Trial Outcomes & Findings for Study Investigating the Safety, Tolerability, PK and Food Effect of BEN8744. (NCT NCT06118385)
NCT ID: NCT06118385
Last Updated: 2025-05-07
Results Overview
The investigator/designee scored the participant's level of alertness on a scale of 0 (absence of response to stimulus) to 5 (readily responsive to the subject's name in a normal tone) in each of 4 components (responsiveness, speech, facial expression, eyes). The composite score corresponds to the lowest score for any component. The sum is the sum of the 4 component scores, ranging from 9 to 20. Positive change in composite score or sum is a better outcome; negative change is a worse outcome.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
76 participants
Primary outcome timeframe
From Baseline (predose on Day 1) through 72 hours postdose
Results posted on
2025-05-07
Participant Flow
Participant milestones
| Measure |
Part A Placebo
Single dose of placebo capsule(s) matched to active dose
|
Part A Dose 1
Single 2 mg dose of BEN8744
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose of BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
Part B Dose 1
Single 30 mg dose of BEN8744 administered after 10-hour fast and after high-fat breakfast
|
Part B Dose 2
Single 50 mg dose of BEN8744 administered after 10-hour fast and after high-fat breakfast
|
Part C Placebo
Placebo capsules matched to active dose twice-daily for 14 days
|
Part C Dose 1
30 mg BEN8744 twice-daily for 14 days
|
Part C Dose 2
50 mg BEN8744 twice-daily for 14 days
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
4
|
6
|
6
|
|
Overall Study
COMPLETED
|
12
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
4
|
4
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Part A Placebo
Single dose of placebo capsule(s) matched to active dose
|
Part A Dose 1
Single 2 mg dose of BEN8744
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose of BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
Part B Dose 1
Single 30 mg dose of BEN8744 administered after 10-hour fast and after high-fat breakfast
|
Part B Dose 2
Single 50 mg dose of BEN8744 administered after 10-hour fast and after high-fat breakfast
|
Part C Placebo
Placebo capsules matched to active dose twice-daily for 14 days
|
Part C Dose 1
30 mg BEN8744 twice-daily for 14 days
|
Part C Dose 2
50 mg BEN8744 twice-daily for 14 days
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Out-of-range blood tests
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Study Investigating the Safety, Tolerability, PK and Food Effect of BEN8744.
Baseline characteristics by cohort
| Measure |
Part A Placebo
n=12 Participants
Single dose of placebo capsule(s) matched to active dose
|
Part A Dose 1
n=6 Participants
Single 2 mg dose of BEN8744
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose of BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
n=6 Participants
Single 120 mg dose of BEN8744
|
Part B (Both Groups)
n=12 Participants
Dose 1: Single 30 mg dose of BEN8744 administered after 10-hour fast and after high-fat breakfast; Dose 2: Single 50 mg dose of BEN8744 administered after 10-hour fast and after high-fat breakfast
|
Part C Placebo
n=4 Participants
Placebo capsules matched to active dose twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Total
n=76 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
37.3 years
STANDARD_DEVIATION 14.83 • n=93 Participants
|
39.0 years
STANDARD_DEVIATION 8.44 • n=4 Participants
|
27.8 years
STANDARD_DEVIATION 4.49 • n=27 Participants
|
32.7 years
STANDARD_DEVIATION 12.77 • n=483 Participants
|
34.3 years
STANDARD_DEVIATION 4.13 • n=36 Participants
|
43.0 years
STANDARD_DEVIATION 13.08 • n=10 Participants
|
31.0 years
STANDARD_DEVIATION 9.08 • n=115 Participants
|
41.9 years
STANDARD_DEVIATION 14.30 • n=40 Participants
|
38.5 years
STANDARD_DEVIATION 9.47 • n=8 Participants
|
38.3 years
STANDARD_DEVIATION 12.75 • n=62 Participants
|
31.5 years
STANDARD_DEVIATION 5.89 • n=95 Participants
|
35.9 years
STANDARD_DEVIATION 4.82 • n=129 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
4 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=62 Participants
|
2 Participants
n=95 Participants
|
22 Participants
n=129 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
5 Participants
n=36 Participants
|
5 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
8 Participants
n=40 Participants
|
4 Participants
n=8 Participants
|
5 Participants
n=62 Participants
|
4 Participants
n=95 Participants
|
54 Participants
n=129 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
4 Participants
n=129 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
5 Participants
n=36 Participants
|
6 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
12 Participants
n=40 Participants
|
3 Participants
n=8 Participants
|
6 Participants
n=62 Participants
|
6 Participants
n=95 Participants
|
72 Participants
