Trial Outcomes & Findings for First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants (NCT NCT03261401)
NCT ID: NCT03261401
Last Updated: 2023-10-16
Results Overview
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
88 participants
Primary outcome timeframe
Baseline up to Day 55
Results posted on
2023-10-16
Participant Flow
The study was planned to be conducted in 3 parts: Part A, B and C. Part B of the study was optional and sponsor decided not to perform part B of the study. In each cohort of Part A, participants were randomized in a 6:2 ratio to receive M5717 or matching placebo.
Participant milestones
| Measure |
Part A: Placebo (Pooled)
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 150 mg
Participants received single oral dose of 150 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 400 mg
Participants received single oral dose of 400 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 800 mg
Participants received single oral dose of 800 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
17
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
1
|
6
|
8
|
8
|
|
Overall Study
COMPLETED
|
17
|
6
|
6
|
6
|
6
|
5
|
6
|
6
|
6
|
1
|
6
|
8
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Part A: Placebo (Pooled)
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 150 mg
Participants received single oral dose of 150 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 400 mg
Participants received single oral dose of 400 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 800 mg
Participants received single oral dose of 800 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Participant Unable To Attend Final Visit
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants
Baseline characteristics by cohort
| Measure |
Part A: Placebo (Pooled)
n=17 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=6 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
n=1 Participants
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 150 mg
n=6 Participants
Participants received single oral dose of 150 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 400 mg
n=8 Participants
Participants received single oral dose of 400 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 800 mg
n=8 Participants
Participants received single oral dose of 800 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 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
|
2 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
|
2 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
5 Participants
n=36 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
6 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
5 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
8 Participants
n=36 Participants
|
83 Participants
n=36 Participants
|
|
Age, Categorical
>=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
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
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
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
6 Participants
n=24 Participants
|
6 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
8 Participants
n=42 Participants
|
8 Participants
n=36 Participants
|
88 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
1 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
2 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
12 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
5 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
5 Participants
n=24 Participants
|
5 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
5 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
8 Participants
n=36 Participants
|
76 Participants
n=36 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
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
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 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
|
2 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
6 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
2 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
|
3 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
8 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
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
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 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
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
4 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
5 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
8 Participants
n=36 Participants
|
66 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 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
|
1 Participants
n=115 Participants
|
1 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
3 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
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
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 55Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 or placebo for Part A).
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=17 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=6 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
n=1 Participants
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment
TEAEs Leading to Discontinuation
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment
TEAEs
|
13 Participants
|
6 Participants
|
5 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
4 Participants
|
5 Participants
|
6 Participants
|
1 Participants
|
|
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment
Serious TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 55Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 or placebo for Part A).
Laboratory assessments included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical significance was decided by the investigator.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=17 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=6 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
n=1 Participants
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Assessments
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 55Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 or placebo for Part A).
The 12-lead ECGs were recorded after the participants had rested for at least 5 minutes in supine position. Number of participants with clinically significant change from baseline in ECGs was reported. Clinical significance was decided by the investigator.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=17 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=6 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
n=1 Participants
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Number of Participants With Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 55Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 or placebo for Part A).
Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. Number of participants with clinically significant change from baseline in vital signs was reported. Clinical significance was decided by the investigator.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=17 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=6 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
n=1 Participants
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 22Population: Pharmacodynamic (PD) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PD and provided at least one (measurable) post-dose PD data. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure.
The parasite reduction ratio (PRR) of asexual parasites based on quantitative polymerase chain reaction (qPCR) after administration of M5717 is a mathematical representation of the ratio of the parasite density between drug administration and for a defined period of time. The PRR for asexual forms was estimated using the slope of the optimal fit of the log-linear relationship of the parasitemia decay; ie, the time point where steady exponential decay in parasitemia occurs which may happen after a lag-phase. Lag phase is defined as an initial period after dosing that precedes a steady exponential decline in the parasite count. It was observed that the decline of parasitemia had a biphasic profile, with the first phase, followed by a second phase (the main clearance phase).
