A PHASE 1, RANDOMIZED, CROSSOVER DESIGN STUDY TO ASSESS PALATABILITY OF OSIVELOTOR (PF-07940367) PEDIATRIC FORMULATIONS WITH DOSING VEHICLE (PART 1) AND RANDOMIZED, SINGLE-DOSE, PARALLEL DESIGN STUDY TO ESTIMATE RELATIVE BIOAVAILABILITY OF OSIVELOTOR PEDIATRIC FORMULATION WITH DOSING VEHICLE AND WITH WATER COMPARED TO CLINICAL TABLET FORMULATION, AND EFFECT OF FOOD AND/OR ACID-REDUCING AGENT ON BIOAVAILABILITY IN HEALTHY ADULT PARTICIPANTS (PART 2)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- Pfizer
- 入组人数
- 52
- 主要终点
- Part 1: Mouth Feel Effect
研究概览
简要总结
A study to learn how different preparations of osivelotor taste and enter the blood with food or liquids, or with an antacid in healthy adults.
详细描述
This study has two parts: Part 1 and Part 2. The purpose of Part 1 of this study is to learn how different preparations of the study medicine called osivelotor (PF-07940367) taste. The purpose of Part 2 of this study is to learn how the study medicine is taken up into the blood when mixed with:
- soft foods or liquids given on an empty stomach or
- with an acid-reducing agent in healthy adults.
This study is seeking participants who are:
- healthy females and males of 18 to 65 years of age.
- have a body mass index of 16 to 32 kilogram per meter squared.
- have a total body weight of more than 50 kilograms (110 pounds).
Participants in Part 1 of the study will receive the study medicine 4 times with at least 2-hour interval on day one. This study medicine will not be swallowed but will be placed in the mouth and spat out. The participants will then complete a short questionnaire 4 times over 20 minutes. All study medicines will be given in the study clinic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- None
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
- •Male and female participants aged 18 years (or the minimum age of consent in accordance with local regulations if >18 years) to 65 years (inclusive) at screening who are overtly healthy as determined by medical evaluation including a detailed medical history, complete physical examination (PE), including blood pressure (BP) and pulse rate (PR) measurement, 12-lead ECG (electrocardiogram) and clinical laboratory tests.
- •Body mass index (BMI) of ≥16 to ≤32 kg/m2; 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).
- •Use of prescription or nonprescription drug, dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer), with the exception of moderate or strong cytochrome P450 (CYP)3A inducers or inhibitors which are prohibited within 14 days plus 5 half-lives, prior to the first dose of study intervention.
- •Current use of any prohibited concomitant medication(s) or participant unwilling/able to use a permitted concomitant medication(s).
- •Previous administration with an investigational product (drug or vaccine) 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). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study.
- •For females, pregnancy, as indicated by a positive serum pregnancy test (serum) at screening and/or a positive pregnancy test (serum and/or urine) on Day -1 in women of childbearing potential.
- •Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants <60 years; and ≥150/90 mm/Hg for participants ≥60 years old, following at least 5 minutes of supine rest.
- •Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF [QTc corrected using Fridericia's formula] >450 ms, complete left bundle branch block (LBBB), signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third- degree AV (atrioventricular) block, or serious bradyarrhythmias or tachyarrhythmias).
- •Participants with defined abnormalities in kidney and liver laboratory tests at screening.
- •Participants in Sub-Saharan Africa or who have relocated from Sub-Saharan Africa within 6 months of screening.
研究组 & 干预措施
Part 1 Sequence 4 - Palatability
Participants will receive 4 preparations (Treatments D, A, B, C) of osivelotor pellet/granules at least 2 hours apart on Day 1 which they will put in their mouth and then spit it out.
干预措施: Osivelotor (Drug)
Part 1 Sequence 3 - Palatability
Participants will receive 4 preparations (Treatments C, D, A, B) of osivelotor pellet/granules at least 2 hours apart on Day 1 which they will put in their mouth and then spit it out.
