Trial Outcomes & Findings for Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and to Evaluate the Interaction Between GSK3915393 and Grapefruit Juice and Itraconazole (NCT NCT04604795)
NCT ID: NCT04604795
Last Updated: 2023-05-09
Results Overview
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
65 participants
Primary outcome timeframe
Up to 70 days
Results posted on
2023-05-09
Participant Flow
This was a 3-part study in healthy participants. Part A was a crossover design, single-dose (SD), Part B was a parallel group, repeat oral dose and Part C was a drug:drug interaction study.
Total 65 participants were enrolled at one center in United Kingdom. The dose escalation committee concluded that doses higher than 160 milligram (mg) once daily (QD) (Part A Period 4 dose) should not be given. Placebo arms across similar dosing strategies in Part B were combined as pre-specified in reporting and analysis plan.
Participant milestones
| Measure |
PartA: Placebo/GSK3915393 60mg/100mcg IV/160mg
Participants in Part A received a single oral dose of Placebo on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 milligrams (mg) on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 micrograms (mcg) intravenous (IV) on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4. Participants were dosed in the fed state. There was a washout period of 20 days between periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
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Part A: GSK3915393 15mg/Placebo/100mcg IV/160mg
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160mg on Day 1 in treatment Period 4. Participants were dose in the fed state. There was a washout period of 20 days between periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
|
Part A: GSK3915393 15mg/60mg/100mcg IV/Placebo
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of placebo on Day 1 in treatment Period 4. Participants were dosed in fed state. There was a washout period of 20 days between Periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
|
Part A: GSK3915393 15mg/60mg/100mcg IV/160mg
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4. Participants were dosed in fed state. There was a washout period of 20 days between Period 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment period 3 and 4 was of 20 days. There was follow-up period of 14 days.
|
Part B: Placebo
Participants received placebo matching with GSK3915393 as repeat oral dose for 14 days (dosing frequency twice a day \[BID\] or QD, matched to the frequency of dosing in the concurrent active treatment arm). The impact of food effect on pharmacokinetic (PK) of GSK3915393 was investigated following Ante-Meridiem (AM) dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 20 mg (BID)
Participants received GSK3915393 20 mg BID as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 80 mg (BID)
Participants received GSK3915393 80 mg BID as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 160 mg (QD)
Participants received GSK3915393 160 mg QD as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
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PartC:GSK3915393 100mcg IV/100mcgIV+ITZ/20mg+GFJ/20+WTR/20+ITZ
Participants in Part C received a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 1; followed by a single dose of GSK3915393 100mcg IV along with Itraconazole (ITZ) on Day 1 in treatment Period 2; followed by a single oral dose of GSK3915393 20 mg along with grapefruit juice (GFJ) on Day 1 in treatment Period 3; followed by a single oral dose of GSK3915393 20mg along with water (WTR) on Day 1 in treatment Period 4; further followed by a single oral dose of GSK3915393 20 mg along with ITZ in treatment Period 5. There was a washout period of 6 days between treatment Periods 1 and 2, washout period of 24 days between treatment periods 2 and 3, washout period of 10 days between treatment periods 3 and 4 and washout period of 13 days between treatment periods 4 and 5. There was a follow-up of 14 days.
|
Part C:GSK3915393 100mg IV/100mcgIV+ITZ/20mg+WTR/20+GFJ/20+ITZ
Participants in Part C received a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 1; followed by a single dose of GSK3915393 100 mcg IV along with ITZ on Day 1 in treatment Period 2; followed by a single oral dose of GSK3915393 20 mg+ water on Day 1 in treatment Period 3; followed by a single oral dose of GSK3915393 20mg along with GFJ on Day 1 in treatment Period 4; further followed by a single oral dose of GSK3915393 20 mg along with ITZ in treatment Period 5. There was a washout period of 6 days between treatment Periods 1 and 2, washout period of 24 days between treatment periods 2 and 3, washout period of 10 days between treatment periods 3 and 4 and washout period of 13 days between treatment periods 4 and 5. There was a follow-up of 14 days.
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Part A: Period 1 (Day 1)
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Part A: Washout Period 1(Up to Day 20)
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Part A: Washout Period 1(Up to Day 20)
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Part A: Period 2 (Day 1)
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Part A: Washout Period 2 (Up to Day 12)
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Part A: Period 3 (Day 1)
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Part A: Period 3 (Day 1)
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Part A: Washout Period 3 (Up to Day 20)
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Part A: Washout Period 3 (Up to Day 20)
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Part A: Period 4 (Day 1)
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Part A: Period 4 (Day 1)
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Part B: Up to Day 14
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Part B: Up to Day 14
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Part B: Up to Day 14
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Part C: Period 1 (Day 1)
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Part C: Period 1 (Day 1)
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Part C: Washout Period 1 (Up to Day 6)
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Part C: Washout Period 1 (Up to Day 6)
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Part C: Period 2 (Day 1)
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Part C: Washout Period 2 (Up to Day 24)
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Part C: Washout Period 2 (Up to Day 24)
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Part C: Period 3 (Day 1)
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Part C: Period 3 (Day 1)
New Participant Enrolled and Dosed
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Part C: Period 3 (Day 1)
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Part C: Washout Period 3 (Up to Day10)
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Part C: Washout Period 3 (Up to Day10)
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Part C: Period 4 (Day 1)
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Part C: Period 4 (Day 1)
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Part C: Washout Period 4 (Up to Day 13)
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Part C: Washout Period 4 (Up to Day 13)
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Part C: Period 5 (Day 1)
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Part C: Period 5 (Day 1)
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Reasons for withdrawal
| Measure |
PartA: Placebo/GSK3915393 60mg/100mcg IV/160mg
Participants in Part A received a single oral dose of Placebo on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 milligrams (mg) on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 micrograms (mcg) intravenous (IV) on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4. Participants were dosed in the fed state. There was a washout period of 20 days between periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
|
Part A: GSK3915393 15mg/Placebo/100mcg IV/160mg
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160mg on Day 1 in treatment Period 4. Participants were dose in the fed state. There was a washout period of 20 days between periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
|
Part A: GSK3915393 15mg/60mg/100mcg IV/Placebo
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of placebo on Day 1 in treatment Period 4. Participants were dosed in fed state. There was a washout period of 20 days between Periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
|
Part A: GSK3915393 15mg/60mg/100mcg IV/160mg
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4. Participants were dosed in fed state. There was a washout period of 20 days between Period 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment period 3 and 4 was of 20 days. There was follow-up period of 14 days.