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=7 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Parasite Reduction Ratio (PRR) Assessed Through Quantitative Polymerase Chain Reaction (qPCR) Analysis
First Phase
|
1.15 Ratio
Interval 0.59 to 2.25
|
1.73 Ratio
Interval 1.27 to 2.37
|
3.86 Ratio
Interval 2.9 to 5.13
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Parasite Reduction Ratio (PRR) Assessed Through Quantitative Polymerase Chain Reaction (qPCR) Analysis
Second Phase
|
12892 Ratio
Interval 3858.0 to 43081.0
|
5127 Ratio
Interval 1006.0 to 26132.0
|
436 Ratio
Interval 179.0 to 1061.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717,had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Maximum Observed Plasma Concentration (Cmax) of M5717
|
36.3 Nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 37.0
|
174 Nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 28.7
|
269 Nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 48.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The time to reach the maximum observed plasma concentration (tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M5717
|
3.75 Hours
Interval 1.0 to 12.0
|
2.01 Hours
Interval 1.0 to 8.0
|
2.00 Hours
Interval 1.5 to 6.02
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Lambda z determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Terminal Elimination Rate Constant (Lambda z) of M5717
|
0.00653 one per hour (1/hour)
Geometric Coefficient of Variation 19.4
|
0.00476 one per hour (1/hour)
Geometric Coefficient of Variation 14.9
|
0.00358 one per hour (1/hour)
Geometric Coefficient of Variation 20.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from the determination of the terminal first order (elimination) rate constant (lambda z). AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. Clastpred was the last predicted quantifiable concentration.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M5717
|
3100 Nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 41.0
|
10300 Nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 40.4
|
20000 Nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 37.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M5717
|
2680 ng*h/mL
Geometric Coefficient of Variation 44.9
|
9470 ng*h/mL
Geometric Coefficient of Variation 42.9
|
19200 ng*h/mL
Geometric Coefficient of Variation 38.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, and 144 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The area under the plasma concentration-time curve from time zero to 144 hours after dosing was reported. It is calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Area Under the Plasma Concentration-Time Curve From Time Zero to Time 144 Hours After Drug Administration (AUC0-144h) of M5717
|
1930 ng*h/mL
Geometric Coefficient of Variation 34.7
|
6260 ng*h/mL
Geometric Coefficient of Variation 35.1
|
10000 ng*h/mL
Geometric Coefficient of Variation 28.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
T1/2 was the time measured for the concentration to decrease by one half. T1/2 was calculated as natural log2 divided by lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Apparent Terminal Half Life (t1/2) of M5717
|
106 Hours
Geometric Coefficient of Variation 19.4
|
146 Hours
Geometric Coefficient of Variation 14.9
|
193 Hours
Geometric Coefficient of Variation 20.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for M5717, whereas AUC0-infinity is area under the plasma concentration-time curve from time zero (dosing time) extrapolated to infinity of unchanged drug calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-infinity calculated by Clastpred/lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log linear regression line for lambda z determination at which the measured plasma concentration is at or above lower limit of quantification.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Apparent Total Clearance (CL/f) of M5717
|
38.4 Liter per hour
Geometric Coefficient of Variation 41.0
|
31.1 Liter per hour
Geometric Coefficient of Variation 40.4
|
31.9 Liter per hour
Geometric Coefficient of Variation 37.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz/f = Dose/(AUC0-infinity multiply by Lambda z) following single dose.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Apparent Volume of Distribution During Terminal Phase (VZ/f) of M5717
