A Phase 1, Within Cohort, Randomized, Double Blind, Third-party Open, Placebo-controlled, Single- And Multiple Dose Escalation, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06700841 In Healthy Subjects And Subjects With Plaque Psoriasis And Bioavailability Of A Tablet Formulation Relative To Suspension Formulation And The Effect Of Food On A Tablet Formulation Of Pf-06700841
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Single Ascending Dose (SAD) Cohort: Change From Baseline in Blood Pressure at Day 1
研究概览
简要总结
The main purpose of the study is to determine if PF-06700841 is safe and well tolerated when administered to humans. A secondary purpose is to assess what the body does to PF-06700841 and to assess what PF-06700841 does to the body when given as single and multiple doses. The pharmacokinetic properties of different forms of PF-06700841 may be studied (tablet and solution/suspension forms).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Key Inclusion Criteria for Healthy Subject Cohorts:
- •Healthy male subjects and/or female subjects of non-childbearing potential between the ages of 18 and 55 years, inclusive
- •No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
- •Key Inclusion Criteria for Psoriasis Subject Cohorts:
- •Male subjects and/or female subjects of non-childbearing potential with a diagnosis of plaque psoriasis who are between the ages of 18 and 65 years, inclusive
- •Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose
排除标准
- •Key Exclusion Criteria for Healthy Subject Cohorts:
- •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 time of dosing)
- •Males of childbearing potential 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
- •Key Exclusion Criteria for Psoriasis Subject Cohorts:
- •Currently have non plaque forms of psoriasis, (eg, erythrodermic, guttate, or pustular psoriasis).
- •Have current drug induced psoriasis, eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium
- •Males of childbearing potential 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
研究组 & 干预措施
PF-06700841 Oral Solution/Suspension
干预措施: PF-06700841 oral solution/suspension (Drug)
PF-06700841 Tablet
干预措施: PF-06700841 tablet (Drug)
Placebo
Oral placebo comparator for the healthy subject single and multiple ascending dose periods, and the psoriasis multiple dose period. No placebo used for the bioavailability investigation.
干预措施: Placebo (Other)
结局指标
主要结局
Single Ascending Dose (SAD) Cohort: Change From Baseline in Blood Pressure at Day 1
时间窗: Baseline, 24 hours post-dose on Day 1
Single Ascending Dose (SAD) Cohort: Change From Baseline in Pulse Rate at Day 1
时间窗: Baseline, 24 hours post-dose on Day 1
Multiple Ascending Dose (MAD) Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 10
时间窗: Baseline, 16 hours post-dose on Day 10
Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Blood Pressure at Day 28
时间窗: Baseline, 16 hours post-dose on Day 28
Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Pulse Rate at Day 28
时间窗: Baseline, 16 hours post-dose on Day 28
Single Ascending Dose (SAD) Cohort: Change From Baseline in Heart Rate at Day 1
时间窗: Baseline, 24 hours post-dose on Day 1
Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Heart Rate at Day 10
时间窗: Baseline, 16 hours post-dose on Day 10
Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Heart Rate at Day 28
时间窗: Baseline, 16 hours post-dose on Day 28
Food Effect Cohort: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06700841
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Single Ascending Dose (SAD) Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 1
时间窗: Baseline, 24 hours post-dose on Day 1
Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Pulse Rate at Day 10
时间窗: Baseline, 16 hours post-dose on Day 10
Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Oral Temperature at Day 10
时间窗: Baseline, 16 hours post-dose on Day 10
Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) at Day 28
时间窗: Baseline, 16 hours post-dose on Day 28
Number of Adverse Events (AEs) According to Severity
时间窗: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 28, MAD Psoriasis Cohort: Baseline up to Day 56, Food Effect Cohort: Baseline up to Day 37
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs were classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.
Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Blood Pressure at Day 10
时间窗: Baseline, 16 hours post-dose on Day 10
Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Oral Temperature at Day 28
时间窗: Baseline, 16 hours post-dose on Day 28
Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Change From Baseline in Creatinine Clearance at Day 10
时间窗: Baseline, 16 hours post-dose on Day 10
Creatinine clearance is a measure of kidney function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time.