|
Part B: Placebo
Participants received placebo matching with GSK3915393 as repeat oral dose for 14 days (dosing frequency twice a day \[BID\] or QD, matched to the frequency of dosing in the concurrent active treatment arm). The impact of food effect on pharmacokinetic (PK) of GSK3915393 was investigated following Ante-Meridiem (AM) dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 20 mg (BID)
Participants received GSK3915393 20 mg BID as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 80 mg (BID)
Participants received GSK3915393 80 mg BID as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 160 mg (QD)
Participants received GSK3915393 160 mg QD as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
PartC:GSK3915393 100mcg IV/100mcgIV+ITZ/20mg+GFJ/20+WTR/20+ITZ
Participants in Part C received a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 1; followed by a single dose of GSK3915393 100mcg IV along with Itraconazole (ITZ) on Day 1 in treatment Period 2; followed by a single oral dose of GSK3915393 20 mg along with grapefruit juice (GFJ) on Day 1 in treatment Period 3; followed by a single oral dose of GSK3915393 20mg along with water (WTR) on Day 1 in treatment Period 4; further followed by a single oral dose of GSK3915393 20 mg along with ITZ in treatment Period 5. There was a washout period of 6 days between treatment Periods 1 and 2, washout period of 24 days between treatment periods 2 and 3, washout period of 10 days between treatment periods 3 and 4 and washout period of 13 days between treatment periods 4 and 5. There was a follow-up of 14 days.
|
Part C:GSK3915393 100mg IV/100mcgIV+ITZ/20mg+WTR/20+GFJ/20+ITZ
Participants in Part C received a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 1; followed by a single dose of GSK3915393 100 mcg IV along with ITZ on Day 1 in treatment Period 2; followed by a single oral dose of GSK3915393 20 mg+ water on Day 1 in treatment Period 3; followed by a single oral dose of GSK3915393 20mg along with GFJ on Day 1 in treatment Period 4; further followed by a single oral dose of GSK3915393 20 mg along with ITZ in treatment Period 5. There was a washout period of 6 days between treatment Periods 1 and 2, washout period of 24 days between treatment periods 2 and 3, washout period of 10 days between treatment periods 3 and 4 and washout period of 13 days between treatment periods 4 and 5. There was a follow-up of 14 days.
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|---|---|---|---|---|---|---|---|---|---|---|
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Part A: Washout Period 1(Up to Day 20)
Physician Decision
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Part B: Up to Day 14
Adverse Event
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Part C: Washout Period 1 (Up to Day 6)
Adverse Event
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0
|
0
|
0
|
1
|
|
Part C: Washout Period 3 (Up to Day10)
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Part C: Washout Period 4 (Up to Day 13)
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Part C: Period 5 (Day 1)
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and to Evaluate the Interaction Between GSK3915393 and Grapefruit Juice and Itraconazole
Baseline characteristics by cohort
| Measure |
PartA: Placebo/GSK3915393 60mg/100mcg IV/160mg
n=4 Participants
Participants in Part A received a single oral dose of Placebo on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 milligrams (mg) on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 micrograms (mcg) intravenous (IV) on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4. Participants were dosed in the fed state. There was a washout period of 20 days between periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
|
Part A: GSK3915393 15mg/Placebo/100mcg IV/160mg
n=4 Participants
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of placebo on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160mg on Day 1 in treatment Period 4. Participants were dose in the fed state. There was a washout period of 20 days between periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
|
Part A: GSK3915393 15mg/60mg/100mcg IV/Placebo
n=3 Participants
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of placebo on Day 1 in treatment Period 4. Participants were dosed in fed state. There was a washout period of 20 days between Periods 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment periods 3 and 4 was of 20 days. There was a follow-up period of 14 days.
|
Part A: GSK3915393 15mg/60mg/100mcg IV/160mg
n=3 Participants
Participants in Part A received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1; followed by a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2; followed by a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 3; further followed by a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4. Participants were dosed in fed state. There was a washout period of 20 days between Period 1 and 2, washout period between treatment 2 and 3 was of 12 days, washout period between treatment period 3 and 4 was of 20 days. There was follow-up period of 14 days.
|
Part B: Placebo
n=10 Participants
Participants received placebo matching with GSK3915393 as repeat oral dose for 14 days (dosing frequency twice a day \[BID\] or QD, matched to the frequency of dosing in the concurrent active treatment arm). The impact of food effect on pharmacokinetic (PK) of GSK3915393 was investigated following Ante-Meridiem (AM) dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 20 mg (BID)
n=10 Participants
Participants received GSK3915393 20 mg BID as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 80 mg (BID)
n=9 Participants
Participants received GSK3915393 80 mg BID as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 160 mg (QD)
n=9 Participants
Participants received GSK3915393 160 mg QD as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
PartC:GSK3915393 100mcg IV/100mcgIV+ITZ/20mg+GFJ/20+WTR/20+ITZ
n=6 Participants
Participants in Part C received a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 1; followed by a single dose of GSK3915393 100mcg IV along with Itraconazole (ITZ) on Day 1 in treatment Period 2; followed by a single oral dose of GSK3915393 20 mg along with grapefruit juice (GFJ) on Day 1 in treatment Period 3; followed by a single oral dose of GSK3915393 20mg along with water (WTR) on Day 1 in treatment Period 4; further followed by a single oral dose of GSK3915393 20 mg along with ITZ in treatment Period 5. There was a washout period of 6 days between treatment Periods 1 and 2, washout period of 24 days between treatment periods 2 and 3, washout period of 10 days between treatment periods 3 and 4 and washout period of 13 days between treatment periods 4 and 5. There was a follow-up of 14 days.
|
Part C:GSK3915393 100mg IV/100mcgIV+ITZ/20mg+WTR/20+GFJ/20+ITZ
n=7 Participants
Participants in Part C received a single dose of GSK3915393 100 mcg IV on Day 1 in treatment Period 1; followed by a single dose of GSK3915393 100 mcg IV along with ITZ on Day 1 in treatment Period 2; followed by a single oral dose of GSK3915393 20 mg+ water on Day 1 in treatment Period 3; followed by a single oral dose of GSK3915393 20mg along with GFJ on Day 1 in treatment Period 4; further followed by a single oral dose of GSK3915393 20 mg along with ITZ in treatment Period 5. There was a washout period of 6 days between treatment Periods 1 and 2, washout period of 24 days between treatment periods 2 and 3, washout period of 10 days between treatment periods 3 and 4 and washout period of 13 days between treatment periods 4 and 5. There was a follow-up of 14 days.
