A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE AND MULTIPLE-DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-07612577 (PF-06264006 [CTB] + PF-07338233 [AVP]) IN HEALTHY ADULT PARTICIPANTS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1
研究概览
简要总结
The purpose of this clinical trial is to learn about the pharmacokinetics, safety and tolerability of various single- and multiple-doses of CTB+AVP in healthy adult participants. CTB+AVP is a study medicine that is being developed to treat people with complicated urinary tract infections.
This study is seeking healthy adult male and female participants, 18-60 years of age, with a body weight > 50 kg and a BMI of 17.5 to 30.5 kg/m2.
Participants in Part-1 of the study will receive increasing single doses of CTB and/or AVP. Participants in Part-2 will receive increasing multiple doses of CTB+AVP three times a day for 7 days. The study team will monitor how each participant is doing with the study treatments via close monitoring in an in-patient setting. Experiences of people receiving CTB+AVP will be compared to those of people who do not. This will help determine if CTB+AVP is safe and well-tolerated at each dose of the study medicine.
Participants will take part in this study for a maximum of 12 weeks for Part-1 (up to 4 weeks for screening, up to 3 weeks of taking study medicine and up to 5 weeks for safety follow-up visit) and for a maximum of 10 weeks for Part-2 (up to 4 weeks for screening, up to 1 week of taking study medicine and up to 5 weeks for safety follow-up visit). During the duration of the study, blood samples for study medicine levels, and various measures for monitoring safety such as blood samples for clinical laboratory measurements, electrocardiograms and vital sign measurements will be taken.
详细描述
This is a 2-part study in healthy male and female adult participants.
Part-1 is to evaluate safety, tolerability and pharmacokinetics (PK) of 3 planned and 2 optional doses in 8 participants, in a 5-period sequential single dose design.
Part-2 is to evaluate safety, tolerability and PK of 1 planned and 2 optional cohorts in 8 participants each, in a multiple dose sequential design, with 7 days of repeated every 8 hours (q8h) dosing in each cohort. In addition, 2 optional cohorts in 6 participants each of Japanese descent and Chinese descent will also receive multiple doses of CTB+AVP repeated every 8 hours (q8h) for 7 days.
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)
盲法说明
Participant and investigator-blinded and sponsor-open design for Part-1 and Part-2.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)
- •For optional Japanese cohort only: Japanese participants who have 4 Japanese biologic grandparents who were born in Japan
- •For optional Chinese cohort only: Chinese participants who were born in mainland China, and both parents are of Chinese descent.
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)
- •Known allergy to the cephalosporin group of antibiotics
- •History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed
- •Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality [or other conditions or situations related to COVID-19 pandemic (eg, Contact with positive case, residence, or travel to an area with high incidence)] that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
- •A positive urine drug test
- •Positive test result for SARS-CoV-2 infection at the time of screening or Day -1
研究组 & 干预措施
Placebo
Part-1: Dose 1-5 Part-2: Cohort 2-4
干预措施: Placebo (Drug)
PF-06264006
Part-1: Dose 3, Dose 5
干预措施: PF-06264006 (Drug)
PF-07612577
Part-1: Dose 1, Dose 2, Dose 4, Dose 5 Part-2: Cohort 2-5
干预措施: PF-07612577 (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Time for Cmax (Tmax) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUClast was determined using the linear/log trapezoidal method.
Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-normalized Cmax was determined as Cmax/Dose.
Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUClast(dn) was determined as AUClast/Dose.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUCinf was calculated as AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUCinf(dn) was calculated as AUCinf/Dose.
Terminal Half-Life (t1/2) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Volume of Distribution (Vz/F) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Vz/F was calculated as Dose/(AUCinf \* kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Clearance (CL/F) of CTB: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
CL/F was calculated as Dose/AUCinf.
Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
The lower limit of quantification for AVP was 1.0 ng/mL.
Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUClast(dn) was determined as AUClast/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
The lower limit of quantification for AVP was 1.0 ng/mL.
Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of AVP, AVI and HPA: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUClast was determined using the linear/log trapezoidal method. The lower limit of quantification for AVP was 1.0 ng/mL.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUCinf was calculated as AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
AUCinf(dn) was calculated as AUCinf/Dose.
Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Vz/F was calculated as Dose/(AUCinf \* kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
CL/F was calculated as Dose/AUCinf.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1
时间窗: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention. Severe TEAEs were defined as type of AE that interrupted usual activities of daily life (ADL), or significantly affects clinical status, or may require intensive therapeutic intervention. Related TEAEs are defined as all TEAEs considered by the investigator to have at least a 'possible' relationship with the study intervention.
Number of Participants With Withdrawals Due to TEAEs: Part 1
时间窗: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention.
Number of Participants With Laboratory Test Abnormalities: Part 1
时间窗: Up to 24 hours post-dose
The laboratory abnormalities with non-zero participants were reported and it included: monocytes or leukocytes (greater than \[\>\] 1.2\* upper limit of normal \[ULN\]), urine hemoglobin scalar (greater than or equal to \[\>=1\]) and leukocyte esterase scalar (\>=1).
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1
时间窗: Up to 24 hours post-dose
Vital signs included blood pressure and pulse rate and were measured in a supine position after approximately 5 minutes of rest for the participant. Clinically significant changes in vital signs were determined by the investigator.
Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1
时间窗: Up to 24 hours post-dose
Twelve lead ECGs were collected using an ECG machine that automatically calculated heart rate and measured PR interval, QRS duration, QT interval, QT interval correct by Bazzette's formula (QTcB) and QT interval correct by Frederica formula QTcF. ECG abnormalities included: PR interval aggregate (millisecond \[msec\], maximum \[max.\] \>=300; baseline \> 200 and max. increase \>= 25 percent (%); baseline \> 200 and max. increase \>= 25%), QRS duration aggregate (msec, max \>=140; max. increase \>= 50%), QT interval aggregate (msec, value \> 500), QTCB interval aggregate and QTCF interval aggregate (msec, 450 \< max \<= 480; 480 \< max. \<= 500; max. \> 500; 30 \< max. increase \<= 60; max. increase \> 60).
Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of Cis-CTB and Trans-CTB: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-normalized Cmax was determined as Cmax/Dose.
Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Vz/F was calculated as Dose/(AUCinf \* kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
CL/F was calculated as Dose/AUCinf.
Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
The lower limit of quantification for AVP was 1.0 ng/mL.
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
The lower limit of quantification for AVP was 1.0 ng/mL.
Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for three times daily (TID) dosing.
Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on day 7
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The lower limit of quantification for HPA was 10.0 ng/mL.
Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Vz/F was calculated as Dose/(AUCinf \* kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The lower limit of quantification for AVI and HPA was 10.0 ng/mL.
Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2
时间窗: pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
CL/F was calculated as Dose/AUCinf.
Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2
时间窗: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were are any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention. Severe TEAEs were defined as type of AE that interrupted usual ADL, or significantly affects clinical status, or may require intensive therapeutic intervention. Related TEAEs are defined as all TEAEs considered by the investigator to have at least a 'possible' relationship with the study intervention.
Number of Participants With Withdrawals Due to TEAEs: Part 2
时间窗: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention.
Number of Participants With Laboratory Test Abnormalities: Part 2
时间窗: From start of treatment up to Day 7
The laboratory abnormalities with non-zero participants were reported and it included: neutrophils/ leukocytes (less than \[\<\] 0.8x lower limit of normal \[LLN\]), eosinophils/leukocytes (\>1.2x ULN), monocytes/leukocytes (\>1.2x ULN), bicarbonate (\>1.1x ULN), urine glucose (\>=1), ketones scalar (\>=1), urine hemoglobin scalar (\>=1), leukocyte esterase scalar (\>=1).
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2
时间窗: From start of treatment up to Day 7
Vital signs included blood pressure and pulse rate and were measured in a supine position after approximately 5 minutes of rest for the participant. Clinically significant changes in vital signs were determined by the investigator.
Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2
时间窗: From start of treatment up to Day 7
Twelve lead ECGs were collected using an ECG machine that automatically calculated heart rate and measured PR interval, QRS duration, QT interval, QT interval correct by Bazzette's formula (QTcB) and QT interval correct by Frederica formula QTcF. ECG abnormalities included: PR interval aggregate (millisecond \[msec\], maximum \[max.\] \>=300; baseline \> 200 and max. increase \>= 25 percent (%); baseline \> 200 and max. increase \>= 25%), QRS duration aggregate (msec, max \>=140; max. increase \>= 50%), QT interval aggregate (msec, value \> 500), QTCB interval aggregate and QTCF interval aggregate (msec, 450 \< max \<= 480; 480 \< max. \<= 500; max. \> 500; 30 \< max. increase \<= 60; max. increase \> 60).
次要结局
- Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2(anytime between 0 to 8 hours post dose on Day 6)
- Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2(anytime between 0 to 8 hours post dose on Day 6)
- Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2(anytime between 0 to 8 hours post dose on Day 6)
- Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2(pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7)
- Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2(pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7)
- Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2(pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7)
- Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2(pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7)
- Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2(pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 7)
- Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2(pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7)
- Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2(pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7)
- Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2(pre-dose,0.5,1,1.5,2,2.5,3,4,6 and 8 hours post dose on Day 1 and 6; pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7)