|
5880 Liter
Geometric Coefficient of Variation 30.1
|
6530 Liter
Geometric Coefficient of Variation 28.7
|
8890 Liter
Geometric Coefficient of Variation 26.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Minimal inhibitory concentration (MIC), defined as the concentration at which the relative rate of change in parasitemia is equal to zero.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Time Above or Equal to the Predicted M5717 Minimum Inhibitory Concentration (MIC) of 3 ng/mL (t =>3 ng/mL)
|
314.55 Hours
Interval 213.06 to 392.65
|
518.50 Hours
Interval 390.7 to 827.08
|
809.12 Hours
Interval 495.92 to 1031.63
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Minimal parasiticidal concentration represents the lowest drug concentration value above which parasites decline at a maximal rate.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Time Above or Equal to the Predicted M5717 Minimum Parasiticidal Concentration (MPC) of 10 ng/mL (t =>10 ng/mL)
|
107.47 Hours
Interval 36.65 to 139.31
|
281.15 Hours
Interval 186.41 to 482.73
|
500.26 Hours
Interval 242.97 to 643.18
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Maximum Observed Plasma Concentration (Cmax) of M5717
|
7.50 ng/mL
Geometric Coefficient of Variation 54.3
|
14.9 ng/mL
Geometric Coefficient of Variation 19.7
|
35.7 ng/mL
Geometric Coefficient of Variation 41.3
|
146 ng/mL
Geometric Coefficient of Variation 37.9
|
267 ng/mL
Geometric Coefficient of Variation 25.4
|
642 ng/mL
Geometric Coefficient of Variation 53.2
|
988 ng/mL
Geometric Coefficient of Variation 40.3
|
1160 ng/mL
Geometric Coefficient of Variation 22.7
|
1240 ng/mL
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The time to reach the maximum observed plasma concentration (tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M5717
|
1.00 Hours
Interval 1.0 to 1.0
|
7.00 Hours
Interval 1.0 to 12.0
|
4.00 Hours
Interval 0.5 to 8.02
|
3.00 Hours
Interval 1.5 to 6.0
|
2.00 Hours
Interval 1.0 to 6.0
|
1.75 Hours
Interval 1.5 to 10.0
|
1.75 Hours
Interval 1.5 to 8.0
|
2.00 Hours
Interval 1.5 to 6.0
|
1.50 Hours
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Lambda z determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Terminal Elimination Rate Constant (Lambda z) of M5717
|
0.00523 one per hour (1/hour)
Geometric Coefficient of Variation 39.7
|
0.00523 one per hour (1/hour)
Geometric Coefficient of Variation 29.5
|
0.00478 one per hour (1/hour)
Geometric Coefficient of Variation 28.4
|
0.00447 one per hour (1/hour)
Geometric Coefficient of Variation 17.3
|
0.00382 one per hour (1/hour)
Geometric Coefficient of Variation 25.6
|
0.00411 one per hour (1/hour)
Geometric Coefficient of Variation 38.0
|
0.00386 one per hour (1/hour)
Geometric Coefficient of Variation 16.7
|
0.00383 one per hour (1/hour)
Geometric Coefficient of Variation 31.4
|
0.00493 one per hour (1/hour)
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
T1/2 was the time measured for the concentration to decrease by one half. T1/2 was calculated as natural log2 divided by lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Apparent Terminal Half Life (t1/2) of M5717
|
133 Hours
Geometric Coefficient of Variation 39.7
|
133 Hours
Geometric Coefficient of Variation 29.5
|
145 Hours
Geometric Coefficient of Variation 28.4
|
155 Hours
Geometric Coefficient of Variation 17.3
|
181 Hours
Geometric Coefficient of Variation 25.6
|
169 Hours
Geometric Coefficient of Variation 38.0
|
180 Hours
Geometric Coefficient of Variation 16.7
|
181 Hours
Geometric Coefficient of Variation 31.4
|
140 Hours
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from the determination of the terminal first order (elimination) rate constant (lambda z). AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. Clastpred was the last predicted quantifiable concentration.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M5717
|
997 ng*h/mL
Geometric Coefficient of Variation 23.9
|
1710 ng*h/mL
Geometric Coefficient of Variation 44.3
|
3500 ng*h/mL
Geometric Coefficient of Variation 28.1
|
10100 ng*h/mL
Geometric Coefficient of Variation 24.9
|
17500 ng*h/mL
Geometric Coefficient of Variation 29.7
|
28600 ng*h/mL
Geometric Coefficient of Variation 29.8
|