|
Total
n=65 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Customized
<=18 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
|
Age, Customized
Between 19 and 65 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
10 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
9 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
7 Participants
n=42 Participants
|
64 Participants
n=42 Participants
|
|
Age, Customized
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
3 Participants
n=24 Participants
|
2 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
15 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
9 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
6 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
5 Participants
n=42 Participants
|
50 Participants
n=42 Participants
|
|
Race/Ethnicity, Customized
ASIAN - SOUTH EAST ASIAN HERITAGE
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
3 Participants
n=42 Participants
|
|
Race/Ethnicity, Customized
BLACK OR AFRICAN AMERICAN
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
1 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
8 Participants
n=42 Participants
|
|
Race/Ethnicity, Customized
WHITE -WHITE/CAUCASIAN/EUROPEAN HERITAGE
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
9 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
8 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
49 Participants
n=42 Participants
|
|
Race/Ethnicity, Customized
MIXED RACE
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
|
Race/Ethnicity, Customized
ASIAN -CENTRAL/SOUTH ASIAN HERITAGE
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
|
Race/Ethnicity, Customized
ASIAN -EAST ASIAN HERITAGE
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population comprised of all randomized participants who received at least one dose of study treatment.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With All Non-serious Adverse Events (AEs) and Serious AEs (SAEs) Following Administration of Oral Dose
All non-serious AEs
|
1 Participants
|
2 Participants
|
3 Participants
|
1 Participants
|
—
|
|
Part A: Number of Participants With All Non-serious Adverse Events (AEs) and Serious AEs (SAEs) Following Administration of Oral Dose
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs were presented.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Treatment-related AEs Following Administration of Oral Dose
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With All Non-serious AEs and SAEs
All non-serious AEs
|
3 Participants
|
5 Participants
|
1 Participants
|
5 Participants
|
—
|
|
Part B: Number of Participants With All Non-serious AEs and SAEs
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs are presented.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With Treatment-related AEs
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population.
Blood samples were collected for analysis of chemistry parameters. PCI ranges were \>=2\*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase \[ALT\]), \>=2\*ULN (U/L) (Aspartate Aminotransferase (\[AST\]), \>=2\*ULN (Alkaline Phosphatase \[ALP\]) (U/L), \>=1.5\*ULN (micromoles per liter) (bilirubin), \<2 or \>2.75 millimoles/liter (L) (mmol/L)(calcium), \<3 or \>11 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), \<130 or \>150 mmol/L (sodium),\<50 or \>85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
ALT: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
ALT: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
ALT: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
AST: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
AST: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
AST: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
ALP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
ALP: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
ALP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Bilirubin: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Bilirubin: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
8 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Bilirubin: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Calcium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Calcium: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Calcium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Glucose: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Glucose: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Glucose: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Potassium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Potassium: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Potassium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Protein: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Protein: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Protein: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Sodium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Sodium: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Sodium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population.
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline \> 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as within (w/in) range.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
W/in Range
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Increase of PCI
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population.
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High \>10.5 mmol/L. Participants were counted in worst case category that their value changes to (within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population.
Blood samples were collected for analysis of hematology parameters. PCI ranges were \>1\*10\^9 cell per liter (cells/L) (eosinophils), \<0.2 or \>0.54 proportion of red blood cells in blood (hematocrit), \<80 or \>180 grams per liter(g/L) (hemoglobin), \<3 or \>20 x10\^9 cells/L (leukocytes), \<0.8\*10\^9 cells/L (lymphocytes), \<1.5 or \>16\*10\^9 cells/L (neutrophils) and \<100 or \>550\*10\^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example \[e.g.\], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Eosinophils: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Eosinophils: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Eosinophils: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Hematocrit: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Hematocrit: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Hematocrit: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Hemoglobin: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Hemoglobin: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Hemoglobin: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Leukocytes: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Leukocytes: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Leukocytes: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Lymphocytes: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Lymphocytes: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Lymphocytes: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Neutrophils: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Neutrophils: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
8 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Neutrophils: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Platelets: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Platelets: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Platelets: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population.
Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury\[mmHg\]): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute):\<=8 (low) or \>20 (high) and body temperature (degrees Celsius) \<=35.5 (low) or \>38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
SBP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
SBP: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
SBP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
DBP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
DBP: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
DBP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
PR: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
PR: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
PR: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Body temperature: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Body temperature: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Body temperature: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
RR: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
RR: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
RR: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population.
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Following Administration of Oral Dose
Abnormal: Not Clinically Significant
|
2 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Following Administration of Oral Dose
Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 70 daysPopulation: Safety Population.
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Abnormal Physical Examination Findings Following Administration of Oral Dose
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
Blood samples were collected for analysis of chemistry parameters. PCI ranges were \>=2\*ULN (U/L)(ALT), \>=2\*ULN (U/L) (AST), \>=2\*ULN (ALP) (U/L), \>=1.5\*ULN (micromoles per liter) (bilirubin), \<2 or \>2.75 millimoles/liter (L) (mmol/L)(calcium), \<3 or \>11 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), \<130 or \>150 mmol/L (sodium),\<50 or \>85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Sodium: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Sodium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Glucose: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
ALT: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
ALT: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
ALT: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
AST: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
AST: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
8 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
AST: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
ALP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
ALP: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
ALP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Bilirubin: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Bilirubin: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Bilirubin: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Calcium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Calcium: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Calcium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Glucose: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Glucose: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Potassium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Potassium: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Potassium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Protein: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Protein: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Protein: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Sodium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High \>10.5 mmol/L. Participants were counted in worst case category that their value changes to (within \[w/in\] range or NC, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
To W/in Range or No Change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline \> 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range. Participants whose laboratory value became within range, were recorded in 'To within Range' category.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose
W/in Range
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose
Increase of PCI
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
Blood samples were collected for analysis of hematology parameters. PCI ranges were 1\*10\^9 cell per liter (cells/L) (eosinophils), \<0.2 or \>0.54 proportion of red blood cells in blood (hematocrit), \<80 or \>180 grams per liter(g/L) (hemoglobin), \<3 or \>20 x10\^9 cells/L (leukocytes), \<0.8\*10\^9 cells/L (lymphocytes), \<1.5 or \>16\*10\^9 cells/L (neutrophils) and \<100 or \>550\*10\^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example \[e.g.\], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Eosinophils: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Eosinophils: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Eosinophils: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Hematocrit: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Hematocrit: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Hematocrit: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Hemoglobin: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Hemoglobin: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Hemoglobin: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Leukocytes: To Low
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Leukocytes: To w/in Range or No change
|
10 Participants
|
10 Participants
|
8 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Leukocytes: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Lymphocytes: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Lymphocytes: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Lymphocytes: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Neutrophils: To Low
|
0 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Neutrophils: To w/in Range or No change
|
10 Participants
|
9 Participants
|
7 Participants
|
7 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Neutrophils: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Platelets: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Platelets: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Platelets: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute):\<=8 (low) or \>20 (high) and body temperature (degrees Celsius) \<=35.5 (low) or \>38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
SBP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
SBP: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
SBP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
DBP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
DBP: To w/in Range or No change
|
10 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
DBP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
PR: To Low
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
PR: To w/in Range or No change
|
9 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
PR: To High
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Body temperature: To Low
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Body temperature: To w/in Range or No change
|
10 Participants
|
9 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Body temperature: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
RR: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
RR: To w/in Range or No change
|
9 Participants
|
10 Participants
|
9 Participants
|
9 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
RR: To High
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Repeat Oral Dose of GSK3915393
Abnormal: Not Clinically Significant
|
3 Participants
|
5 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Repeat Oral Dose of GSK3915393
Clinically Significant
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: Safety Population.
