First-In-Human Study Of Single And Multiple Ascending Doses Of PF-06751979
22 de febrero de 2018 actualizado por: Pfizer
A Phase 1, Randomized, Double-blind, Sponsor-open, Placebo Controlled First-in-human Trial To Evaluate The Safety,Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06751979 After Oral Administration Of Single And Multiple Ascending Doses To Healthy Adult And Elderly Subjects
The purpose of this study is to evaluate the safety, tolerability, PK and PD of PF-06751979 following oral doses in healthy adult and healthy elderly subjects.
Descripción general del estudio
Estado
Terminado
Condiciones
Tipo de estudio
Intervencionista
Inscripción (Actual)
55
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
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California
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Glendale, California, Estados Unidos, 91206
- Glendale Adventist Medical Center
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Glendale, California, Estados Unidos, 91206
- California Clinical Trials Medical Group, Inc
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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 85 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years or between the ages of 60 and 85 years, inclusive.
- Body Mass Index (BMI) of 17.5 to 32 kg/m2; and a total body weight >50 kg (110 lbs) at Screening.
- Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study.
Exclusion Criteria:
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
- Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.
- Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
- Any severe acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
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
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Single Ascending Dose Cross-over
Single Ascending Dose in 4-way cross-over design (PF-06751979/Placebo).
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PF-06751979 administered as a single dose (solution/suspension) in cross-over fashion.
Each subject may receive up to 4 study treatments (placebo and up to 3 doses of PF-06751979).
The dose levels are 3 mg, 12 mg, 40 mg, 160 mg.
Matched Placebo solution/suspension administered as single dose.
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Experimental: Multiple Ascending Dose PF-06751979
Multiple dose administration to Healthy Subjects in parallel cohorts(PF-06751979)
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PF-06751979 (solution/suspension) administered daily for 14 consecutive days to parallel cohorts.
The dose levels are 5 mg, 15 mg, 50 mg.
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Comparador de placebos: Multiple Ascending Dose Placebo
Multiple dose administration to Healthy Subjects in parallel cohorts(Placebo)
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Matched Placebo (solution/suspension)administered daily for 14 consecutive days.
PF-06751979 (solution/suspension) administered daily for 14 consecutive days.
The dose level is 50 mg.
Matched Placebo (suspension/solution) administered daily for 14 consecutive days to parallel cohorts.
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Experimental: Multiple Dose Elderly PF-06751979
Multiple dose administration to Healthy Elderly Subjects (PF-06751979)
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PF-06751979 (solution/suspension) administered daily for 14 consecutive days.
The dose level is 50 mg.
Matched Placebo (suspension/solution) administered daily for 14 consecutive days to parallel cohorts.
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Comparador de placebos: Multiple Dose Elderly Placebo
Multiple dose administration to Healthy Elderly Subjects (Placebo)
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Matched Placebo (solution/suspension)administered daily for 14 consecutive days.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Periodo de tiempo: Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Treatment-emergent were events between first dose of study drug up to the follow up visit (up to 47 days in Part A, 29 days in Part B and C), that were absent before treatment or that worsened relative to pretreatment state.
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Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days
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Number of Participants With Abnormal Physical Examinations Findings
Periodo de tiempo: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems.
Abnormality in physical examinations was based on investigator's discretion.
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Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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Number of Participants With Abnormal Neurological Examinations Findings
Periodo de tiempo: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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The neurological examination included the assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait.
Abnormality in neurological examinations was based on investigator's discretion.
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Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline
Periodo de tiempo: Baseline
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C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior.
C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent).
In this outcome measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at baseline were reported.
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Baseline
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Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7
Periodo de tiempo: Day 7
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C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior.
C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent).
In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at day 7 were reported.
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Day 7
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Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14
Periodo de tiempo: Day 14
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C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior.
C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent).
In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at Day 14 were reported.
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Day 14
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Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19
Periodo de tiempo: Day 19
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C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior.
C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent).
In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at Day 19 were reported.
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Day 19
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Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Periodo de tiempo: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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Criteria for clinically significant ECG abnormalities: maximum PR interval >=300 milliseconds (msec) and maximum PR interval increase from baseline (IFB): percent change (Pctchg) >=25 percent (%) for baseline value of >200 msec and Pctchg>=50% for baseline value of <=200 msec for PR interval, maximum QRS interval >=140 msec and a maximum IFB: Pctchg>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to <480 msec, 480 msec to <500 msec or >=500 msec and a maximum change of <=30 change <60 or >=60 msec from baseline.