37800 ng*h/mL
Geometric Coefficient of Variation 28.2
|
52800 ng*h/mL
Geometric Coefficient of Variation 32.4
|
43000 ng*h/mL
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M5717
|
492 ng*h/mL
Geometric Coefficient of Variation 53.7
|
1250 ng*h/mL
Geometric Coefficient of Variation 50.0
|
2630 ng*h/mL
Geometric Coefficient of Variation 32.6
|
9290 ng*h/mL
Geometric Coefficient of Variation 25.5
|
15800 ng*h/mL
Geometric Coefficient of Variation 40.9
|
27900 ng*h/mL
Geometric Coefficient of Variation 29.7
|
37000 ng*h/mL
Geometric Coefficient of Variation 28.6
|
51300 ng*h/mL
Geometric Coefficient of Variation 33.0
|
42200 ng*h/mL
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, and 144 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The area under the plasma concentration-time curve from time zero to 144 hours after dosing was reported. It is calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to Time 144 Hours After Drug Administration (AUC0-144h) of M5717
|
475 ng*h/mL
Geometric Coefficient of Variation 44.0
|
949 ng*h/mL
Geometric Coefficient of Variation 30.3
|
1940 ng*h/mL
Geometric Coefficient of Variation 28.9
|
5830 ng*h/mL
Geometric Coefficient of Variation 29.6
|
9510 ng*h/mL
Geometric Coefficient of Variation 22.4
|
18400 ng*h/mL
Geometric Coefficient of Variation 28.8
|
24200 ng*h/mL
Geometric Coefficient of Variation 24.0
|
32200 ng*h/mL
Geometric Coefficient of Variation 24.8
|
27200 ng*h/mL
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
AUCextra% was calculated as area under the curve from time tlast extrapolated to infinity given as percentage of AUC 0-infinity. Here, tlast is the last sampling time at which the concentration is at or above the lower limit of quantification.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Extrapolated Area Under the Plasma Concentration Curve From Time of Last Quantifiable Sample to Infinity (AUCextra%) of M5717
|
45.2 percentage of AUC0-inf
Geometric Coefficient of Variation 40.5
|
26.2 percentage of AUC0-inf
Geometric Coefficient of Variation 24.3
|
24.0 percentage of AUC0-inf
Geometric Coefficient of Variation 25.8
|
6.98 percentage of AUC0-inf
Geometric Coefficient of Variation 47.1
|
5.89 percentage of AUC0-inf
Geometric Coefficient of Variation 106.5
|
2.36 percentage of AUC0-inf
Geometric Coefficient of Variation 33.2
|
2.09 percentage of AUC0-inf
Geometric Coefficient of Variation 41.9
|
2.12 percentage of AUC0-inf
Geometric Coefficient of Variation 88.7
|
1.78 percentage of AUC0-inf
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for M5717, whereas AUC0-infinity is area under the plasma concentration-time curve from time zero (dosing time) extrapolated to infinity of unchanged drug calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-infinity calculated by Clastpred/lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log linear regression line for lambda z determination at which the measured plasma concentration is at or above lower limit of quantification.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Apparent Total Clearance (CL/f) of M5717
|
39.9 Liter per hour
Geometric Coefficient of Variation 23.9
|
46.5 Liter per hour
Geometric Coefficient of Variation 44.3
|
45.5 Liter per hour
Geometric Coefficient of Variation 28.1
|
31.7 Liter per hour
Geometric Coefficient of Variation 24.9
|
27.4 Liter per hour
Geometric Coefficient of Variation 29.7
|
27.9 Liter per hour
Geometric Coefficient of Variation 29.8
|
26.3 Liter per hour
Geometric Coefficient of Variation 28.2
|
27.1 Liter per hour
Geometric Coefficient of Variation 32.4
|
38.8 Liter per hour
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz/f = Dose/(AUC0-infinity multiply by Lambda z) following single dose.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Apparent Volume of Distribution During Terminal Phase (VZ/f) of M5717
|
7640 Liters
Geometric Coefficient of Variation 45.6
|
8890 Liters
Geometric Coefficient of Variation 18.3
|
9510 Liters
Geometric Coefficient of Variation 32.9
|
7100 Liters
Geometric Coefficient of Variation 24.3
|
7160 Liters
Geometric Coefficient of Variation 24.1
|
6770 Liters
Geometric Coefficient of Variation 38.7
|
6830 Liters
Geometric Coefficient of Variation 22.5
|
7060 Liters
Geometric Coefficient of Variation 24.8
|
7870 Liters
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from the determination of the terminal first order (elimination) rate constant (lambda z). AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. Clastpred was the last predicted quantifiable concentration. Dose normalized was calculated using actual dose, using the formula AUC0-inf/Dose.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Dose Normalized AUC0-inf [AUC(0-inf/Dose)] of M5717
|
25.1 ng*h/mL/mg
Geometric Coefficient of Variation 23.9
|
21.5 ng*h/mL/mg
Geometric Coefficient of Variation 44.3
|
22.0 ng*h/mL/mg
Geometric Coefficient of Variation 28.1
|
31.5 ng*h/mL/mg
Geometric Coefficient of Variation 24.9
|
36.5 ng*h/mL/mg
Geometric Coefficient of Variation 29.7
|
35.9 ng*h/mL/mg
Geometric Coefficient of Variation 29.8
|
38.0 ng*h/mL/mg
Geometric Coefficient of Variation 28.2
|
36.9 ng*h/mL/mg
Geometric Coefficient of Variation 32.4
|
25.8 ng*h/mL/mg
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, and 144 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The area under the plasma concentration-time curve from time zero to 144 hours after dosing was reported. It is calculated using the mixed log-linear trapezoidal rule (linear up, log down). Dose normalized was calculated using actual dose, using the formula AUC0-144h/Dose.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Dose Normalized AUC0-144h [AUC(0-144hour/Dose)] of M5717
|
11.9 ng*h/mL/mg
Geometric Coefficient of Variation 44.0
|
11.9 ng*h/mL/mg
Geometric Coefficient of Variation 30.3
|
12.2 ng*h/mL/mg
Geometric Coefficient of Variation 28.9
|
18.3 ng*h/mL/mg
Geometric Coefficient of Variation 29.6
|
19.9 ng*h/mL/mg
Geometric Coefficient of Variation 22.4
|
23.1 ng*h/mL/mg
Geometric Coefficient of Variation 28.8
|
24.3 ng*h/mL/mg
Geometric Coefficient of Variation 24.0
|
22.5 ng*h/mL/mg
Geometric Coefficient of Variation 24.8
|
16.3 ng*h/mL/mg
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log-linear trapezoidal rule (linear up, log down). Dose normalized was calculated using actual dose, using the formula AUC0-t/Dose.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Dose Normalized AUC0-t [AUC( 0-t/Dose)] of M5717
|
12.4 ng*h/mL/mg
Geometric Coefficient of Variation 53.7
|
15.7 ng*h/mL/mg
Geometric Coefficient of Variation 50.0
|
16.5 ng*h/mL/mg
Geometric Coefficient of Variation 32.6
|
29.1 ng*h/mL/mg
Geometric Coefficient of Variation 25.5
|
33.1 ng*h/mL/mg
Geometric Coefficient of Variation 40.9
|
35.0 ng*h/mL/mg
Geometric Coefficient of Variation 29.7
|
37.1 ng*h/mL/mg
Geometric Coefficient of Variation 28.6
|
35.9 ng*h/mL/mg
Geometric Coefficient of Variation 33.0
|
25.3 ng*h/mL/mg
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Cmax was obtained directly from the concentration versus time curve. Dose normalized was calculated using actual dose, using the formula Cmax/Dose.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M5717
|
0.189 ng/mL/mg
Geometric Coefficient of Variation 54.3
|
0.187 ng/mL/mg
Geometric Coefficient of Variation 19.7
|
0.224 ng/mL/mg
Geometric Coefficient of Variation 41.3
|
0.459 ng/mL/mg
Geometric Coefficient of Variation 37.9
|
0.559 ng/mL/mg
Geometric Coefficient of Variation 25.4
|
0.805 ng/mL/mg
Geometric Coefficient of Variation 53.2
|
0.992 ng/mL/mg
Geometric Coefficient of Variation 40.3
|
0.815 ng/mL/mg
Geometric Coefficient of Variation 22.7
|
0.743 ng/mL/mg
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Minimal inhibitory concentration (MIC), defined as the concentration at which the relative rate of change in parasitemia is equal to zero.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Time Above or Equal to the Predicted M5717 Minimum Inhibitory Concentration (MIC) of 3 ng/mL (t =>3 ng/mL)
|
84.97 Hours
Interval 28.43 to 163.58
|
190.36 Hours
Interval 142.93 to 387.46
|
318.49 Hours
Interval 266.44 to 439.41
|
551.05 Hours
Interval 450.93 to 648.8
|
765.01 Hours
Interval 240.48 to 999.95
|
868.99 Hours
Interval 542.58 to 944.79
|
832.05 Hours
Interval 700.96 to 1031.76
|
1031.17 Hours
Interval 647.04 to 1080.71
|
867.02 Hours
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48, 72, 96, 120, 144, 192, 240, 384, 504, 768 and 1032 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PK, and provide at least one (measurable) post-dose concentration.