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Number of Participants With Abnormal Physical Examination Findings Following Administration of Repeat Oral Dose of GSK3915393
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dosePopulation: Pharmacokinetic Population comprised of all participants in the safety population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Maximum Observed Plasma Drug Concentration (Cmax) Following IV Dose of GSK3915393
|
4.7220 Nanogram per milliliter
Geometric Coefficient of Variation 36.38
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Cmax of GSK3915393 Following IV Dose of GSK3915393+ITZ
|
7.8839 Nanogram per milliliter
Geometric Coefficient of Variation 23.80
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Cmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Cmax Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
|
145.5638 Nanogram per milliliter
Geometric Coefficient of Variation 63.79
|
145.0510 Nanogram per milliliter
Geometric Coefficient of Variation 46.66
|
982.5433 Nanogram per milliliter
Geometric Coefficient of Variation 33.02
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Time to Maximum Observed Plasma Drug Concentration (Tmax) Following IV Dose of GSK3915393
|
0.98 Hour
Interval 0.67 to 0.98
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Tmax of GSK3915393 Following IV Dose of GSK3915393+ITZ
|
0.98 Hour
Interval 0.98 to 1.0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Tmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Tmax of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
|
0.67 Hour
Interval 0.33 to 1.5
|
1.50 Hour
Interval 0.67 to 2.02
|
1.25 Hour
Interval 0.67 to 2.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Area Under Curve up to the Last Measurable Concentration (AUCLST[0-10]) Following IV Dose of GSK3915393
|
5.0061 Nanogram*hour per milliliter
Geometric Coefficient of Variation 41.94
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: AUCLST(0-24) of GSK3915393 Following IV Dose of GSK3915393+ITZ
|
13.3393 Nanogram*hour per milliliter
Geometric Coefficient of Variation 32.67
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: AUCLST(0-24) of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
|
153.8368 Nanogram*hour per milliliter
Geometric Coefficient of Variation 60.22
|
223.1288 Nanogram*hour per milliliter
Geometric Coefficient of Variation 52.85
|
2129.2407 Nanogram*hour per milliliter
Geometric Coefficient of Variation 39.04
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: AUC From Time Zero to Infinity (AUC[0-inf]) Following IV Dose of GSK3915393
|
5.0325 Nanogram*hour per milliliter
Geometric Coefficient of Variation 41.95
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: AUC(0-inf) of GSK3915393 Following IV Dose of GSK3915393+ITZ
|
13.4250 Nanogram*hour per milliliter
Geometric Coefficient of Variation 32.63
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. AUC(0-inf) was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: AUC(0-inf) of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
|
155.5203 Nanogram*hour per milliliter
Geometric Coefficient of Variation 59.89
|
225.0856 Nanogram*hour per milliliter
Geometric Coefficient of Variation 52.73
|
2141.8345 Nanogram*hour per milliliter
Geometric Coefficient of Variation 39.15
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Apparent Terminal Half-life (t1/2) of GSK3915393 Following IV Dose of GSK3915393
|
NA Hours
NA indicates that t1/2 cannot be calculated due to insufficient number of quantifiable pharmacokinetic (PK) values in the terminal phase
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: t1/2 of GSK3915393 Following IV Dose of GSK3915393+ITZ
|
NA Hour
NA indicates that t1/2 cannot be calculated due to insufficient number of quantifiable PK values in the terminal phase
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. t1/2 was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=10 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: t1/2 of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
|
NA Hours
NA indicates that t1/2 cannot be calculated due to insufficient number of quantifiable PK values in the terminal phase
|
NA Hours
NA indicates that t1/2 cannot be calculated due to insufficient number of quantifiable PK values in the terminal phase
|
NA Hours
NA indicates that t1/2 cannot be calculated due to insufficient number of quantifiable PK values in the terminal phase
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Cmax Following Single Oral Dose of GSK3915393
|
58.7910 Nanogram per milliliter
Geometric Coefficient of Variation 71.78
|
235.4331 Nanogram per milliliter
Geometric Coefficient of Variation 82.49
|
1246.2994 Nanogram per milliliter
Geometric Coefficient of Variation 54.12
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Cmax Following Single IV Dose of GSK3915393
|
4.3979 Nanogram per milliliter
Geometric Coefficient of Variation 35.65
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Tmax Following Single Oral Dose of GSK3915393
|
1.50 Hour
Interval 1.0 to 2.0
|
1.52 Hour
Interval 0.68 to 3.0
|
1.50 Hour
Interval 0.33 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Tmax Following IV Dose of GSK3915393
|
0.98 Hour
Interval 0.33 to 0.98
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, and 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: AUCLST(0-24) Following Single Oral Dose of GSK3915393
|
113.7272 Nanogram*hour per milliliter
Geometric Coefficient of Variation 103.13
|
424.6809 Nanogram*hour per milliliter
Geometric Coefficient of Variation 52.89
|
2221.3816 Nanogram*hour per milliliter
Geometric Coefficient of Variation 55.49
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: AUCLST(0-6) Following Single IV Dose of GSK3915393
|
4.4466 Nanogram*hour per milliliter
Geometric Coefficient of Variation 31.95
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: AUC(0-inf) Following Single Oral Dose of GSK3915393
|
116.5279 Nanogram*hour per milliliter
Geometric Coefficient of Variation 101.68
|
431.3298 Nanogram*hour per milliliter
Geometric Coefficient of Variation 51.93
|
2235.3991 Nanogram*hour per milliliter
Geometric Coefficient of Variation 55.18
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: AUC(0-inf) Following Single IV Dose of GSK3915393
|
4.4790 Nanogram*hour per milliliter
Geometric Coefficient of Variation 32.03
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: t1/2 Following Single IV Dose of GSK3915393 100 mcg IV
|
NA Hour
NA indicates that t1/2 cannot be calculated due to insufficient number of quantifiable PK values in the terminal phase
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Clearance (CL) Following Single IV Dose of GSK3915393
|
22.7675 Liters per hour
Geometric Coefficient of Variation 31.56
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Volume of Distribution (Vd) Following Single IV Dose of GSK3915393
|
30.7890 Liters
Geometric Coefficient of Variation 27.51
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. It was expressed as ratio was calculated as (AUC\[0-inf\] for oral divided by oral dose) divided by (AUC\[0-inf\] for IV/dose given as IV).