干预措施: Osivelotor (Drug)
Part 2 Pharmacokinetics - Treatment F
Participants will receive 1 preparation (Treatment F) of osivelotor pellet/granules on Day 1 which they will put in their mouth and swallow. They might have a dose on Day 7 which they will put in their mouth and then spit it out; afterwards they will complete the taste questionnaire.
干预措施: Osivelotor (Drug)
Part 1 Sequence 2 - Palatability
Participants will receive 4 preparations (Treatments B, C, D, A) of osivelotor pellet/granules at least 2 hours apart on Day 1 which they will put in their mouth and then spit it out.
干预措施: Osivelotor (Drug)
Part 2 Pharmacokinetics - Treatment H
Participants will receive famotidine and afterwards preparation (Treatment H) of osivelotor pellet/granules on Day 1 which they will put in their mouth and swallow.
干预措施: Osivelotor (Drug)
Part 2 Pharmacokinetics - Treatment K
Participants will receive 1 preparation (Treatment K) of osivelotor pellet/granules on Day 1 which they will put in their mouth and swallow.
干预措施: Osivelotor (Drug)
Part 2 Pharmacokinetics - Treatment H
Participants will receive famotidine and afterwards preparation (Treatment H) of osivelotor pellet/granules on Day 1 which they will put in their mouth and swallow.
干预措施: Famotidine (Other)
Part 2 Pharmacokinetics - Treatment I
Participants will receive 1 preparation (Treatment I) of osivelotor pellet/granules on Day 1 which they will put in their mouth and swallow.
干预措施: Osivelotor (Drug)
Part 2 Pharmacokinetics - Treatment J
Participants will receive 1 preparation (Treatment J) of osivelotor pellet/granules on Day 1 which they will put in their mouth and swallow. They might have a dose on Day 7 which they will put in their mouth and then spit it out; afterwards they will complete the taste questionnaire.
干预措施: Osivelotor (Drug)
Part 1 Sequence 1 - Palatability
Participants will receive 4 preparations (Treatments A, B, C, D) of osivelotor pellet/granules at least 2 hours apart on Day 1 which they will put in their mouth and then spit it out.
干预措施: Osivelotor (Drug)
Part 2 Pharmacokinetics - Treatment E
Participants will receive 1 preparation (Treatment E) of osivelotor pellet/granules on Day 1 which they will put in their mouth and swallow.
干预措施: Osivelotor (Drug)
Part 2 Pharmacokinetics - Treatment G
Participants will receive 1 preparation (Treatment G) of osivelotor pellet/granules on Day 1 which they will put in their mouth and swallow.
干预措施: Osivelotor (Drug)
结局指标
主要结局
Part 1: Mouth Feel Effect
时间窗: 1, 5, 10, 20 minutes post dose
Mouth feel visual analogue scale (VAS) assesses the participant's global perception of mouth feel (that is, effects over the whole course of the drug experience including any carryover effects). A 100-point VAS is used to assess response based on a score ranging from 0 points to 100 points (0 points = " Bad Mouth feel ", 50 points = "neither bad nor good mouth feel", and 100 points = "Good Mouth feel ").
Part 1: Tongue/mouth burn effect
时间窗: 1, 5, 10, 20 minutes post dose
Tongue/mouth burn visual analogue scale (VAS) assesses the participant's global perception of tongue/mouth burn (that is, effects over the whole course of the drug experience including any carryover effects). A 100-point VAS is used to assess response based on a score ranging from 0 points to 100 points (0 points = "extreme burn", 50 points = "neither bad nor good burn", and 100 points = "no burn").
Part 2: Area under the Concentration-Time Curve (AUC 0-144) of osivelotor, as data permits
时间窗: 0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
AUC from 0 to 144 hours is a measure of the whole blood concentration of the drug over time. It is used to characterize drug absorption; if AUC0-144 not available, then AUClast will be calculated.