Minimal parasiticidal concentration represents the lowest drug concentration value above which parasites decline at a maximal rate.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 Participants
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 Participants
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 Participants
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 Participants
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 Participants
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=1 Participants
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Time Above or Equal to the Predicted M5717 Minimum Parasiticidal Concentration (MPC) of 10 ng/mL (t=>10 ng/mL)
|
0.00 Hours
Interval 0.0 to 2.03
|
12.43 Hours
Interval 1.4 to 69.8
|
88.02 Hours
Interval 46.18 to 159.2
|
272.00 Hours
Interval 227.29 to 343.13
|
436.47 Hours
Interval 240.32 to 561.56
|
506.34 Hours
Interval 312.1 to 548.62
|
531.75 Hours
Interval 441.06 to 718.23
|
708.93 Hours
Interval 437.26 to 1030.05
|
495.96 Hours
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to Day 22Population: Pharmacodynamic (PD) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PD and provided at least one (measurable) post-dose PD data. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure.
The parasite clearance time (PCT), defined as the time at which malaria parasite levels decline below detectable levels in blood after treatment, estimated as the time at which the linear portion of the optimal log parasitemia-versus-time relationship intersects the LLOQ concentration line.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=7 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Parasite Clearance Time
|
35.8 Hours
Interval 31.3 to 40.3
|
54.4 Hours
Interval 47.2 to 61.6
|
55.7 Hours
Interval 52.9 to 58.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to Day 22Population: Pharmacodynamic (PD) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PD and provided at least one (measurable) post-dose PD data. Here 'Number of Participants Analyzed' =number of participants evaluable for this outcome measure.
The parasite clearance half-life (PCt1/2), defined as the time needed for parasitemia to be reduced by half during the log-linear phase of parasite clearance, as derived using the slope of the optimal fit of the log-linear relationship of parasitemia decay. It was observed that the decline of parasitemia had a biphasic profile, with the first phase, followed by a second phase (the main clearance phase).
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=7 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Parasite Clearance Half-life (PCT 1/2)
First Phase
|
231.06 Hours
Interval 40.93 to
The NA value shown in the upper bound is a stand-in for infinity.
|
60.42 Hours
Interval 38.63 to 138.6
|
24.66 Hours
Interval 20.35 to 31.27
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Parasite Clearance Half-life (PCT 1/2)
Second Phase
|
3.52 Hours
Interval 3.12 to 4.03
|
3.89 Hours
Interval 3.27 to 4.81
|
5.47 Hours
Interval 4.78 to 6.41
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 22Population: Pharmacodynamic (PD) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PD and provided at least one (measurable) post-dose PD data.
Lag phase is defined as an initial period after dosing that precedes a steady exponential decline in the parasite count. Lag phase is categorized in lag of 4 hours, lag of 6 hours, lag of 12 hours and lag of 24 hours.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Number of Participants With Lag Phase
Lag of 4 hours
|
0 Participants
|
6 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Number of Participants With Lag Phase
Lag of 6 hours
|
3 Participants
|
0 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Number of Participants With Lag Phase
Lag of 12 hours
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Number of Participants With Lag Phase
Lag of 24 hours
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 22Population: Pharmacodynamic (PD) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PD and provided at least one (measurable) post-dose PD data.
Recrudescence is as defined as greater than and equal to 5000 blood stage parasites/milliliter (mL) and a 2-fold parasitemia increase within 48 hours, or re-occurrence of malaria symptoms with a malaria clinical score \> 6. The malaria clinical score consists of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale with minimum score is 0 (no symptoms) and the maximum score is 42 (maximum symptoms).