Outcome measures
| Measure |
Part A: Placebo
n=8 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Absolute Bioavailability (F) Following Single Oral Dose of GSK3915393
|
0.20 Ratio
Geometric Coefficient of Variation 69.6
|
0.18 Ratio
Geometric Coefficient of Variation 40.7
|
0.29 Ratio
Geometric Coefficient of Variation 38.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute).
Outcome measures
| Measure |
Part A: Placebo
n=8 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Fraction of Drug Escaping Hepatic Metabolism (FH) Following Single Oral Dose of GSK3915393
|
0.5367 Ratio
Interval 0.435 to 0.699
|
0.4617 Ratio
Interval 0.384 to 0.69
|
0.5107 Ratio
Interval 0.384 to 0.699
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. Product of FA\*FG was calculated as: (absolute bioavailability \[F\] divided by fraction of drug escaping hepatic metabolism \[FH\]).
Outcome measures
| Measure |
Part A: Placebo
n=8 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Product of Fraction of Drug Absorbed and Fraction of Drug Escaping Gut Metabolism (FA*FG) Following Oral Dose of GSK3915393
|
0.3062 Ratio
Interval 0.191 to 1.454
|
0.3814 Ratio
Interval 0.238 to 0.639
|
0.5563 Ratio
Interval 0.328 to 1.173
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Safety Population.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With All Non-serious AEs and SAEs Following Administration Administration of IV Dose of GSK3915393
All non-serious AEs
|
4 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With All Non-serious AEs and SAEs Following Administration Administration of IV Dose of GSK3915393
SAEs
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Safety Population.
Blood samples were collected for analysis of chemistry parameters. PCI ranges were \>=2\*ULN (U/L)(ALT), \>=2\*ULN (U/L) (AST), \>=2\*ULN (ALP) (U/L), \>=1.5\*ULN (micromoles per liter) (bilirubin), \<2 or \>2.75 millimoles/liter (L) (mmol/L)(calcium), \<3 or \>11 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), \<130 or \>150 mmol/L (sodium),\<50 or \>85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
ALT: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
ALT: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
ALT: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
AST: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
AST: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
AST: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
ALP: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
ALP: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
ALP: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Bilirubin: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Bilirubin: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Bilirubin: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Calcium: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Calcium: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Calcium: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Glucose: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Glucose: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Glucose: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Potassium: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Potassium: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Potassium: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Protein: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Protein: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Protein: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Sodium: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Sodium: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Sodium: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Safety Population.
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline \>44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
W/in Range
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Increase of PCI
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Safety Population.
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High \>10.5 mmol/L. Participants were counted in worst case category that their value changes to (within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
To High
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Safety Population.
Blood samples were collected for analysis of hematology parameters. PCI ranges were \>1\*10\^9 cell per liter (cells/L) (eosinophils), \<0.2 or \>0.54 proportion of red blood cells in blood (hematocrit), \<80 or \>180 grams per liter(g/L) (hemoglobin), \<3 or \>20 x10\^9 cells/L (leukocytes), \<0.8\*10\^9 cells/L (lymphocytes), \<1.5 or \>16\*10\^9 cells/L (neutrophils) and \<100 or \>550\*10\^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example \[e.g.\], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Eosinophils: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Eosinophils: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Eosinophils: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Hematocrit: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Hematocrit: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Hematocrit: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Hemoglobin: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Hemoglobin: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Hemoglobin: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Leukocytes: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Leukocytes: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Leukocytes: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Lymphocytes: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Lymphocytes: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Lymphocytes: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Neutrophils: To Low
|
1 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Neutrophils: To w/in Range or No change
|
11 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Neutrophils: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Platelets: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Platelets: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Platelets: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Safety Population.
Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute):\<=8 (low) or \>20 (high) and body temperature (degrees Celsius) \<=35.5 (low) or \>38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
SBP: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
SBP: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
SBP: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
DBP: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
DBP: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
DBP: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
PR: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
PR: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
PR: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
Body temperature: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
Body temperature: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
Body temperature: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
RR: To Low
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
RR: To w/in Range or No change
|
12 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
RR: To High
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Safety Population.
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of IV Dose of GSK3915393
Abnormal: Not Clinically Significant
|
7 Participants
|
—
|
—
|
—
|
—
|
|
Part A: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of IV Dose of GSK3915393
Clinically Significant
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: Safety Population.
