Healthy
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGPlacebo
Placebo
DRUGPF-07612577
PF-07612577
DRUGPF-06264006
PF-06264006
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participant and investigator-blinded and sponsor-open design for Part-1 and Part-2.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. BMI of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb) 2. For optional Japanese cohort only: Japanese participants who have 4 Japanese biologic grandparents who were born in Japan 3. For optional Chinese cohort only: Chinese participants who were born in mainland China, and both parents are of Chinese descent.
Exclusion criteria
1. 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) 2. Known allergy to the cephalosporin group of antibiotics 3. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed 4. 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 5. A positive urine drug test 6. Positive test result for SARS-CoV-2 infection at the time of screening or Day -1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 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). |
| Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1 | 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. |
| Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1 | 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 | 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 | 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 | 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. |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Aetau% was calculated as 100\*Aetau/Dose. |
| 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 | Aetau% was calculated as 100\*Aetau/Dose. |
| 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 | The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL. |
| 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 | The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL. |
| 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 | Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for TID dosing. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL. |
| 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 Cmax was determined as Cmax/Dose. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL. |
| 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 | Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for TID dosing. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL. |
| 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 | 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 cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL. |
| 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 | 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 cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL. |
| 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 | CL/F was calculated as Dose/AUCinf. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL. |
| 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 | — |
Countries
Belgium
Participant flow
Pre-assignment details
A total of 42 participants (8 in Part 1 and 34 in Part 2) were enrolled in the study. The study was conducted at 1 site in Belgium.
Participants by arm
| Arm | Count |
|---|---|
| CTB400+AVP900mg/CTB 800+AVP1350 mg /CTB800mg/ CTB1200+AVP1350 mg/Placebo for CTB 1600mg(Part1) Healthy participants were administered a single oral dose of ceftibuten(CTB) 400 milligrams (mg) along with Avibactam Prodrug (AVP) 900 mg on Day 1 of Period 1 followed by a single oral dose of CTB 800 mg along with AVP 1350 mg on Day 1 of Period 2. Participants received a single oral dose of CTB 800 mg alone on Day 1 of Period 3 followed by CTB 1200 mg with AVP 1350 mg and placebo for CTB 1600 mg orally on Day 1 of Period 4 and 5 respectively. There was a washout period of minimum 3 days between doses. | 2 |
| CTB400+AVP900mg /CTB800+AVP1350mg /CTB 800mg/Placebo for CTB1200+AVP1350 mg /CTB1600 mg(Part1) Healthy participants were administered a single oral dose of CTB 400 mg along with AVP 900 mg on Day 1 of Period 1 followed by a single oral dose of CTB 800 mg along with AVP 1350 mg on Day 1 of Period 2. Participants received a single oral dose of CTB 800 mg alone on Day 1 of Period 3 followed by a placebo of CTB 1200 mg along with AVP 1350 mg and CTB 1600 mg orally on Day 1 of Period 4 and 5 respectively. There was a washout period of minimum 3 days between doses. | 2 |
| CTB400+AVP900mg/ Placebo for CTB800+AVP1350mg/ Placebo CTB800mg/ CTB1200+AVP1350mg/ CTB1600mg(Part1) Healthy participants were administered a single oral dose of CTB 400 mg along with AVP 900 mg on Day 1 of Period 1 followed by a single oral dose of placebo for CTB 800 mg along with AVP 1350 mg on Day 1 of Period 2. Participants received a single oral dose of placebo for CTB 800 mg alone on Day 1 of Period 3 followed by CTB 1200 mg along with AVP 1350 mg and CTB 1600 mg orally on Day 1 of Period 4 and 5 respectively. There was a washout period of minimum 3 days between doses. | 2 |
| Placebo for CTB400+AVP900mg/ CTB 800+AVP1350mg/ CTB800mg/ CTB1200mg+AVP1350mg/ CTB1600mg(Part1) Healthy participants were administered a single oral dose of placebo for CTB 400 mg along with AVP 900 mg on Day 1 of Period 1 followed by a single oral dose of CTB 800 mg along with AVP 1350 mg on Day 1 of Period 2. Participants received a single oral dose of CTB 800 mg alone on Day 1 of Period 3 followed by CTB 1200 mg along with AVP 1350 mg and CTB 1600 mg orally on Day 1 of Period 4 and 5 respectively. There was a washout period of minimum 3 days between doses. | 2 |
| CTB 400 mg + AVP 1350 mg q8h (Part-2) Healthy participants were administered CTB 400 mg along with AVP 1350 mg once every 8 hours (q8h) in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 6 |
| Placebo for CTB 400 mg + AVP 1350 mg q8h (Part-2) Healthy participants were administered placebo for CTB 400 mg along with AVP 1350 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 2 |
| CTB 800 mg + AVP 1350 mg q8h (Part-2) Healthy participants were administered CTB 800 mg along with AVP 1350 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 6 |
| Placebo for CTB 800 mg + AVP 1350 mg q8h (Part-2) Healthy participants were administered placebo for CTB 800 mg along with AVP 1350 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 2 |
| CTB 400 mg + AVP 900 mg q8h (Part-2) Healthy participants were administered CTB 400 mg along with AVP 900 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 6 |
| Placebo for CTB 400 mg + AVP 900 mg q8h (Part-2) Healthy participants were administered placebo for CTB 400 mg along with AVP 900 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 2 |
| CTB 400 mg + AVP 1350 mg q8h (Japanese) (Part-2) Healthy Japanese participants were administered CTB 400 mg along with AVP 1350 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 5 |
| Placebo for CTB 400 mg + AVP 1350 mg q8h (Japanese) (Part-2) Healthy Japanese participants were administered placebo for CTB 400 mg along with AVP 1350 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 1 |
| CTB 400 mg + AVP 1350 mg q8h (Chinese) (Part-2) Healthy Chinese participants were administered CTB 400 mg along with AVP 1350 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 3 |
| Placebo for CTB 400 mg + AVP 1350 mg q8h (Chinese) (Part-2) Healthy Chinese participants were administered placebo for CTB 400 mg along with AVP 1350 mg q8h in a fed state on Days 1 to 6 and in a fasted state on Day 7. | 1 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 2 (7 Days) | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | CTB400+AVP900mg/CTB 800+AVP1350 mg /CTB800mg/ CTB1200+AVP1350 mg/Placebo for CTB 1600mg(Part1) | CTB400+AVP900mg /CTB800+AVP1350mg /CTB 800mg/Placebo for CTB1200+AVP1350 mg /CTB1600 mg(Part1) | CTB400+AVP900mg/ Placebo for CTB800+AVP1350mg/ Placebo CTB800mg/ CTB1200+AVP1350mg/ CTB1600mg(Part1) | Placebo for CTB400+AVP900mg/ CTB 800+AVP1350mg/ CTB800mg/ CTB1200mg+AVP1350mg/ CTB1600mg(Part1) | CTB 400 mg + AVP 1350 mg q8h (Part-2) | Placebo for CTB 400 mg + AVP 1350 mg q8h (Part-2) | CTB 800 mg + AVP 1350 mg q8h (Part-2) | Placebo for CTB 800 mg + AVP 1350 mg q8h (Part-2) | CTB 400 mg + AVP 900 mg q8h (Part-2) | Placebo for CTB 400 mg + AVP 900 mg q8h (Part-2) | CTB 400 mg + AVP 1350 mg q8h (Japanese) (Part-2) | Placebo for CTB 400 mg + AVP 1350 mg q8h (Japanese) (Part-2) | CTB 400 mg + AVP 1350 mg q8h (Chinese) (Part-2) | Placebo for CTB 400 mg + AVP 1350 mg q8h (Chinese) (Part-2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 Years | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 30 Participants |
| Age, Customized 45-64 Years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 10 Participants |
| Age, Customized Not disclosed | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 3 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not disclosed | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 6 Participants | 2 Participants | 4 Participants | 2 Participants | 6 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 30 Participants |