Part 1: Bitter effect
时间窗: 1, 5, 10, 20 minutes post dose
Bitter visual analogue scale (VAS) assesses the participant's global perception of bitterness (that is, effects over the whole course of the drug experience including any carryover effects). A 100-point VAS is used to assess response based on a score ranging from 0 points to 100 points (0 points = " extremely bitter ", 50 points = "neither bad nor good bitterness", and 100 points = "not bitter").
Part 1:Overall liking effect
时间窗: 1, 5, 10, 20 minutes post dose
Overall liking visual analogue scale (VAS) assesses the participant's global perception of overall liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100-point VAS is used to assess response based on a score ranging from 0 points to 100 points (0 points = "bad", 50 points = "neither bad nor good", and 100 points = "good").
Part 1: Overall liking effect
时间窗: 1, 5, 10, 20 minutes post dose
Overall liking visual analogue scale (VAS) assesses the participant's global perception of overall liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100-point VAS is used to assess response based on a score ranging from 0 points to 100 points (0 points = "bad", 50 points = "neither bad nor good", and 100 points = "good").
Part 2: Area under the Concentration-Time Curve (AUC 0-144) (if data permit, otherwise AUClast) for osivelotor in whole blood.
时间窗: 0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
AUC from 0 to 144 hours is a measure of the whole blood concentration of the drug over time. It is used to characterize drug absorption; if AUC0-144 not available, then AUClast will be calculated.
Part 2: Maximum observed whole blood concentration (Cmax) for osivelotor pediatric formulation in whole blood
时间窗: 0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose
Cmax is a measure of the highest whole blood concentration of the drug over time.
次要结局
- Part 2: Number of Participants With Treatment-Emergent Adverse Events (AEs)(Day 1 to 84)
- Part 2: Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings(Day 1 and Day 7)
- Part 2: Number of Participants With Clinically Significant With Clinically Significant Vital Signs(Day 1, 2 and Day 7)
- Part 2: Maximum observed whole blood concentration (Cmax) of osivelotor pediatric formulation(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 1: Number of Participants With Treatment-Emergent Adverse Events (AEs)(Day 1 to 28)
- Part 1 and 2: Number of participants with clinically significant laboratory abnormalities.(Day 1 to Day 2 for Part 1, Day 1 to Day 7 for Part 2.)
- Part 1: Number of Participants With Clinically Significant With Clinically Significant Vital Signs(Day 1 and Day 2)
- Part 2: Area under the Concentration-Time Curve (AUC last) of osivelotor(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 1: Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings(Day 1 and Day 2)
- Part 2: Time (Tmax) to maximum observed whole blood concentration (Cmax) of osivelotor pediatric formulation(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 2: Maximum observed whole blood concentration (Cmax, dose normalized, if applicable) of osivelotor pediatric formulation(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 2: Area under the Concentration-Time Curve (AUC last, dose normalized, if applicable) of osivelotor(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 2: Number of Participants With Changes in Vital Signs(Day 1, 2 and Day 7)
- Part 1: Number of Participants With Changes in Vital Signs(Day 1 and Day 2)
- Part 1: Number of participants With Changes in laboratory assessments.(Day 1 to Day 2 for Part 1)
- Part 2: Number of participants With Changes in laboratory assessments.(Day 1 to Day 7 for Part 2.)
- Part 1: Number of Participants With Changes in Electrocardiograms (ECGs)(Day 1 and Day 2)
- Part 2: Number of Participants With Changes in Electrocardiograms (ECGs)(Day 1 and Day 7)
- Part 2: Area under the Concentration-Time Curve (AUC last) for osivelotor pediatric formulation in whole blood.(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 2: Maximum observed whole blood concentration (Cmax, dose normalized, if applicable) for osivelotor pediatric formulation in whole blood(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 2: Area under the Concentration-Time Curve (AUC last, dose normalized, if applicable) for osivelotor pediatric formulation in whole blood(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 2: Area under the Concentration-Time Curve (AUC0-144, dose normalized, if applicable) for osivelotor pediatric formulation in whole blood(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)
- Part 2: Time (Tmax) to maximum observed whole blood concentration (Cmax) for osivelotor pediatric formulation in whole blood(0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose)