to receive AZD8108 and 2 subjects will be randomized to receive placebo.
Each subject will receive twelve doses of either AZD8108 or placebo
Type d'étude
Interventionnel
Inscription (Réel)
258
Phase
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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New York
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New York, New York, États-Unis, 10019
- Clinilabs, Inc.
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 55 ans (Adulte)
Accepte les volontaires sains
Oui
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria: Inclusion Criteria: 1. Subjects must understand the nature of the study and must provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-specific procedures. 2. Men and postmenopausal or surgically sterile women age 18-55 years inclusive. 3. Subjects must have a body mass index (BMI) between 19 and 30, inclusive and weigh between 50kg and 100kg inclusive. 4.Subjects must be fluent in English.
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Exclusion Criteria:1. A history or presence of a clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, respiratory, immunologic, hematologic, dermatologic, or neurologic abnormality. 2. A clinically significant abnormality on physical examination, neurological examination, EEG, ECG, vital signs or laboratory evaluations at screen or between screen and dose administration. 3. A history of seizure. 4.A history of head trauma, including closed head injury with loss of consciousness. 5.Any history of suicide attempt or suicidal behavior, or, in the opinion of the investigator, clinically significant risk of suicide or violent behavior. 6. Urine drug screen positive for a drug of abuse 7. A family history of schizophrenia, schizoaffective disorder, or psychosis in first degree relatives.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Science basique
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: AZD8108
Subjects will participate in 1 of 7 groups and receive single or multiple doses of AZD8108 or matching placebo.
In each group 6 subjects will receive AZD8108
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Drug: AZD8108 Single or Multiple doses administered orally as a solution.
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Comparateur placebo: Placebo to match AZD8108
Subjects will participate in 1 of 7 groups and receive single or multiple doses of AZD8108 or matching placebo.
In each group 2 subjects will receive matching placebo
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Placebo to match AZD8108 Single or Multiple doses of matching placebo administered orally as a solution
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Safety Laboratory - Thyroid Stimulating Hormone Above Upper Limit of Normal
Délai: Day -1 to 7 days after last dose
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Safety Laboratory - Thyroid Stimulating Hormone participants with laboratory value above the upper limit of normal
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Day -1 to 7 days after last dose
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Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 After Single/1st Dose of AZD8108
Délai: Pre-dose,5,15,30 min, 1,1.5,2,3,4,6,8,10,12,14,16,24,48,(72 SAD only) hr after day 1 dose
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Pharmacokinetic : Area under the concentration curve (0 to infinity), AZD6765 after single/first dose of AZD8108
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Pre-dose,5,15,30 min, 1,1.5,2,3,4,6,8,10,12,14,16,24,48,(72 SAD only) hr after day 1 dose
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Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hour), AZD6765 MAD Day 6 Dose of AZD8108
Délai: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24 hr after Day 6 dose
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Pharmacokinetic : Area under the concentration curve (0 to 24 hour), AZD6765 MAD Day 6 dose of AZD8108 Cohort 5 & 7, Cohort 6 did not reach Day 6
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Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24 hr after Day 6 dose
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Pharmacokinetic :Area Under the Concentration Curve (0 to Infinity), AZD6765 MAD Day 12 Dose of AZD8108
Délai: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48, 72 hr after Day 12 dose
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Pharmacokinetic : Area under the concentration curve (0 to infinity), AZD6765 MAD Day 12 dose of AZD8108 Cohort 5 & 7, Cohort 6 did not reach Day 12
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Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48, 72 hr after Day 12 dose
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Pharmacokinetic :Area Under the Concentration Curve (0 to 24 Hours), AZD6765 After DAY 12 Dose of AZD8108
Délai: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16, and 24 hours after dose
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Pharmacokinetic : Area under the concentration curve (0 to 24 hours), AZD6765 after Day 12 dose of AZD8108 cohort 5 & 7, Cohort 6 dod not reach Day 12
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Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16, and 24 hours after dose
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Pharmacokinetic : Maximum Concentration of AZD6765 After Single/1st Dose of AZD8108
Délai: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,25,48,972 SAD only)hr after Day 1 dose
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Pharmacokinetic : Maximum concentration of AZD6765 after single/first dose of AZD8108
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Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,25,48,972 SAD only)hr after Day 1 dose
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Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 6 Dose of AZD8108
Délai: Pre-dose, 5,15.30 min, 1,1.5,2,3,4,6,8,10,12,16,24 hr after Day 6 dose
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Pharmacokinetic : Maximum concentration of AZD6765 after MAD Day 6 dose of AZD8108, Cohorts 5 & 7, Cohort 6 did not reach Day 6
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Pre-dose, 5,15.30 min, 1,1.5,2,3,4,6,8,10,12,16,24 hr after Day 6 dose
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Pharmacokinetic : Maximum Concentration of AZD6765 After MAD Day 12 Dose of AZD8108
Délai: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,72 hr after Day 12 dose
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Pharmacokinetic : Maximum concentration of AZD6765 after MAD Day 12 dose of AZD8108, Cohorts 5 & 7, Cohort 6 did not reach Day 12
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Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,72 hr after Day 12 dose
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Single (SAD)/ 1st (MAD) Dose of AZD8108
Délai: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,(72 SAD only) hr after day 1 dose
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Pharmacokinetic: Time to Maximum plasma concentration of AZD6765 after single (SAD) / first (MAD) dose AZD8108
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Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,(72 SAD only) hr after day 1 dose
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Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (SAD) After Single Dose of AZD8108
Délai: Collection 0-6, 6-12,12-24, 24-48, (48-72 SAD only) hy after Day 1 dose
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Pharmacokinetic: Fraction of equivalent dose of AZD6765 excreted in urine (SAD) after single dose of AZD8108 (Cohorts 1 - 3)
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Collection 0-6, 6-12,12-24, 24-48, (48-72 SAD only) hy after Day 1 dose
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Pharmacokinetic: Fraction of Equivalent Dose of AZD6765 Excreted in Urine (MAD) After Day 12 Dose of AZD8108
Délai: Collection 0-6, 0-12, 12-24, 24-48, 48-72 hr after Day 12 dose
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Pharmacokinetic: Fraction of equivalent dose of AZD6765 excreted in urine (MAD) after Day 12 dose of AZD8108 Cohorts 5 & 7, Cohort 6 did not reach day 12
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Collection 0-6, 0-12, 12-24, 24-48, 48-72 hr after Day 12 dose
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Pharmacokinetic: Time to Maximum Plasma Concentration of AZD6765 After Day 12 (MAD) Dose of AZD8108
Délai: Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,72 hours after Day 12 dose
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Pharmacokinetic: Time to Maximum plasma concentration of AZD6765 after Day 12 (MAD) dose AZD8108 Cohorts 5 & 7, Cohort 6 did not reach day 12
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Pre-dose, 5,15,30 min, 1,1.5,2,3,4,6,8,10,12,16,24,48,72 hours after Day 12 dose
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Pharmacokinetic: Accumulation Index for Area Under Concentration Curve (0 to 24 Hour) MAD
Délai: Day 12 compared to Day 1
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Pharmacokinetic: Accumulation index for Area Under Concentration Curve (0 to 24 hour) MAD Cohorts 5 & 7, cohort 6 did not reach day 12 [accumulation index (Day 6 or 12 /Day1)]
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Day 12 compared to Day 1
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
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EEG Parameter (DAY 1) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction
Délai: 8 hours after dose
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EEG parameter (DAY 1) - Gamma - Change from baseline in Total Area of the Brain (eyes closed) - to identify a dose related change in EEG gamma bands to assess target engagement, a consistent change in either direction relative to placebo would be of interest
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8 hours after dose
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EEG Parameter (DAY 6) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed)- Consistent Change in Either Direction
Délai: 8 hours after dose
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EEG parameter (DAY 6) - Gamma - Change from baseline in Total Area of the Brain (eyes closed) Cohort 5 & 7, Cohort 6 did not reach Day 6; to identify a dose related change in EEG gamma bands to assess target engagement, a consistent change in either direction compared to placebo was of interest
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8 hours after dose
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EEG Parameter (DAY 12) - Gamma - Change From Baseline in Total Area of the Brain (Eyes Closed) - Consistent Change in Either Direction
Délai: 8 hours after dose
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EEG parameter (DAY 12) - Gamma - Change from baseline in Total Area of the Brain (eyes closed) Cohort 5 & 7 , Cohort 6 did not reach Day 12; to identify a dose related change in EEG gamma bands to assess target engagement, a consistent change in either direction compared to placebo would be of interest
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8 hours after dose
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Mina Pastagia, MD, MS, Clinilabs, Inc.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 novembre 2014
Achèvement primaire (Réel)
1 septembre 2015
Achèvement de l'étude (Réel)
1 septembre 2015
Dates d'inscription aux études
Première soumission
23 septembre 2014
Première soumission répondant aux critères de contrôle qualité
24 septembre 2014
Première publication (Estimation)
25 septembre 2014
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
7 avril 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
9 mars 2017
Dernière vérification
1 mars 2017
Plus d'information
Termes liés à cette étude
Autres numéros d'identification d'étude
- D5800C00001
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