| Sex/Gender, Customized Female | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex/Gender, Customized Male | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants | 5 Participants | 0 Participants | 2 Participants | 0 Participants | 37 Participants |
| Sex/Gender, Customized Not disclosed | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 5 | 0 / 1 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 2 / 6 | 0 / 2 | 3 / 6 | 1 / 2 | 0 / 6 | 0 / 2 | 3 / 6 | 1 / 2 | 3 / 6 | 0 / 2 | 5 / 6 | 2 / 2 | 4 / 6 | 1 / 2 | 5 / 6 | 2 / 2 | 2 / 5 | 0 / 1 | 3 / 3 | 0 / 1 |
| serious Total, serious adverse events | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 5 | 0 / 1 | 0 / 3 | 0 / 1 |
Outcome results
Primary
Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1
CL/F was calculated as Dose/AUCinf.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter analysis set. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP). Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1 | HPA | 26.44 Liter per hour | Geometric Coefficient of Variation 24 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1 | AVI | 27.35 Liter per hour | Geometric Coefficient of Variation 34 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1 | AVI | 23.75 Liter per hour | Geometric Coefficient of Variation 13 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1 | HPA | 21.92 Liter per hour | Geometric Coefficient of Variation 10 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1 | AVI | 23.75 Liter per hour | Geometric Coefficient of Variation 19 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1 | HPA | 22.53 Liter per hour | Geometric Coefficient of Variation 22 |
| Unknown | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 1 | AVP | — Liter per hour | — |
Primary
Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2
CL/F was calculated as Dose/AUCinf.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 30.65 Liter per hour | Geometric Coefficient of Variation 16 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 32.89 Liter per hour | Geometric Coefficient of Variation 28 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 22.64 Liter per hour | Geometric Coefficient of Variation 32 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 19.28 Liter per hour | Geometric Coefficient of Variation 22 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 22.86 Liter per hour | Geometric Coefficient of Variation 14 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 23.41 Liter per hour | Geometric Coefficient of Variation 16 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 19.78 Liter per hour | Geometric Coefficient of Variation 22 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 23.61 Liter per hour | Geometric Coefficient of Variation 19 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 31.73 Liter per hour | Geometric Coefficient of Variation 23 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 32.38 Liter per hour | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 20.02 Liter per hour | Geometric Coefficient of Variation 21 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 20.25 Liter per hour | Geometric Coefficient of Variation 30 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 19.59 Liter per hour | Geometric Coefficient of Variation 16 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 19.02 Liter per hour | Geometric Coefficient of Variation 22 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 26.76 Liter per hour | Geometric Coefficient of Variation 15 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 20.13 Liter per hour | Geometric Coefficient of Variation 17 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 23.34 Liter per hour | Geometric Coefficient of Variation 9 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 28.07 Liter per hour | Geometric Coefficient of Variation 21 |
| Unknown | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVP Day 7 | — Liter per hour | — |
| Unknown | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVP Day 6 | — Liter per hour | — |
| Unknown | Apparent Clearance (CL/F) of AVP, AVI and HPA: Part 2 | AVP Day 1 | — Liter per hour | — |
Primary
Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2
CL/F was calculated as Dose/AUCinf.
Time frame: 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
Population: Pharmacokinetic parameter analysis set. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 4.61 Liter per hour | Geometric Coefficient of Variation 4.45 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 3.844 Liter per hour | Geometric Coefficient of Variation 10 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 3.914 Liter per hour | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 6 | 44.85 Liter per hour | Geometric Coefficient of Variation 12 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 7 | 39.67 Liter per hour | Geometric Coefficient of Variation 12 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 4.89 Liter per hour | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 4.774 Liter per hour | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 3.579 Liter per hour | Geometric Coefficient of Variation 23 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 4.283 Liter per hour | Geometric Coefficient of Variation 17 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 4.273 Liter per hour | Geometric Coefficient of Variation 8 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 5.014 Liter per hour | Geometric Coefficient of Variation 10 |
Primary
Apparent Clearance (CL/F) of CTB: Part 1
CL/F was calculated as Dose/AUCinf.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of CTB: Part 1 | 4.221 Liter per hour | Geometric Coefficient of Variation 18 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of CTB: Part 1 | 5.136 Liter per hour | Geometric Coefficient of Variation 13 |
| CTB 800 mg (Part-1) | Apparent Clearance (CL/F) of CTB: Part 1 | 4.620 Liter per hour | Geometric Coefficient of Variation 14 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of CTB: Part 1 | 6.492 Liter per hour | Geometric Coefficient of Variation 15 |
| CTB 1600 mg (Part-1) | Apparent Clearance (CL/F) of CTB: Part 1 | 4.973 Liter per hour | Geometric Coefficient of Variation 24 |
Primary
Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1
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.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter analysis set. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP). Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1 | HPA | 157.6 Liter | Geometric Coefficient of Variation 24 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1 | AVI | 154.6 Liter | Geometric Coefficient of Variation 27 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1 | AVI | 175.0 Liter | Geometric Coefficient of Variation 33 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1 | HPA | 163.2 Liter | Geometric Coefficient of Variation 35 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1 | AVI | 121.5 Liter | Geometric Coefficient of Variation 33 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1 | HPA | 122.7 Liter | Geometric Coefficient of Variation 36 |
| Unknown | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA : Part 1 | AVP | — Liter | — |
Primary
Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2
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.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVI Day 6 | NA Liter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 228.7 Liter | Geometric Coefficient of Variation 22 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | HPA Day 6 | NA Liter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 188.1 Liter | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 275.1 Liter | Geometric Coefficient of Variation 21 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | HPA Day 7 | NA Liter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 58.04 Liter | Geometric Coefficient of Variation 25 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 165.9 Liter | Geometric Coefficient of Variation 9 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 63.23 Liter | Geometric Coefficient of Variation 10 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 64.02 Liter | Geometric Coefficient of Variation 22 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 234.7 Liter | Geometric Coefficient of Variation 18 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | HPA Day 1 | NA Liter | — |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | HPA Day 6 | NA Liter | — |
| Unknown | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVP Day 7 | — Liter | — |
| Unknown | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVP Day 6 | — Liter | — |
| Unknown | Apparent Volume of Distribution (Vz/F) of AVP, AVI and HPA: Part 2 | AVP Day 1 | — Liter | — |
Primary
Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2
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.
Time frame: 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
Population: Pharmacokinetic parameter analysis set. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 1 | 16.5 Liter | Geometric Coefficient of Variation 13.7 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 6 | 16.5 Liter | Geometric Coefficient of Variation 13.8 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 7 | 20.86 Liter | Geometric Coefficient of Variation 22 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Trans-CTB Day 7 | 227.5 Liter | Geometric Coefficient of Variation 25 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 6 | 11.5 Liter | Geometric Coefficient of Variation 8.95 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 1 | 15.6 Liter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 7 | 26.76 Liter | Geometric Coefficient of Variation 36 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 6 | 14.8 Liter | Geometric Coefficient of Variation 11.2 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 7 | 18.58 Liter | Geometric Coefficient of Variation 13 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 1 | 15.37 Liter | Geometric Coefficient of Variation 15 |
Primary
Apparent Volume of Distribution (Vz/F) of CTB: Part 1
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.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of CTB: Part 1 | 18.44 Liter | Geometric Coefficient of Variation 20 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of CTB: Part 1 | 19.70 Liter | Geometric Coefficient of Variation 14 |
| CTB 800 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of CTB: Part 1 | 19.10 Liter | Geometric Coefficient of Variation 16 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of CTB: Part 1 | 29.28 Liter | Geometric Coefficient of Variation 14 |
| CTB 1600 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of CTB: Part 1 | 22.72 Liter | Geometric Coefficient of Variation 30 |
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1
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.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter analysis set. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP). Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1 | HPA | 10220 Nanogram*hours per milliliter | Geometric Coefficient of Variation 24 |
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1 | AVI | 22050 Nanogram*hours per milliliter | Geometric Coefficient of Variation 34 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1 | AVI | 38060 Nanogram*hours per milliliter | Geometric Coefficient of Variation 13 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1 | HPA | 18440 Nanogram*hours per milliliter | Geometric Coefficient of Variation 10 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1 | AVI | 38090 Nanogram*hours per milliliter | Geometric Coefficient of Variation 19 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1 | HPA | 17950 Nanogram*hours per milliliter | Geometric Coefficient of Variation 22 |
| Unknown | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of AVP, AVI and HPA: Part 1 | AVP | — Nanogram*hours per milliliter | — |
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1
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.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1 | 94730 Nanogram*hour per milliliter | Geometric Coefficient of Variation 18 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1 | 155800 Nanogram*hour per milliliter | Geometric Coefficient of Variation 13 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1 | 173200 Nanogram*hour per milliliter | Geometric Coefficient of Variation 14 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1 | 184900 Nanogram*hour per milliliter | Geometric Coefficient of Variation 15 |
| CTB 1600 mg (Part-1) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of CTB: Part 1 | 321900 Nanogram*hour per milliliter | Geometric Coefficient of Variation 24 |
90% CI: [87.47, 92.41]
Primary
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
AUClast was determined using the linear/log trapezoidal method. The lower limit of quantification for AVP was 1.0 ng/mL.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter analysis set. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP). Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | AVI | 21760 Nanogram*hours per milliliter | Geometric Coefficient of Variation 33 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | AVP | NA Nanogram*hours per milliliter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | HPA | 9996 Nanogram*hours per milliliter | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | AVI | 37000 Nanogram*hours per milliliter | Geometric Coefficient of Variation 13 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | AVP | NA Nanogram*hours per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | HPA | 17790 Nanogram*hours per milliliter | Geometric Coefficient of Variation 12 |
| CTB 800 mg (Part-1) | 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 | AVP | NA Nanogram*hours per milliliter | — |
| CTB 800 mg (Part-1) | 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 | HPA | 17670 Nanogram*hours per milliliter | Geometric Coefficient of Variation 23 |
| CTB 800 mg (Part-1) | 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 | AVI | 37680 Nanogram*hours per milliliter | Geometric Coefficient of Variation 19 |
Primary
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1
AUClast was determined using the linear/log trapezoidal method.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1 | 94050 Nanogram*hours per milliliter | Geometric Coefficient of Variation 18 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1 | 154100 Nanogram*hours per milliliter | Geometric Coefficient of Variation 14 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1 | 171800 Nanogram*hours per milliliter | Geometric Coefficient of Variation 15 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1 | 183600 Nanogram*hours per milliliter | Geometric Coefficient of Variation 15 |
| CTB 1600 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of CTB: Part 1 | 319200 Nanogram*hours per milliliter | Geometric Coefficient of Variation 24 |
90% CI: [87.24, 92.23]
Primary
Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2
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 frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 29480 Nanogram*hours per milliliter | Geometric Coefficient of Variation 16 |
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 17910 Nanogram*hours per milliliter | Geometric Coefficient of Variation 32 |
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 39570 Nanogram*hours per milliliter | Geometric Coefficient of Variation 14 |
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 21000 Nanogram*hours per milliliter | Geometric Coefficient of Variation 22 |
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 38670 Nanogram*hours per milliliter | Geometric Coefficient of Variation 16 |
| CTB 400 mg + AVP 900 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 12310 Nanogram*hours per milliliter | Geometric Coefficient of Variation 28 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 38300 Nanogram*hours per milliliter | Geometric Coefficient of Variation 19 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 12740 Nanogram*hours per milliliter | Geometric Coefficient of Variation 23 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 27920 Nanogram*hours per milliliter | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 45130 Nanogram*hours per milliliter | Geometric Coefficient of Variation 21 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 20020 Nanogram*hours per milliliter | Geometric Coefficient of Variation 30 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 20500 Nanogram*hours per milliliter | Geometric Coefficient of Variation 22 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 13790 Nanogram*hours per milliliter | Geometric Coefficient of Variation 16 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 22530 Nanogram*hours per milliliter | Geometric Coefficient of Variation 15 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 29920 Nanogram*hours per milliliter | Geometric Coefficient of Variation 17 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 25810 Nanogram*hours per milliliter | Geometric Coefficient of Variation 9 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 9623 Nanogram*hours per milliliter | Geometric Coefficient of Variation 22 |
| CTB 800 mg (Part-1) | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 14190 Nanogram*hours per milliliter | Geometric Coefficient of Variation 22 |
| Unknown | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVP Day 7 | — Nanogram*hours per milliliter | — |
| Unknown | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVP Day 6 | — Nanogram*hours per milliliter | — |
| Unknown | Area Under the Plasma Concentration Time Curve From Time Zero to Time Tau, the Dosing Interval (AUCtau) of AVP, AVI and HPA: Part 2 | AVP Day 1 | — Nanogram*hours per milliliter | — |
Comparison: AVI- Day 6 versus Day 790% CI: [90.37, 115.87]
Comparison: AVI- Day 6 versus Day 790% CI: [100.61, 138]
Comparison: AVI- Day 6 versus Day 790% CI: [104.12, 128.98]
Comparison: HPA- Day 6 versus Day 790% CI: [70.37, 103.32]
Comparison: HPA- Day 6 versus Day 790% CI: [78.83, 121.06]
Comparison: HPA- Day 6 versus Day 790% CI: [94.8, 111.58]
Primary
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
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 frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Trans-CTB Day 7 | 10060 Nanogram*hours per milliliter | Geometric Coefficient of Variation 12 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Cis-CTB Day 6 | 104200 Nanogram*hours per milliliter | Geometric Coefficient of Variation 10 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Cis-CTB Day 7 | 101900 Nanogram*hours per milliliter | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Trans-CTB Day 1 | 4112 Nanogram*hours per milliliter | Geometric Coefficient of Variation 13 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Trans-CTB Day 6 | 8968 Nanogram*hours per milliliter | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Cis-CTB Day 1 | 64640 Nanogram*hours per milliliter | Geometric Coefficient of Variation 14 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | Cis-CTB Day 1 | 113100 Nanogram*hours per milliliter | Geometric Coefficient of Variation 22 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | Cis-CTB Day 7 | 167600 Nanogram*hours per milliliter | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | Cis-CTB Day 6 | 224300 Nanogram*hours per milliliter | Geometric Coefficient of Variation 23 |