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part A: Number of Participants With Abnormal Physical Examination Findings Following Administration of IV Dose of GSK3915393
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Cmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14
Day 1, n=10, 9, 9
|
64.7843 Nanograms per milliliter
Geometric Coefficient of Variation 45.50
|
408.5572 Nanograms per milliliter
Geometric Coefficient of Variation 107.00
|
823.7704 Nanograms per milliliter
Geometric Coefficient of Variation 42.34
|
—
|
—
|
|
Part B: Cmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14
Day 14, n=9, 9, 9
|
95.4416 Nanograms per milliliter
Geometric Coefficient of Variation 93.47
|
820.5354 Nanograms per milliliter
Geometric Coefficient of Variation 67.59
|
1710.7385 Nanograms per milliliter
Geometric Coefficient of Variation 48.78
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Cmax(10-24) Following Repeat Dose 20 mg and 80 mg of GSK3915393
Day 1, n=10, 9
|
32.2127 Nanograms per milliliter
Geometric Coefficient of Variation 48.16
|
338.2996 Nanograms per milliliter
Geometric Coefficient of Variation 85.59
|
—
|
—
|
—
|
|
Part B: Cmax(10-24) Following Repeat Dose 20 mg and 80 mg of GSK3915393
Day 14, n=9, 9
|
62.0235 Nanograms per milliliter
Geometric Coefficient of Variation 114.26
|
931.2098 Nanograms per milliliter
Geometric Coefficient of Variation 62.68
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: 10, 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Cmax(10-24) Following Dose 160 mg (QD) of GSK3915393
Day 1
|
NA Nanograms per milliliter
Geometric Coefficient of Variation NA
NA indicates data is not available as Cmax(10-24) could not be considered reliable because only a single PK time point was collected beyond 10 hours post-dose for 160 mg once daily on Day 1
|
—
|
—
|
—
|
—
|
|
Part B: Cmax(10-24) Following Dose 160 mg (QD) of GSK3915393
Day 14
|
NA Nanograms per milliliter
Geometric Coefficient of Variation NA
NA indicates data is not available as Cmax(10-24) could not be considered reliable because only a single PK time point was collected beyond 10 hours post-dose for 160 mg once daily on Day 14
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Tmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14
Day 1, n=10, 9, 9
|
1.2583 Hour
Interval 1.0 to 3.017
|
1.0167 Hour
Interval 0.667 to 3.0
|
1.5000 Hour
Interval 0.667 to 3.017
|
—
|
—
|
|
Part B: Tmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14
Day 14, n=9, 9, 9
|
1.5000 Hour
Interval 0.667 to 3.0
|
0.7500 Hour
Interval 0.333 to 1.0
|
0.6833 Hour
Interval 0.3 to 1.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Tmax(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Day 1, n=10, 9
|
2.0000 Hour
Interval 2.0 to 4.0
|
2.0000 Hour
Interval 0.667 to 3.0
|
—
|
—
|
—
|
|
Part B: Tmax(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Day 14, n=9, 9
|
2.0000 Hour
Interval 0.667 to 6.133
|
0.6667 Hour
Interval 0.35 to 0.7
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: 10, 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Tmax(10-24) Following Dose 160 mg (QD) of GSK3915393
Day 1
|
NA Hour
NA indicates data is not available as Tmax(10-24) could not be considered reliable because only a single PK time point was collected beyond 10 hours post-dose for 160 mg once daily on Day 1
|
—
|
—
|
—
|
—
|
|
Part B: Tmax(10-24) Following Dose 160 mg (QD) of GSK3915393
Day 14
|
NA Hour
NA indicates data is not available as Tmax(10-24) could not be considered reliable because only a single PK time point was collected beyond 10 hours post-dose for 160 mg once daily on Day 14
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: AUCLST(0-10) Following Dosing of GSK3915393
Day 1, n=10, 9, 9
|
90.7283 Nanograms*hour per milliliter
Geometric Coefficient of Variation 47.48
|
570.8621 Nanograms*hour per milliliter
Geometric Coefficient of Variation 73.35
|
1268.9518 Nanograms*hour per milliliter
Geometric Coefficient of Variation 34.85
|
—
|
—
|
|
Part B: AUCLST(0-10) Following Dosing of GSK3915393
Day 14, n=9, 9, 9
|
173.2096 Nanograms*hour per milliliter
Geometric Coefficient of Variation 63.74
|
873.9352 Nanograms*hour per milliliter
Geometric Coefficient of Variation 44.84
|
1670.9421 Nanograms*hour per milliliter
Geometric Coefficient of Variation 36.52
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: Pre-dose, 20 minutes, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: AUCLST(0-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Day 1, n=10, 9
|
193.1524 Nanograms*hour per milliliter
Geometric Coefficient of Variation 48.59
|
1242.5500 Nanograms*hour per milliliter
Geometric Coefficient of Variation 67.19
|
—
|
—
|
—
|
|
Part B: AUCLST(0-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Day 14, n=9, 9
|
342.1653 Nanograms*hour per milliliter
Geometric Coefficient of Variation 62.25
|
1856.9207 Nanograms*hour per milliliter
Geometric Coefficient of Variation 45.22
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: Pre-dose, 20 minutes, 40 minutess, 1, 1.5, 2, 3 ,4, 6, 10 and 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: AUCLST(0-24) Following Dose of GSK3915393 160 mg (QD)
Day 1
|
1314.7399 Nanograms*hour per milliliter
Geometric Coefficient of Variation 34.62
|
—
|
—
|
—
|
—
|
|
Part B: AUCLST(0-24) Following Dose of GSK3915393 160 mg (QD)
Day 14
|
1738.3433 Nanograms*hour per milliliter
Geometric Coefficient of Variation 36.02
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=8 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: AUC(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Day 1
|
115.2199 Nanograms*hour per milliliter
Geometric Coefficient of Variation 52.85
|
666.5290 Nanograms*hour per milliliter
Geometric Coefficient of Variation 62.91
|
—
|
—
|
—
|
|
Part B: AUC(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Day 14
|
189.9773 Nanograms*hour per milliliter
Geometric Coefficient of Variation 47.30
|
959.7659 Nanograms*hour per milliliter
Geometric Coefficient of Variation 49.53
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 14: 10 and 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: AUC(10-24) Following Repeat Dose of GSK3915393 160 mg (QD)
Day 1
|
NA Nanograms*hour per milliliter
Geometric Coefficient of Variation NA
NA indicates data is not available as AUC(10-24) could not be considered reliable because only a single PK time point was collected beyond 10 hours post-dose for 160 mg once daily on Day 1
|
—
|
—
|
—
|
—
|
|
Part B: AUC(10-24) Following Repeat Dose of GSK3915393 160 mg (QD)
Day 14
|
NA Nanograms*hour per milliliter
Geometric Coefficient of Variation NA
NA indicates data is not available as AUC(10-24) could not be considered reliable because only a single PK time point was collected beyond 10 hours post-dose for 160 mg once daily on Day 14
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6 and 10 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Cmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 3, n=10, 9, 9
|
125.5298 Nanograms*hour per milliliter
Geometric Coefficient of Variation 76.57
|
819.8381 Nanograms*hour per milliliter
Geometric Coefficient of Variation 99.60
|
1324.4415 Nanograms*hour per milliliter
Geometric Coefficient of Variation 25.48
|
—
|
—
|
|
Part B: Cmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 5, n= 10, 9, 9
|
56.9187 Nanograms*hour per milliliter
Geometric Coefficient of Variation 54.99
|
235.7608 Nanograms*hour per milliliter
Geometric Coefficient of Variation 75.63
|
550.0071 Nanograms*hour per milliliter
Geometric Coefficient of Variation 75.02
|
—
|
—
|
|
Part B: Cmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 7, n= 9, 9, 9
|
77.0364 Nanograms*hour per milliliter
Geometric Coefficient of Variation 48.64
|
355.0055 Nanograms*hour per milliliter
Geometric Coefficient of Variation 104.08
|
805.5202 Nanograms*hour per milliliter
Geometric Coefficient of Variation 28.13
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6 and 10 hours post-dosePopulation: Pharmacokinetic Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Tmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 3, n=10, 9, 9
|
0.6667 Hour
Interval 0.333 to 1.0
|
1.0000 Hour
Interval 0.333 to 2.033
|
1.0000 Hour
Interval 0.667 to 2.0
|
—
|
—
|
|
Part B: Tmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 5, n= 10, 9, 9
|
1.5000 Hour
Interval 0.667 to 3.0
|
1.5167 Hour
Interval 1.0 to 4.0
|
3.0000 Hour
Interval 1.0 to 4.0
|
—
|
—
|
|
Part B: Tmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 7, n= 9, 9, 9
|
1.5000 Hour
Interval 0.667 to 3.0
|
1.5000 Hour
Interval 1.0 to 3.0
|
1.5000 Hour
Interval 0.717 to 2.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6 and 10 hours post-dosePopulation: Pharmacokinetic Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed (represented by n=X in category titles).