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Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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Number of Participants With Laboratory Abnormalities
Periodo de tiempo: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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Abnormalities criteria:hematology(hemoglobin; hematocrit; RBC<0.8*lower
limit of normal [LLN]; platelets<0.5*LLN,>1.75*upper
limit of normal [ULN]; WBC<0.6*LLN,>1.5*ULN;
lymphocytes; neutrophils; basophils; eosinophils; monocytes<0.8*LLN,>1.2*ULN;
coagulation(prothrombin (PT); PT ratio>1.1*ULN),
liver(bilirubin>1.5*ULN;
aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase; gamma GT>0.3*ULN; protein; albumin<0.8*LLN,>1.2*ULN);
renal(blood urea nitrogen, creatinine>1.3*ULN;
uric acid>1.2*ULN);
electrolytes(sodium<0.95*LLN,>1.05*ULN;
potassium; chloride; calcium; bicarbonate<0.9*LLN,>1.1*ULN),
chemistry(glucose<0.6*LLN,>1.5*
ULN); urinalysis(pH <4.5,>8; glucose, ketones, protein, blood, urobilinogen, nitrite, bilirubin, leukocyte, esterase>1; WBC; bacteria>=20, epithelial cells>=6; granular casts, hyaline casts, red cell casts, white cell casts>1; lipids(cholesterol[C], LDL-C>1.3*ULN;
HDL-C<0.8*LLN,
triglycerides>1.3*ULN);
hormones(T4, T3, T4, TSH<0.8*LLN,>1.2*ULN)
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Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Periodo de tiempo: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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Following parameters were analyzed for examination of vital signs: supine systolic and diastolic blood pressure, pulse rate and body temperature.
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Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry
Periodo de tiempo: Day 1
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Continuous cardiac telemetry was conducted in participants.
All abnormal cardiac rhythms were recorded and reviewed by the study physician for the presence of rhythms of potential clinical concern.
In this outcome measure, number of participants who had cardiac rhythms of potential clinical concern (based on physician's discretion) were reported.
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Day 1
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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AUClast is the area under the plasma concentration time-curve from time zero to the time of last quantifiable concentration.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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AUClast(dn) was calculated by dividing AUClast by the exact dose of PF-06751979 (in mg) administered.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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AUCinf(dn) was calculated by dividing AUCinf by the exact dose of PF-06751979 (in mg) administered.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Plasma Decay Half-Life (t1/2) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Apparent Oral Clearance (CL/F) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Drug clearance is the quantitative measure of the rate at which a drug substance is removed from the blood.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
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Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
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Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
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Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part B: Apparent Oral Clearance (CL/F) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
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Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours.
AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
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Part B: Peak-to-Trough Ratio (PTR) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 14
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Rac for AUCtau for Day 7 was calculated as: AUCtau on Day 7 divided by AUCtau on Day 1. Rac for AUCtau for Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 14
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Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Rac for Cmax for Day 7 was calculated as: Cmax on Day 7 divided by Cmax on Day 1. Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
Periodo de tiempo: 0-24 hours on Day 14
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Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours.
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0-24 hours on Day 14
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Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
Periodo de tiempo: 0-24 hours on Day 14
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Aetau% was calculated as: 100*Aetau/dose.
Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours.
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0-24 hours on Day 14
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Part B: Renal Clearance of PF-06751979
Periodo de tiempo: 0-24 hours on Day 14
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Renal clearance was calculated as amount of drug excreted unchanged in urine during the dosing interval tau (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours.
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0-24 hours on Day 14
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Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14
Periodo de tiempo: Baseline, Day 14
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ABeta is the peptide fragment of the amyloid precursor protein.
Percent change from baseline in CSF concentration of ABeta fragments (ABeta x-40, ABeta 1-40 and ABeta total) at Day 14 was reported in this outcome measure.
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Baseline, Day 14
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Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hour post dose on Day 14
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Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hour post dose on Day 14
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Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
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Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours.
AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
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Part C: Apparent Oral Clearance (CL/F) of PF-06751979 on Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 on Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part C: Peak-to-Trough Ratio (PTR) of PF-06751979 at Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
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Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Rac for AUCtau at Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1, where Cmax was the maximum observed plasma concentration.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF 06751979 at Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14
Periodo de tiempo: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
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predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
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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)
1 de julio de 2015
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
22 de julio de 2015
Primero enviado que cumplió con los criterios de control de calidad
23 de julio de 2015
Publicado por primera vez (Estimar)
27 de julio de 2015
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
1 de noviembre de 2018
Última actualización enviada que cumplió con los criterios de control de calidad
22 de febrero de 2018
Última verificación
1 de febrero de 2018
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- B8271001
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 PF-06751979 single ascending dose
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