| CTB 800 mg (Part-1) | 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 | Cis-CTB Day 7 | 93660 Nanogram*hours per milliliter | Geometric Coefficient of Variation 8 |
| CTB 800 mg (Part-1) | 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 | Cis-CTB Day 1 | 67730 Nanogram*hours per milliliter | Geometric Coefficient of Variation 11 |
| CTB 800 mg (Part-1) | 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 | Cis-CTB Day 6 | 93590 Nanogram*hours per milliliter | Geometric Coefficient of Variation 17 |
Comparison: Cis-CTB Day 6 versus Day 790% CI: [88.67, 117.8]
Comparison: Cis-CTB Day 6 versus Day 790% CI: [119.84, 149.36]
Comparison: Cis-CTB Day 6 versus Day 790% CI: [90.7, 110.1]
Comparison: Trans-CTB Day 6 versus Day 790% CI: [75.27, 105.63]
Primary
Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1
AUCinf(dn) was calculated as AUCinf/Dose.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter analysis set. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP). Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1 | HPA | 37.86 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 24 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1 | AVI | 36.58 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 34 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1 | AVI | 42.10 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 13 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1 | HPA | 45.59 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 10 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1 | AVI | 42.11 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 19 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1 | HPA | 44.35 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 22 |
| Unknown | Dose-Normalized AUCinf (AUCinf[dn]) of AVP, AVI and HPA: Part 1 | AVP | — Nanogram*hour/milliliter/milligram | — |
Primary
Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1
AUCinf(dn) was calculated as AUCinf/Dose.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1 | 236.9 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 18 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1 | 194.6 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 13 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1 | 216.7 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 14 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1 | 153.8 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 15 |
| CTB 1600 mg (Part-1) | Dose-Normalized AUCinf (AUCinf[dn]) of CTB: Part 1 | 200.9 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 24 |
Primary
Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1
AUClast(dn) was determined as AUClast/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | AVI | 36.10 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 33 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | AVP | NA Nanogram*hour/milliliter/milligram | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | HPA | 37.04 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | AVI | 40.91 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 13 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | AVP | NA Nanogram*hour/milliliter/milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | HPA | 43.89 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 11 |
| CTB 800 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | AVP | NA Nanogram*hour/milliliter/milligram | — |
| CTB 800 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | HPA | 43.59 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 23 |
| CTB 800 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of AVP, AVI and HPA: Part 1 | AVI | 41.67 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 19 |
Primary
Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1
AUClast(dn) was determined as AUClast/Dose.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1 | 235.2 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 18 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1 | 192.9 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 14 |
| CTB 800 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1 | 214.9 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 15 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1 | 152.9 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 15 |
| CTB 1600 mg (Part-1) | Dose-Normalized AUClast (AUClast[dn]) of CTB: Part 1 | 199.6 Nanogram*hour/milliliter per milligram | Geometric Coefficient of Variation 24 |
Primary
Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2
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 frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 32.63 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 16 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 44.19 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 32 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 43.77 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 14 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 51.84 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 22 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 42.73 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 16 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 30.43 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 28 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 42.32 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 19 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 31.53 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 23 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 30.88 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 49.92 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 21 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 49.40 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 30 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 50.56 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 22 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 51.08 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 16 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 37.37 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 15 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 49.62 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 17 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 42.81 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 9 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 35.63 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 21 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 52.59 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 22 |
| Unknown | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 7 | — Nanogram*hour/milliliter/milligram | — |
| Unknown | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 6 | — Nanogram*hour/milliliter/milligram | — |
| Unknown | Dose-Normalized AUCtau (AUCtau[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 1 | — Nanogram*hour/milliliter/milligram | — |
Primary
Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2
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 frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 7 | 25.20 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 12 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 260.4 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 9 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 255.6 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 1 | 10.28 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 13 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 6 | 22.45 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 161.6 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 14 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 141.6 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 22 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 209.8 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 280.7 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 23 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 234.1 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 8 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 169.5 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 11 |
| CTB 800 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 234.2 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 17 |
Primary
Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | AVI | 6.388 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 44 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | AVP | NA Nanogram per milliliter per milligram | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | HPA | 5.635 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 33 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | AVI | 6.583 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 13 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | AVP | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | HPA | 6.300 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 14 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | AVP | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | HPA | 6.608 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 36 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 1 | AVI | 7.422 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 26 |
Primary
Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for AVP was 1.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 6.907 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 25 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 9.824 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 23 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 9.373 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 12 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 8.786 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 15 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 1 | NA Nanogram per milliliter per milligram | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 7.939 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 28 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 7 | NA Nanogram per milliliter per milligram | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 6 | NA Nanogram per milliliter per milligram | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 6.340 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 29 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 9.587 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 37 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 1 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 6 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 7 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 6.470 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 12 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 8.483 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 20 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 6.270 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 10 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 8.471 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 35 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 9.430 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 21 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 7 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 1 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 7.324 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 25 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVP Day 6 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 10.02 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 15 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 10.21 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 15 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 7.927 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 27 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 9.782 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 20 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 9.544 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 12 |
Primary
Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2
Dose-normalized Cmax was determined as Cmax/Dose.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Trans-CTB Day 7 | 4.105 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 15 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 6 | 56.59 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 7 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 7 | 54.21 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 17 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Trans-CTB Day 1 | 2.089 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 17 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Trans-CTB Day 6 | 3.572 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 12 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 1 | 36.56 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 21 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 1 | 28.43 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 26 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 7 | 44.08 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 25 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 6 | 57.06 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 24 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 7 | 51.00 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 10 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 1 | 43.22 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 11 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB and Trans-CTB : Part 2 | Cis-CTB Day 6 | 51.72 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 16 |
Primary
Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1
Dose-normalized Cmax was determined as Cmax/Dose.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1 | 45.45 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1 | 31.83 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 18 |
| CTB 800 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1 | 38.16 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 16 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1 | 22.61 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 12 |
| CTB 1600 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of CTB: Part 1 | 28.12 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 25 |
Primary
Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2
The lower limit of quantification for AVP was 1.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 7940 Nanogram per milliliter | Geometric Coefficient of Variation 15 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 3216 Nanogram per milliliter | Geometric Coefficient of Variation 28 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 8474 Nanogram per milliliter | Geometric Coefficient of Variation 12 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 6 | NA Nanogram per milliliter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 2568 Nanogram per milliliter | Geometric Coefficient of Variation 29 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 1 | NA Nanogram per milliliter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 6249 Nanogram per milliliter | Geometric Coefficient of Variation 25 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 7 | NA Nanogram per milliliter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 3986 Nanogram per milliliter | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 8676 Nanogram per milliliter | Geometric Coefficient of Variation 37 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 6 | NA Nanogram per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 7 | NA Nanogram per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 5852 Nanogram per milliliter | Geometric Coefficient of Variation 12 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 7673 Nanogram per milliliter | Geometric Coefficient of Variation 20 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 2539 Nanogram per milliliter | Geometric Coefficient of Variation 10 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 3432 Nanogram per milliliter | Geometric Coefficient of Variation 35 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 3817 Nanogram per milliliter | Geometric Coefficient of Variation 21 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 1 | NA Nanogram per milliliter | — |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 6 | NA Nanogram per milliliter | — |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 2643 Nanogram per milliliter | Geometric Coefficient of Variation 20 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 4779 Nanogram per milliliter | Geometric Coefficient of Variation 27 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 1 | NA Nanogram per milliliter | — |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 2707 Nanogram per milliliter | Geometric Coefficient of Variation 15 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 5753 Nanogram per milliliter | Geometric Coefficient of Variation 12 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVP Day 7 | NA Nanogram per milliliter | — |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 1977 Nanogram per milliliter | Geometric Coefficient of Variation 25 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 6159 Nanogram per milliliter | Geometric Coefficient of Variation 15 |
Comparison: AVI- Day 6 versus Day 790% CI: [78.37, 112.02]
Comparison: AVI-CTB Day 6 versus Day 790% CI: [88.31, 144.76]
Comparison: AVI- Day 6 versus Day 790% CI: [92.77, 123.54]
Comparison: HPA- Day 6 versus Day 790% CI: [68.32, 95.27]
Comparison: HPA- Day 6 versus Day 790% CI: [69.7, 116.02]
Comparison: HPA- Day 6 versus Day 790% CI: [84.08, 113.41]
Primary
Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1
The lower limit of quantification for AVP was 1.0 ng/mL.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | AVI | 3856 Nanogram per milliliter | Geometric Coefficient of Variation 44 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | AVP | NA Nanogram per milliliter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | HPA | 1521 Nanogram per milliliter | Geometric Coefficient of Variation 33 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | AVI | 5955 Nanogram per milliliter | Geometric Coefficient of Variation 13 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | AVP | NA Nanogram per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | HPA | 2552 Nanogram per milliliter | Geometric Coefficient of Variation 14 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | AVP | NA Nanogram per milliliter | — |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | HPA | 2676 Nanogram per milliliter | Geometric Coefficient of Variation 36 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of AVP, Avibactam (AVI) and Hydroxy Pivalic Acid (HPA): Part 1 | AVI | 6714 Nanogram per milliliter | Geometric Coefficient of Variation 26 |
Primary
Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1 | 18170 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1 | 25470 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1 | 30510 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 16 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1 | 27120 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12 |
| CTB 1600 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-Ceftibuten (CTB): Part 1 | 44990 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
90% CI: [74.67, 93.29]
Primary
Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 7 | 1641 Nanogram per milliliter | Geometric Coefficient of Variation 15 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 22630 Nanogram per milliliter | Geometric Coefficient of Variation 7 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 21660 Nanogram per milliliter | Geometric Coefficient of Variation 17 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 1 | 834.7 Nanogram per milliliter | Geometric Coefficient of Variation 17 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 6 | 1428 Nanogram per milliliter | Geometric Coefficient of Variation 12 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 14610 Nanogram per milliliter | Geometric Coefficient of Variation 21 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 22730 Nanogram per milliliter | Geometric Coefficient of Variation 26 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 35240 Nanogram per milliliter | Geometric Coefficient of Variation 25 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 45640 Nanogram per milliliter | Geometric Coefficient of Variation 24 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 20390 Nanogram per milliliter | Geometric Coefficient of Variation 10 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 17270 Nanogram per milliliter | Geometric Coefficient of Variation 11 |
| CTB 800 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 20680 Nanogram per milliliter | Geometric Coefficient of Variation 16 |
Comparison: Cis-CTB Day 6 versus Day 790% CI: [84.94, 128.5]
Comparison: Cis-CTB Day 6 versus Day 790% CI: [119.37, 140.58]
Comparison: Cis-CTB Day 6 versus Day 790% CI: [88.68, 116.08]
Comparison: Trans-CTB Day 6 versus Day 790% CI: [74.48, 101.59]
Primary
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1
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.