Food Effect Cohort: Maximum Observed Plasma Concentration (Cmax) of PF-06700841
时间窗: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1
Single Ascending Dose (SAD) Cohort: Change From Baseline in Oral Temperature at Day 1
时间窗: Baseline, 24 hours post-dose on Day 1
Number of Participants With Change From Baseline in Physical Examinations
时间窗: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 28, MAD Psoriasis Cohort: Baseline up to Day 56, Food Effect Cohort: Baseline up to Day 37
Physical examinations included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems.
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Discontinuation Due to AEs
时间窗: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 28, MAD Psoriasis Cohort: Baseline up to Day 56, Food Effect Cohort: Baseline up to Day 37
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is 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 end of study (up to Day 8 in SAD cohort, Day 28 in MAD cohort, Day 56 in MAD Psoriasis cohort, Day 37 in Food effect cohort), that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAE and non-SAE.
Single Ascending Dose (SAD) Cohort: Change From Baseline in Creatinine Clearance at Day 1
时间窗: Baseline, 24 hours post-dose on Day 1
Creatinine clearance is a measure of kidney function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time.
Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Creatinine Clearance at Day 28
时间窗: Baseline, 16 hours post-dose on Day 28
Creatinine clearance is a measure of kidney function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time.
Number of Participants With Laboratory Abnormalities
时间窗: SAD Cohort: Baseline up to Day 8, MAD Cohort: Baseline up to Day 28, MAD Psoriasis Cohort: Baseline up to Day 56, Food Effect Cohort: Baseline up to Day 37
Criteria for abnormality:hematology: hemoglobin, hematocrit, red blood cell count: less than(\<) 0.8\*lower limit of normal (LLN); mean corpuscular volume; mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration: \<0.9\*LLN,\>1.1\*upper limit of normal (ULN); platelets: \<0.5\*LLN,\>1.75\*ULN, white blood cell count: \<0.6\*LLN, \>1.5\*ULN; lymphocytes, total neutrophils: \<0.8\*LLN, \>1.2\*ULN; eosinophils, basophils, monocytes: \>1.2\*ULN; coagulation: activated partial thromboplastin time, prothrombin, prothrombin international ratio: \>1.1\*ULN; liver function: bilirubin: \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: \>3.0\*ULN; protein, albumin: \<0.8\*LLN\>\</0\>1.2\*ULN; renal function:blood urea nitrogen,creatinine: \>1.3\*ULN; uric acid: \>1.2\*ULN; electrolytes: sodium, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN,\>1.1\*ULN; urinalysis: pH\<4.5, \>8; glucose, protein, blood, ketones, urobilinogen, bilirubin, nitrite; Other(glucose: \<0.6\*LLN,\>1.5\*ULN)
Food Effect Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06700841
时间窗: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1
Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast).
次要结局
- Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06700841(MAD: pre-dose 0.5, 1, 2, 4, 6, 8, 12, 24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5,1,2,4,6,8,12,16,24 hours post dose on Day 28)
- Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Apparent Clearance (CL/F) of PF-06700841(SAD: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post-dose on Day 1; MAD: pre-dose 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours post-dose on Day 28)
- Single Ascending Dose (SAD) Cohort: Dose Normalized Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf[dn]) of PF-06700841(pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1)
- Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Peak-Trough Fluctuation (PTF) of PF-06700841(MAD: pre--dose 0.5, 1, 2, 4, 6, 8, 12, 24 hour post--dose on Day 10; MAD Psoriasis: pre--dose, 0.5,1,2,4,6,8,12,16,24 hours post-dose on Day 28)
- Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06700841(SAD: pre-dose, 0.5,1,2,4,6,8,12,16,24,36,48,72,96 hour post dose on Day 1; MAD: pre-dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5,1,2,4,6,8,12,16,24 hours post dose on Day 28)
- Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Plasma Decay Half-Life (t1/2) of PF-06700841(SAD: pre--dose, 0.5,1,2,4,6,8,12,16,24,36,48,72,96 hour post-dose on Day 1; MAD: pre--dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10; MAD Psoriasis: pre--dose, 0.5,1,2,4,6,8,12,16,24 hours post-dose on Day 28)
- Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Mean Residence Time (MRT) of PF-06700841(SAD: pre--dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post-dose on Day 1; MAD: pre--dose 0.5, 1, 2, 4, 6, 8, 12, 24 hour post--dose on Day 10; MAD Psoriasis: pre--dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours post-dose on Day 28)
- Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Maximum Observed Plasma Concentration (Cmax) of PF-06700841(SAD: pre-dose, 0.5,1,2,4,6,8,12,16,24,36,48,72,96 hour post dose on Day 1; MAD: pre-dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5,1,2,4,6,8,12,16,24 hours post dose on Day 28)
- Single Ascending Dose (SAD) Cohort: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06700841(pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1)
- Multiple Ascending Dose (MAD) Cohort: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau[dn]) of PF-06700841(pre-dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10)
- Multiple Ascending Dose (MAD) Cohort: Amount of PF-06700841 Recovered Unchanged in the Urine Over the Time Interval Tau (Aetau)(0-24 hour on Day 10)
- Multiple Ascending Dose (MAD) Cohort: Renal Clearance(0-24 hours on Day 10)
- Single Ascending Dose (SAD) Cohort: Interferon Gamma-induced Protein 10 (IP-10) Concentration in Serum at Baseline(Baseline)
- Food Effect Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF--06700841(Pre--dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 hours post dose on Day 1)
- Single Ascending Dose (SAD) Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06700841(pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1)
- Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06700841(SAD: pre-dose, 0.5,1,2,4,6,8,12,16,24,36,48,72,96 hour post dose on Day 1; MAD: pre-dose 0.5,1,2,4,6,8,12,24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5,1,2,4,6,8,12,16,24 hours post dose on Day 28)
- Single Ascending Dose (SAD) Cohort: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06700841(Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post dose on Day 1)
- Multiple Ascending Dose (MAD) Cohort: Percentage of Dose of PF-06700841 Recovered Unchanged in the Urine Over the Time Interval Tau (Aetau%)(0-24 hours on Day 10)
- Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Interferon Gamma-induced Protein 10 (IP-10) Concentration in Serum at Day 2, 5, 10, 11, 28(Baseline, Day 2, 5, 10, 11, 28)
- Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Reticulocyte Counts at Day 4, 6, 8, 10, 13, 14, 21, 28, 35, 42 and 56(Baseline, Day 4, 6 ,8,10, 13, 14, 21, 28, 35, 42, 56)
- Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) and MAD Psoriasis Cohort: Apparent Volume of Distribution (Vz/F) of PF-06700841(SAD: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hour post-dose on Day 1; MAD: pre-dose 0.5, 1, 2, 4, 6, 8, 12, 24 hour post-dose on Day 10; MAD Psoriasis: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours post-dose on Day 28)
- Single Ascending Dose (SAD) Cohort: High Sensitivity C-reactive Protein (hsCRP) Concentration in Serum at Baseline(Baseline)
- Single Ascending Dose (SAD) Cohort: Change From Baseline in Neutrophil Counts at Day 2, 5 and 8(Baseline, Day 2, 5, 8)
- Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Neutrophil Counts at Day 4, 6, 8, 10, 13, 14, 21, 28, 35, 42 and 56(Baseline, Day 4, 6 ,8,10, 13, 14, 21, 28, 35, 42, 56)
- Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline in Interferon Gamma-Induced Protein 10 (IP-10) Concentration in Serum at Day 2, 5, 7, 14, 21, 28, 29, 35, 56(Baseline, Day 2, 5, 7, 14, 21, 28, 29, 35, 56)
- Multiple Ascending Dose (MAD) Cohort: Change From Baseline In High Sensitivity C-reactive Protein (hsCRP) at Day 2, 5, 10, 11, 28(Baseline, Day 2, 5, 10, 11, 28)
- Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Neutrophil Counts at Day 4, 8, 10, 11, 14, 28(Baseline, Day 4, 8, 10, 11, 14, 28)
- Single Ascending Dose (SAD) Cohort: Change From Baseline in Reticulocyte Counts at Day 2, 5, 8(Baseline, Day 2, 5, 8)
- Multiple Ascending Dose (MAD) Psoriasis Cohort: Change From Baseline In High Sensitivity C-reactive Protein (hsCRP) at Day 2, 5, 7, 14, 21, 28, 29, 35 and 56(Baseline, Day 2, 5 ,7,14, 21, 28, 29, 35, 56)
- Multiple Ascending Dose (MAD) Cohort: Change From Baseline in Reticulocyte Counts at Day 4, 8, 10, 11, 14 and 28(Baseline, Day 4, 8, 10, 11, 14, 28)