A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, FIRST-IN-HUMAN STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE ASCENDING ORAL DOSES OF PF-07258669 ADMINISTERED TO HEALTHY ADULT PARTICIPANTS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This study will be the first time PF-07258669 is administered to humans. The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of PF-07258669 following administration of single oral doses to healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Female participants of non-child bearing potential and male participants and who are overtly healthy as determined by medical evaluation including medical history, physical examination, neurological examination, laboratory tests, and cardiac monitoring.
- •Participants who are willing to avoid direct sunlight exposure or any high intensity ultraviolet light exposure from admission to the follow-up contact and to apply sunscreen/lotion with a high sun protection factor, as appropriate.
- •BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing), as well as presence of lipid panel abnormalities (eg, hypercholesterolemia, hypertriglyceridemia).
- •Evidence of history of orthostatic hypotension or symptomatic bradycardia.
- •Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
- •Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
- •Current findings or documented past history of blood pressure values <90 mmHg systolic or <50 mmHg diastolic.
- •Any lipid panel parameter (ie, total cholesterol, triglycerides, HDL, and/or LDL) ≥1.25× ULN.
研究组 & 干预措施
Cohort 1
Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.
干预措施: PF-07258669 (Drug)
Cohort 1
Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.
干预措施: Placebo (Drug)
Cohort 2
Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.
干预措施: PF-07258669 (Drug)
Cohort 2
Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.
干预措施: Placebo (Drug)
Cohort 3
Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.
干预措施: PF-07258669 (Drug)
Cohort 3
Single dose administration of PF-07258669 and placebo; Within a cohort, participants will receive 3 doses of PF-07258669 and 1 dose of placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: From first dose of study intervention (Day 1) to telephone Follow Up (28-35 days after lase dose of study intervention) (approximately up to 20 weeks)
An adverse event (AE) was any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.
Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality)
时间窗: From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion.
Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria
时间窗: From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Abnormality in change from BL in vital signs included: standing diastolic blood pressure (BP) increase and decrease from BL of \>=20mmHg, standing systolic BP increase and decrease from BL of \>=30mmHg, supine diastolic BP increase and decrease from BL of \>=20mmHg, supine systolic BP increase and decrease from BL of \>=30mmHg.
Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria
时间窗: From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
ECG assessments inlcuded PR, QT, QTcF intervals and QRS complex. ECG abnormalities in change from BL included: PR interval BL \>200msec and max \>=25% increase from BL, or BL \<=200msec and max \>=50% increase from BL, QRS interval percent change from BL \>=50%, QTcF change from BL \>=30 and \<=60msec, or change from BL \>60msec.
Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings
时间窗: From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
The neurological exam consisted of assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait, to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator (or designee).
次要结局
- Maximum Observed Concentration (Cmax) of PF-07258669(At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4)
- Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669(At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4)
- Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669(At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4)
- Time for Cmax (Tmax) of PF-07258669(At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4)
- Terminal Half-life (t1/2) of PF-07258669(At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4)