Time frame: Up to 24 hours post-dose
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 1 | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2
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.
Time frame: From start of treatment up to Day 7
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: Part 2 | 0 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1
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).
Time frame: Up to 24 hours post-dose
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 1 | 0 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2
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).
Time frame: From start of treatment up to Day 7
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Electrocardiogram (ECG) Abnormalities: Part 2 | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities: Part 1
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).
Time frame: Up to 24 hours post-dose
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 0 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 1 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 1 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 1 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 1 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 1 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 3 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Urine Hemoglobin (Scalar) | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Monocytes/Leukocytes | 1 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 1 | Leukocyte Esterase (Scalar) | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities: Part 2
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).
Time frame: From start of treatment up to Day 7
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 1 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 0 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 1 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 1 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 1 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 2 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 1 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 1 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 1 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 1 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 4 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 1 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 1 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Bicarbonate | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine glucose | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Urine hemoglobin (scalar) | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Leukocyte esterase (scalar) | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Ketones (scalar) | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Monocytes/leukocytes | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Eosinophils/leukocytes | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Laboratory Test Abnormalities: Part 2 | Neutrophils/leukocytes | 0 Participants |
Primary
Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2
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.
Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 5 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 4 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 1 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 2 Participants |
| CTB 800 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 4 Participants |
| CTB 800 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 4 Participants |
| CTB 800 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 5 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 3 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 2 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 2 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 2 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 3 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 3 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | TEAEs | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Related TEAEs | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With TEAEs, Severe TEAEs and Related TEAEs: Part 2 | Severe TEAEs | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1
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.
Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 2 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 1 Participants |
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 3 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 3 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 2 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 1 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 3 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 3 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | TEAEs | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Related TEAEs | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs and Related TEAEs: Part 1 | Severe TEAEs | 0 Participants |
Primary
Number of Participants With Withdrawals Due to TEAEs: Part 1
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.
Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 52 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 1 | 0 Participants |
Primary
Number of Participants With Withdrawals Due to TEAEs: Part 2
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.
Time frame: From start of treatment up to 28 to 35 days post last dose of study intervention (approximately 42 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and received at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 2 Participants |
| CTB 800 mg + AVP 1350 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 0 Participants |
| CTB 800 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 0 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 0 Participants |
| Placebo for CTB 800 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 1 Participants |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 0 Participants |
| Placebo for CTB 1200 mg + AVP 1350 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 0 Participants |
| CTB 1600 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 1 Participants |
| Placebo for CTB 1600 mg (Part-1) | Number of Participants With Withdrawals Due to TEAEs: Part 2 | 0 Participants |
Primary
Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2
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.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on day 7
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2 | HPA Day 7 | 6.270 hours | Standard Deviation 0.64211 |
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2 | AVI Day 7 | 6.473 hours | Standard Deviation 1.0929 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2 | AVI Day 7 | 8.165 hours | Standard Deviation 1.3241 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2 | HPA Day 7 | NA hours | — |
| CTB 800 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2 | AVI Day 7 | 7.150 hours | Standard Deviation 1.8379 |
| CTB 800 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2 | HPA Day 7 | 5.965 hours | Standard Deviation 1.1229 |
| Unknown | Terminal Half-Life (t1/2) of AVP, AVI and HPA on Day 7: Part 2 | AVP Day 7 | — hours | — |
Primary
Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1
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.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter analysis set. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP). Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1 | HPA | 4.218 Hours | Standard Deviation 0.9209 |
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1 | AVI | 4.043 Hours | Standard Deviation 1.0748 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1 | AVI | 5.302 Hours | Standard Deviation 1.4722 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1 | HPA | 5.347 Hours | Standard Deviation 1.5405 |
| CTB 800 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1 | AVI | 3.632 Hours | Standard Deviation 0.86092 |
| CTB 800 mg (Part-1) | Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1 | HPA | 3.853 Hours | Standard Deviation 0.8671 |
| Unknown | Terminal Half-Life (t1/2) of AVP, AVI and HPA: Part 1 | AVP | — Hours | — |
Primary
Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2
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.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,16 and 24 hours post dose on Day 7
Population: Pharmacokinetic parameter analysis set. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2 | Cis-CTB Day 7 | 3.710 hours | Standard Deviation 0.47011 |
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2 | Trans-CTB Day 7 | 4.040 hours | Standard Deviation 0.84699 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2 | Cis-CTB Day 7 | 3.930 hours | Standard Deviation 0.61106 |
| CTB 800 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB and Trans-CTB on Day 7: Part 2 | Cis-CTB Day 7 | 3.030 hours | Standard Deviation 0.32668 |
Primary
Terminal Half-Life (t1/2) of CTB: Part 1
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.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of CTB: Part 1 | 3.073 Hours | Standard Deviation 0.54265 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of CTB: Part 1 | 2.708 Hours | Standard Deviation 0.57031 |
| CTB 800 mg (Part-1) | Terminal Half-Life (t1/2) of CTB: Part 1 | 2.908 Hours | Standard Deviation 0.53905 |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of CTB: Part 1 | 3.138 Hours | Standard Deviation 0.276 |
| CTB 1600 mg (Part-1) | Terminal Half-Life (t1/2) of CTB: Part 1 | 3.180 Hours | Standard Deviation 0.28817 |
Primary
Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1
The lower limit of quantification for AVP was 1.0 ng/mL.
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter analysis set. Data is reported for CTB 400 mg + AVP 900 mg, CTB 800 mg + AVP 1350 mg and CTB 1200 mg + AVP 1350 mg arms only as only participants from these arms received AVP (AVI and HPA: metabolites of AVP). Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1 | HPA | 4.01 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1 | AVP | NA Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1 | AVI | 4.01 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1 | HPA | 4.00 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1 | AVI | 3.50 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1 | HPA | 4.50 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1 | AVP | NA Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 1 | AVI | 4.50 Hours |
Primary
Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2
The lower limit of quantification for AVP was 1.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 4.02 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 2.52 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 1.75 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 2.77 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 1.75 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 5.02 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 2.50 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 4.00 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 4.00 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 2.00 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 2.50 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 2.26 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 7 | 2.30 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 6 | 2.75 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVP Day 7 | NA Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 1 | 4.49 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVI Day 7 | 2.54 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 1 | 4.49 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | HPA Day 6 | 2.02 Hours |
| Unknown | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVP Day 6 | — Hours |
| Unknown | Time for Cmax (Tmax) of AVP, AVI and HPA: Part 2 | AVP Day 1 | — Hours |
Primary
Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Trans-CTB was measured only for CTB400 mg+AVP 1350 mg q8h arm as pre-specified in the protocol. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 7 | 3.54 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 2.54 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 2.05 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 1 | 5.13 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Trans-CTB Day 6 | 3.54 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 2.80 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 3.53 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 2.03 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 3.53 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 7 | 2.29 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 1 | 2.53 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB and Trans-CTB: Part 2 | Cis-CTB Day 6 | 3.28 Hours |
Primary
Time for Cmax (Tmax) of CTB: Part 1
Time frame: pre-dose,0.5,1,1.5,2,2.5,3,4,6,8,12,14 and 24 hours post dose
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of CTB: Part 1 | 3.21 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of CTB: Part 1 | 4.03 Hours |
| CTB 800 mg (Part-1) | Time for Cmax (Tmax) of CTB: Part 1 | 3.50 Hours |
| CTB 1200 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of CTB: Part 1 | 5.05 Hours |
| CTB 1600 mg (Part-1) | Time for Cmax (Tmax) of CTB: Part 1 | 4.01 Hours |
Secondary
Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2
Time frame: anytime between 0 to 8 hours post dose on Day 6
Population: Pharmacokinetic analysis set. Data was planned to be analyzed for CTB 400 mg + AVP 1350 mg arm only as pre-specified in the protocol. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2 | Cis CTB Day 6 | 181.8 Milligrams | Geometric Coefficient of Variation 98 |
| CTB 400 mg + AVP 900 mg (Part-1) | Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2 | Trans CTB Day 6 | 48.23 Milligrams | Geometric Coefficient of Variation 54 |
| CTB 400 mg + AVP 900 mg (Part-1) | Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2 | AVI Day 6 | 295.6 Milligrams | Geometric Coefficient of Variation 101 |
| CTB 400 mg + AVP 900 mg (Part-1) | Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of Cis-CTB, Trans-CTB, AVP, AVI and HPA: Part 2 | HPA Day 6 | 22.01 Milligrams | Geometric Coefficient of Variation 51 |
Secondary
Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
CL/F was calculated as Dose/AUCinf. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | 27.33 Liter/hour | Geometric Coefficient of Variation 8 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 40.66 Liter/hour | Geometric Coefficient of Variation 33 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 38.94 Liter/hour | Geometric Coefficient of Variation 35 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | 4.428 Liter/hour | Geometric Coefficient of Variation 9 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | 21.12 Liter/hour | Geometric Coefficient of Variation 7 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | 23.80 Liter/hour | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | 21.42 Liter/hour | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | 4.303 Liter/hour | Geometric Coefficient of Variation 9 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | NA Liter/hour | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | NA Liter/hour | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | NA Liter/hour | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | NA Liter/hour | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 27.69 Liter/hour | Geometric Coefficient of Variation 32 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | NA Liter/hour | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | NA Liter/hour | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 24.26 Liter/hour | Geometric Coefficient of Variation 35 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Clearance (CL/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | NA Liter/hour | — |
Secondary
Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
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 cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | 207.9 Liter | Geometric Coefficient of Variation 43 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | 12.82 Liter | Geometric Coefficient of Variation 8 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | NA Liter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | NA Liter | — |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | 156.0 Liter | Geometric Coefficient of Variation 44 |
| CTB 400 mg + AVP 900 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | 17.33 Liter | Geometric Coefficient of Variation 31 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | NA Liter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | NA Liter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | NA Liter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | NA Liter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | NA Liter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Apparent Volume of Distribution (Vz/F) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | NA Liter | — |
Secondary
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
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for TID dosing. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Cis CTB Day 6 | 92920 Nanogram*hours per milliliter | Geometric Coefficient of Variation 9 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | AVI Day 7 | 33100 Nanogram*hours per milliliter | Geometric Coefficient of Variation 8 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | AVI Day 1 | 22240 Nanogram*hours per milliliter | Geometric Coefficient of Variation 33 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | HPA Day 1 | 10400 Nanogram*hours per milliliter | Geometric Coefficient of Variation 35 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Cis CTB Day 7 | 90270 Nanogram*hours per milliliter | Geometric Coefficient of Variation 9 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | HPA Day 6 | 19160 Nanogram*hours per milliliter | Geometric Coefficient of Variation 7 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | AVI Day 6 | 38010 Nanogram*hours per milliliter | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | HPA Day 7 | 18890 Nanogram*hours per milliliter | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Cis CTB Day 1 | 52630 Nanogram*hours per milliliter | Geometric Coefficient of Variation 20 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | HPA Day 7 | NA Nanogram*hours per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | Cis CTB Day 1 | 84790 Nanogram*hours per milliliter | Geometric Coefficient of Variation 17 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | Cis CTB Day 6 | NA Nanogram*hours per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | Cis CTB Day 7 | NA Nanogram*hours per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | AVI Day 1 | 32650 Nanogram*hours per milliliter | Geometric Coefficient of Variation 32 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | AVI Day 6 | NA Nanogram*hours per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | AVI Day 7 | NA Nanogram*hours per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | HPA Day 1 | 16670 Nanogram*hours per milliliter | Geometric Coefficient of Variation 35 |
| CTB 800 mg + AVP 1350 mg (Part-1) | 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 | HPA Day 6 | NA Nanogram*hours per milliliter | — |
Comparison: AVI- Day 6 versus Day 790% CI: [101.1, 130.43]
Comparison: AVI- Day 6 versus Day 790% CI: [104.17, 189.34]
Comparison: HPA- Day 6 versus Day 790% CI: [90.79, 113.39]
Comparison: HPA- Day 6 versus Day 790% CI: [110.25, 137.67]
Secondary
Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Area under the plasma concentration time profile from time zero to time tau, the dosing interval, where tau is equal to 8 hours for TID dosing. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | 232.3 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 9 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | 36.59 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 8 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 24.62 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 33 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 25.70 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 35 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | 225.9 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 9 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | 47.29 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 7 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | 42.01 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | 46.65 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | 131.5 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 19 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | NA Nanogram*hour/milliliter/milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | 212.0 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 17 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | NA Nanogram*hour/milliliter/milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | NA Nanogram*hour/milliliter/milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 36.10 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 32 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | NA Nanogram*hour/milliliter/milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | NA Nanogram*hour/milliliter/milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 41.23 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 35 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized AUCtau (AUCtau[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | NA Nanogram*hour/milliliter/milligram | — |
Secondary
Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
Dose-normalized Cmax was determined as Cmax/Dose. The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | 55.21 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | 8.046 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 15 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 5.714 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 49 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 5.549 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 45 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | 53.35 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 14 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | 8.339 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 14 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | 8.483 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 24 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | 9.145 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 8 |
| CTB 400 mg + AVP 900 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | 34.16 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 35 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | 48.90 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 16 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 7.582 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | NA Nanogram per milliliter per milligram | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 8.249 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 33 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Dose-Normalized Cmax (Cmax[dn]) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | NA Nanogram per milliliter per milligram | — |
Secondary
Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | 22080 Nanogram per milliliter | Geometric Coefficient of Variation 11 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | 7279 Nanogram per milliliter | Geometric Coefficient of Variation 15 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 5167 Nanogram per milliliter | Geometric Coefficient of Variation 49 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 2248 Nanogram per milliliter | Geometric Coefficient of Variation 45 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | 21330 Nanogram per milliliter | Geometric Coefficient of Variation 14 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | 3380 Nanogram per milliliter | Geometric Coefficient of Variation 14 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | 7677 Nanogram per milliliter | Geometric Coefficient of Variation 24 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | 3708 Nanogram per milliliter | Geometric Coefficient of Variation 8 |
| CTB 400 mg + AVP 900 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | 13660 Nanogram per milliliter | Geometric Coefficient of Variation 35 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | NA Nanogram per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | 19540 Nanogram per milliliter | Geometric Coefficient of Variation 16 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | NA Nanogram per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | NA Nanogram per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 6858 Nanogram per milliliter | Geometric Coefficient of Variation 24 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | NA Nanogram per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | NA Nanogram per milliliter | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 3341 Nanogram per milliliter | Geometric Coefficient of Variation 33 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Maximum Observed Concentration (Cmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | NA Nanogram per milliliter | — |
Comparison: AVI- Day 6 versus Day 790% CI: [86.64, 128.39]
Comparison: AVI- Day 6 versus Day 790% CI: [51.81, 347.81]
Comparison: HPA- Day 6 versus Day 790% CI: [79.54, 104.51]
Comparison: HPA- Day 6 versus Day 790% CI: [71.46, 185.9]
Secondary
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
Aetau% was calculated as 100\*Aetau/Dose.
Time frame: anytime between 0 to 8 hours post dose on Day 6
Population: Pharmacokinetic analysis set. Data was planned to be analyzed for CTB 400 mg + AVP 1350 mg arm only as pre-specified in the protocol. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Cis CTB Day 6 | 45.40 Percentage of dose excreted | Geometric Coefficient of Variation 98 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | Trans CTB Day 6 | 12.08 Percentage of dose excreted | Geometric Coefficient of Variation 55 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | AVI Day 6 | 32.68 Percentage of dose excreted | Geometric Coefficient of Variation 101 |
| CTB 400 mg + AVP 900 mg (Part-1) | 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 | HPA Day 6 | 5.434 Percentage of dose excreted | Geometric Coefficient of Variation 51 |
Secondary
Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2
Aetau% was calculated as 100\*Aetau/Dose.
Time frame: anytime between 0 to 8 hours post dose on Day 6
Population: Pharmacokinetic analysis set. Data was planned to be analyzed for CTB 400 mg + AVP 1350 mg arm only as pre-specified in the protocol. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2 | Cis CTB Day 6 | 2.501 Liter per hour | Geometric Coefficient of Variation 27 |
| CTB 400 mg + AVP 900 mg (Part-1) | Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2 | Trans CTB Day 6 | 6.657 Liter per hour | Geometric Coefficient of Variation 27 |
| CTB 400 mg + AVP 900 mg (Part-1) | Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2 | AVI Day 6 | 10.61 Liter per hour | Geometric Coefficient of Variation 34 |
| CTB 400 mg + AVP 900 mg (Part-1) | Renal Clearance (CLr) of Cis-CTB, Trans-CTBa, AVP, AVI and HPA: Part 2 | HPA Day 6 | 1.390 Liter per hour | Geometric Coefficient of Variation 22 |
Secondary
Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
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 cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic analysis set. It was planned to report data for CTB 400 mg + AVP 1350 mg only. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | 2.788 Hours | Standard Deviation 0.8067 |
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | 5.734 Hours | Standard Deviation 2.6304 |
| CTB 400 mg + AVP 900 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | 5.290 Hours | Standard Deviation 1.7122 |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | NA Hours | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | NA Hours | — |
| CTB 800 mg + AVP 1350 mg (Part-1) | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | NA Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | — Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | — Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | — Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | — Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | — Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVP Day 1 | — Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVP Day 6 | — Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVP Day 7 | — Hours | — |
| Unknown | Terminal Half-Life (t1/2) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | — Hours | — |
Secondary
Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2
The lower limit of quantification for cis-CTB was 100.0 ng/mL, and for AVI and HPA was 10.0 ng/mL.
Time frame: 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
Population: Pharmacokinetic parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported for the given part of the study. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | 3.03 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | 1.50 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 6.00 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 6.00 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | 2.03 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | 2.50 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | 4.00 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | 2.00 Hours |
| CTB 400 mg + AVP 900 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | 4.03 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 7 | NA Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 1 | 3.05 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 6 | NA Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | Cis CTB Day 7 | NA Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 1 | 3.02 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 6 | NA Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | AVI Day 7 | NA Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 1 | 4.00 Hours |
| CTB 800 mg + AVP 1350 mg (Part-1) | Time for Cmax (Tmax) of Cis-CTB, AVP, AVI and HPA in Japanese and Chinese Cohorts: Part 2 | HPA Day 6 | NA Hours |