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=10 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: AUCLST(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 7, n= 9, 9, 9
|
135.3659 Nanogram*hour per milliliter
Geometric Coefficient of Variation 49.21
|
754.3745 Nanogram*hour per milliliter
Geometric Coefficient of Variation 69.11
|
1551.1980 Nanogram*hour per milliliter
Geometric Coefficient of Variation 21.66
|
—
|
—
|
|
Part B: AUCLST(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 3, n=10, 9, 9
|
115.6796 Nanogram*hour per milliliter
Geometric Coefficient of Variation 60.32
|
883.5828 Nanogram*hour per milliliter
Geometric Coefficient of Variation 75.58
|
1571.0637 Nanogram*hour per milliliter
Geometric Coefficient of Variation 25.05
|
—
|
—
|
|
Part B: AUCLST(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Day 5, n= 10, 9, 9
|
120.0480 Nanogram*hour per milliliter
Geometric Coefficient of Variation 56.72
|
698.9908 Nanogram*hour per milliliter
Geometric Coefficient of Variation 61.80
|
1320.6847 Nanogram*hour per milliliter
Geometric Coefficient of Variation 25.74
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 14: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6, 10, 10 hour 20 minutes, 10 hours 40 minutes, 12, 12.5, 13, 14, 16 and 24 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Trough Concentration (Ctau) Following Dose of 20 mg BID and 80 mg BID of GSK3915393 on Day 14
|
1.8808 Nanograms per milliliter
Standard Deviation 1.35678
|
3.3181 Nanograms per milliliter
Standard Deviation 2.36137
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 14: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6, 10, and 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Outcome measures
| Measure |
Part A: Placebo
n=9 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part B: Trough Concentration (Ctau) Following Dose of 160 mg of GSK3915393 on Day 14
|
2.5423 Nanograms per milliliter
Standard Deviation 1.75889
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With All Non-serious AEs and SAEs
All non-serious AEs
|
5 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Part C: Number of Participants With All Non-serious AEs and SAEs
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs are presented.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With Treatment-related AEs Following Dose of GSK3915393
|
3 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
Blood samples were collected for analysis of chemistry parameters. PCI ranges were \>=2\*ULN (U/L)(ALT), \>=2\*ULN (U/L) (AST), \>=2\*ULN (ALP) (U/L), \>=1.5\*ULN (micromoles per liter) (bilirubin), \<2 or \>2.75 millimoles/liter (L) (mmol/L)(calcium), \<3 or \>11 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), \<130 or \>150 mmol/L (sodium),\<50 or \>85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Bilirubin: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Calcium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
ALT: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
ALT: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
ALT: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
AST: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
ALP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
AST: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
ALP: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
ALP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
AST: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Bilirubin: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Bilirubin: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Calcium: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
11 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Calcium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Glucose: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Glucose: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Glucose: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Potassium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Potassium: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Potassium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Protein: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Protein: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Protein: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Sodium: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Sodium: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Sodium: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline \> 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range. Participants whose laboratory value became within range, were recorded in 'To within Range' category.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With Worst Case Chemistry Results: Creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Increase of PCI
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results: Creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
W/in Range
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High \>10.5 mmol/L. Participants were counted in worst case category that their value changes to ( within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With Worst Case Chemistry Results: Urea by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
To W/in Range or No Change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Chemistry Results: Urea by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
Blood samples were collected for analysis of hematology parameters. PCI ranges were 1\*10\^9 cell per liter (cells/L) (eosinophils), \<0.2 or \>0.54 proportion of red blood cells in blood (hematocrit), \<80 or \>180 grams per liter(g/L) (hemoglobin), \<3 or \>20 x10\^9 cells/L (leukocytes), \<0.8\*10\^9 cells/L (lymphocytes), \<1.5 or \>16\*10\^9 cells/L (neutrophils) and \<100 or \>550\*10\^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example \[e.g.\], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Eosinophils: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Eosinophils: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Eosinophils: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Hematocrit: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Hematocrit: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Hematocrit: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Hemoglobin: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Hemoglobin: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Hemoglobin: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Leukocytes: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Leukocytes: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Leukocytes: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Lymphocytes: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Lymphocytes: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Lymphocytes: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Neutrophils: To Low
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Neutrophils: To w/in Range or No change
|
11 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Neutrophils: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Platelets: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Platelets: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Platelets: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute):\<=8 (low) or \>20 (high) and body temperature (degrees Celsius) \<=35.5 (low) or \>38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
SBP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
SBP: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
SBP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
DBP: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
DBP: To w/in Range or No change
|
12 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
DBP: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
PR: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
PR: To w/in Range or No change
|
11 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
PR: To High
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Temperature: To Low
|
0 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Temperature: To w/in Range or No change
|
12 Participants
|
10 Participants
|
9 Participants
|
11 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Temperature: To High
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
RR: To Low
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
RR: To w/in Range or No change
|
11 Participants
|
11 Participants
|
11 Participants
|
12 Participants
|
10 Participants
|
|
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
RR: To High
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of GSK3915393
Abnormal: Not Clinically Significant
|
2 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of GSK3915393
Clinically Significant
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 72 daysPopulation: Safety Population.
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Outcome measures
| Measure |
Part A: Placebo
n=12 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=11 Participants
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=12 Participants
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
n=10 Participants
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Number of Participants With Abnormal Physical Examination Findings Following Administration of GSK3915393
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hour 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute)
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Fraction of Drug Escaping Hepatic Metabolism (FH) Following IV Dose of GSK3915393
|
0.6525 Ratio
Interval 0.435 to 0.856
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hour 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus Hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute)
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: FH Following IV Administration of GSK3915393+ITZ
|
0.8717 Ratio
Interval 0.78 to 0.905
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FG was expressed as ratio and calculated as: AUC of GSK3915393+water divided by AUC of GSK3915393+GFJ.
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Fraction of Drug Escaping Gut Metabolism (FG) Following Oral Administration of GSK3915393+Water
|
NA Ratio
NA indicates data is not available as estimates for FA and FG generated by analysis of the GFJ interaction study were inconsistent with pharmacokinetic data from the rest of the study and are thus not considered reliable.
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours post-dosePopulation: Pharmacokinetic Population.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FA was expressed as ratio was calculated as absolute bioavailability (F) divided by the product of fraction of drug escaping hepatic metabolism (FH) and fraction of drug escaping gut metabolism (FG).
Outcome measures
| Measure |
Part A: Placebo
n=11 Participants
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part C: SK3915393 20 mg+ITZ
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|
|
Part C: Fraction of Drug Absorbed (FA) Following Oral Administration of GSK3915393+Water
|
NA Ratio
NA indicates data is not available as estimates for FA and FG generated by analysis of the GFJ interaction study were inconsistent with pharmacokinetic data from the rest of the study and are thus not considered reliable.
|
—
|
—
|
—
|
—
|
Adverse Events
Part A: Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part A: GSK3915393 15 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part A: GSK3915393 60 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part A: GSK3915393 160 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part A: GSK3915393 100 mcg IV
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part B: Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part B: GSK3915393 20 mg (BID)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Part B: GSK3915393 80 mg (BID)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part B: GSK3915393 160 mg (QD)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Part C: GSK3915393 100 mcg IV
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Part C: GSK3915393 100 mcg+ITZ
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part C: GSK3915393 20 mg+ Water
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part C: GSK3915393 20 mg+ GFJ
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part C: GSK3915393 20 mg+ ITZ
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part A: Placebo
n=9 participants at risk
Participants received a single oral dose of matching placebo on Day 1 in treatment Periods 1, 2 or 4.
|
Part A: GSK3915393 15 mg
n=9 participants at risk
Participants received a single oral dose of GSK3915393 15 mg on Day 1 in treatment Period 1.
|
Part A: GSK3915393 60 mg
n=9 participants at risk
Participants received a single oral dose of GSK3915393 60 mg on Day 1 in treatment Period 2.
|
Part A: GSK3915393 160 mg
n=9 participants at risk
Participants received a single oral dose of GSK3915393 160 mg on Day 1 in treatment Period 4.
|
Part A: GSK3915393 100 mcg IV
n=12 participants at risk
Participants received single dose of GSK3915393 100 mcg IV.
|
Part B: Placebo
n=10 participants at risk
Participants received placebo matching with GSK3915393 as repeat oral dose for 14 days (dosing frequency twice a day \[BID\] or QD, matched to the frequency of dosing in the concurrent active treatment arm). The impact of food effect on pharmacokinetic (PK) of GSK3915393 was investigated following Ante-Meridiem (AM) dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 20 mg (BID)
n=10 participants at risk
Participants received GSK3915393 20 mg BID as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 80 mg (BID)
n=9 participants at risk
Participants received GSK3915393 80 mg BID as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part B: GSK3915393 160 mg (QD)
n=9 participants at risk
Participants received GSK3915393 160 mg QD as repeat oral dose for 14 days. The impact of food effect on PK of GSK3915393 was investigated following AM dose on three days in all cohort (Day 3=fasted, Day 5= high fat breakfast, Day 7=standard breakfast).
|
Part C: GSK3915393 100 mcg IV
n=12 participants at risk
Participants received GSK3915393 100 mcg as IV dose.
|
Part C: GSK3915393 100 mcg+ITZ
n=11 participants at risk
Participants received GSK3915393 100 mcg as oral dose in combination with ITZ
|
Part C: GSK3915393 20 mg+ Water
n=11 participants at risk
Participants received GSK3915393 20 mg as oral dose in combination with water.
|
Part C: GSK3915393 20 mg+ GFJ
n=12 participants at risk
Participants received GSK3915393 20 mg as oral dose in combination with GFJ.
|
Part C: GSK3915393 20 mg+ ITZ
n=10 participants at risk
Participants received GSK3915393 20 mg as oral dose in combination with ITZ
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Nervous system disorders
Headache
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
16.7%
2/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
33.3%
3/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
25.0%
3/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
18.2%
2/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Nervous system disorders
Syncope
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Cardiac disorders
Palpitations
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Cardiac disorders
Nodal rhythm
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Gastrointestinal disorders
Abdominal tenderness
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Medical device site reaction
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Catheter site bruise
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Medical device site dermatitis
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Vessel puncture site bruise
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Catheter site pain
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Catheter site swelling
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Fatigue
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
General disorders
Infusion site pain
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Injury, poisoning and procedural complications
Exposure to SARS-CoV-2
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
11.1%
1/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Investigations
SARS-CoV-2 test positive
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
9.1%
1/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
8.3%
1/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
10.0%
1/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/9 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/11 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/12 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
0.00%
0/10 • All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C
All-cause mortality, all non-serious AEs and SAEs were collected in Safety population comprised of all randomized participants who received at least one dose of study treatment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial
- Publication restrictions are in place
Restriction type: OTHER