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Number of Participants With Recrudescence
|
3 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1, 2, 3, 4, 5, 6, 7, 9, 11, 13, 15 and 22Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 for Part C). Here, Number Analyzed signified those participants who were evaluable for the specified category at given time points.
The malaria clinical score consists of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension. Total scores are reported here. The minimum score is 0 (no symptoms) and the maximum score is 42 (maximum symptoms).
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Malarial Clinical Score
Day 1
|
0 Units on a Scale
Standard Deviation 0.4
|
0 Units on a Scale
Standard Deviation 0.0
|
1 Units on a Scale
Standard Deviation 0.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 2
|
0 Units on a Scale
Standard Deviation 0.4
|
1 Units on a Scale
Standard Deviation 0.9
|
0 Units on a Scale
Standard Deviation 0.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 3
|
1 Units on a Scale
Standard Deviation 0.8
|
0 Units on a Scale
Standard Deviation 0.5
|
0 Units on a Scale
Standard Deviation 0.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 4
|
0 Units on a Scale
Standard Deviation 0.4
|
1 Units on a Scale
Standard Deviation 0.9
|
0 Units on a Scale
Standard Deviation 0.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 5
|
0 Units on a Scale
Standard Deviation 0.4
|
0 Units on a Scale
Standard Deviation 0.4
|
0 Units on a Scale
Standard Deviation 0.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 6
|
0 Units on a Scale
Standard Deviation 0.8
|
2 Units on a Scale
Standard Deviation 0.7
|
0 Units on a Scale
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 7
|
1 Units on a Scale
Standard Deviation 0.5
|
0 Units on a Scale
Standard Deviation 0.5
|
0 Units on a Scale
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 9
|
0 Units on a Scale
Standard Deviation 0.0
|
0 Units on a Scale
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 11
|
0 Units on a Scale
Standard Deviation 0.0
|
0 Units on a Scale
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 13
|
—
|
0 Units on a Scale
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 15
|
0 Units on a Scale
Standard Deviation 0.4
|
0 Units on a Scale
Standard Deviation 0.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Malarial Clinical Score
Day 22
|
0 Units on a Scale
Standard Deviation 0.0
|
0 Units on a Scale
Standard Deviation 0.0
|
0 Units on a Scale
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to Day 22Population: Pharmacodynamic (PD) analysis set included all participants who received M5717, had no clinically important protocol deviations or important events affecting PD and provided at least one (measurable) post-dose PD data.
MIC is defined as the minimum concentration of a drug at which parasite counts continue to decrease and is equivalent to equating the rate in the change of parasite to 0. Parasiticidal concentration required for 90% killing (MPC90) is defined as the concentration at which the parasite clearance effect is at 90% of the maximum. The estimated MIC and MPC were derived from the final pharmacodynamics (PD) model and pharmacokinetic (PK)/PD relationship.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration at 90% (MPC90)
MIC
|
7.59 ng/mL
Interval 2.84 to 20.6
|
7.59 ng/mL
Interval 2.84 to 20.6
|
7.59 ng/mL
Interval 2.84 to 20.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration at 90% (MPC90)
MPC90
|
9.21 ng/mL
Interval 3.45 to 25.0
|
9.21 ng/mL
Interval 3.45 to 25.0
|
9.21 ng/mL
Interval 3.45 to 25.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Day 44Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 for Part C).
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily had a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Treatment
TEAEs
|
6 Participants
|
8 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Treatment
Serious TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part C: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Treatment
TEAE leading to Discontinuation
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Day 44Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 for Part C).
Laboratory assessments included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical significance was decided by the investigator.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Assessments
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Day 44Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 for Part C).
The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. Number of participants with clinically significant change from baseline in ECG were reported. Clinical significance was decided by the investigator.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Number of Participants With Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) Findings
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Day 44Population: Safety Analysis Set included all participants who received investigational medicinal product (M5717 for Part C).
Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. Number of participants with clinically significant change from baseline in vital signs were reported. Clinical significance was decided by the investigator.
Outcome measures
| Measure |
Part A: Placebo (Pooled)
n=6 Participants
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=8 Participants
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=8 Participants
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Part C: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Part A: Placebo (Pooled)
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Part A: Cohort 1 SAD: M5717 50 mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Part A: Cohort 2 SAD: M5717 100 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Part A: Cohort 3 SAD: M5717 200 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part A: Cohort 4 SAD: M5717 400 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part A: Cohort 5 SAD: M5717 600 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part A: Cohort 6 SAD: M5717 1000 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part A: Cohort 7 SAD: M5717 1250 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Part A: Cohort 8 SAD: M5717 1800 mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Part A: Cohort 9 SAD: M5717 2100 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part C: M5717 150 mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Part C: M5717 400 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Part C: M5717 800 mg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part A: Placebo (Pooled)
n=17 participants at risk
Participants from each cohort of Part A received single oral dose of placebo matched with M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose.
|
Part A: Cohort 1 SAD: M5717 50 mg
n=6 participants at risk
Participants received single ascending dose (SAD) of 50 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 2 SAD: M5717 100 mg
n=6 participants at risk
Participants received SAD of 100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 3 SAD: M5717 200 mg
n=6 participants at risk
Participants received SAD of 200 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 4 SAD: M5717 400 mg
n=6 participants at risk
Participants received SAD of 400 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 5 SAD: M5717 600 mg
n=6 participants at risk
Participants received SAD of 600 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 6 SAD: M5717 1000 mg
n=6 participants at risk
Participants received SAD of 1000 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 7 SAD: M5717 1250 mg
n=6 participants at risk
Participants in SAD received an oral dose of 1250 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 8 SAD: M5717 1800 mg
n=6 participants at risk
Participants in SAD received an oral dose of 1800 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part A: Cohort 9 SAD: M5717 2100 mg
n=1 participants at risk
Participants in SAD received an oral dose of 2100 mg M5717 on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 150 mg
n=6 participants at risk
Participants received single oral dose of 150 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 400 mg
n=8 participants at risk
Participants received single oral dose of 400 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
Part C: M5717 800 mg
n=8 participants at risk
Participants received single oral dose of 800 mg M5717 (eight days after the administration of intravenous malaria inoculum) on Day 1 after 8 hours fasting-period followed by a 4-hour post-dose fast.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
75.0%
6/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
37.5%
3/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Eye disorders
Vision blurred
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
50.0%
3/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
100.0%
1/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
25.0%
2/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Epigastric discomfort
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Gingival pain
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
100.0%
1/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Nausea
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
General disorders
Catheter site bruise
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
General disorders
Catheter site induration
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
General disorders
Catheter site pain
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
General disorders
Chills
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
General disorders
Fatigue
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
General disorders
Vessel puncture site bruise
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Infections and infestations
Abscess limb
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Infections and infestations
Folliculitis
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Infections and infestations
Hordeolum
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Infections and infestations
Upper respiratory tract infection
|
11.8%
2/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Injury, poisoning and procedural complications
Contusion
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Injury, poisoning and procedural complications
Sunburn
|
17.6%
3/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
37.5%
3/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Injury, poisoning and procedural complications
Vascular access site bruising
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Investigations
Blood corticotrophin decreased
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Investigations
Lymph node palpable
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Nervous system disorders
Dizziness
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
50.0%
3/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Nervous system disorders
Headache
|
17.6%
3/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
50.0%
3/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
66.7%
4/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
50.0%
3/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
62.5%
5/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
50.0%
4/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Nervous system disorders
Mental impairment
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Nervous system disorders
Paraesthesia
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Nervous system disorders
Sensory disturbance
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
50.0%
3/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
25.0%
2/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
5.9%
1/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Vascular disorders
Flushing
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Vascular disorders
Hot flush
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Blood and lymphatic system disorders
Eosinophilia
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
25.0%
2/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
62.5%
5/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
25.0%
2/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
25.0%
2/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Gastrointestinal disorders
Abdominal tenderness
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
100.0%
1/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
25.0%
2/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
General disorders
Malaise
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Nervous system disorders
Lethargy
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
General disorders
Pyrexia
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
33.3%
2/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
16.7%
1/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
66.7%
4/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
25.0%
2/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/17 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/1 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/6 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
12.5%
1/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
0.00%
0/8 • For Part A: Baseline up to Day 55. For Part C: Baseline up to Day 44.
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place