n=129 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
4 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=62 Participants
|
1 Participants
n=95 Participants
|
12 Participants
n=129 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
1 Participants
n=95 Participants
|
14 Participants
n=129 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
3 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
6 Participants
n=40 Participants
|
2 Participants
n=8 Participants
|
5 Participants
n=62 Participants
|
3 Participants
n=95 Participants
|
42 Participants
n=129 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=40 Participants
|
1 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
1 Participants
n=95 Participants
|
5 Participants
n=129 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
3 Participants
n=129 Participants
|
|
Region of Enrollment
United Kingdom
|
12 participants
n=93 Participants
|
6 participants
n=4 Participants
|
6 participants
n=27 Participants
|
6 participants
n=483 Participants
|
6 participants
n=36 Participants
|
6 participants
n=10 Participants
|
6 participants
n=115 Participants
|
12 participants
n=40 Participants
|
4 participants
n=8 Participants
|
6 participants
n=62 Participants
|
6 participants
n=95 Participants
|
76 participants
n=129 Participants
|
PRIMARY outcome
Timeframe: From Baseline (predose on Day 1) through 72 hours postdoseThe investigator/designee scored the participant's level of alertness on a scale of 0 (absence of response to stimulus) to 5 (readily responsive to the subject's name in a normal tone) in each of 4 components (responsiveness, speech, facial expression, eyes). The composite score corresponds to the lowest score for any component. The sum is the sum of the 4 component scores, ranging from 9 to 20. Positive change in composite score or sum is a better outcome; negative change is a worse outcome.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=12 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
n=6 Participants
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (0.25 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (0.5 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (1 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (2 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (4 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (6 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (8 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (24 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (48 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (72 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (0.25 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Composite score (3 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (0.5 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (1 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (2 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (3 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (4 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (6 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (8 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (24 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (48 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
Sum (72 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
PRIMARY outcome
Timeframe: From Baseline (predose on Day 1) through 72 hours postdoseThe participant graded level of alertness by placing a mark on a linear scale from 0 (very alert) to 100 (very drowsy). Negative change is a better outcome; positive change is a worse outcome.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=12 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
n=6 Participants
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (0.25 hour)
|
-3.0 mm on a 100-mm line (change)
Standard Deviation 7.29
|
1.8 mm on a 100-mm line (change)
Standard Deviation 4.59
|
0.5 mm on a 100-mm line (change)
Standard Deviation 4.32
|
3.7 mm on a 100-mm line (change)
Standard Deviation 7.37
|
-1.2 mm on a 100-mm line (change)
Standard Deviation 1.94
|
-5.8 mm on a 100-mm line (change)
Standard Deviation 7.73
|
-5.5 mm on a 100-mm line (change)
Standard Deviation 19.42
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (0.5 hour)
|
0.5 mm on a 100-mm line (change)
Standard Deviation 12.76
|
0.3 mm on a 100-mm line (change)
Standard Deviation 5.80
|
3.8 mm on a 100-mm line (change)
Standard Deviation 17.29
|
2.7 mm on a 100-mm line (change)
Standard Deviation 13.98
|
1.0 mm on a 100-mm line (change)
Standard Deviation 3.79
|
-2.8 mm on a 100-mm line (change)
Standard Deviation 9.52
|
-3.3 mm on a 100-mm line (change)
Standard Deviation 35.30
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (1 hour)
|
-8.2 mm on a 100-mm line (change)
Standard Deviation 13.06
|
1.9 mm on a 100-mm line (change)
Standard Deviation 4.64
|
14.8 mm on a 100-mm line (change)
Standard Deviation 30.64
|
6.3 mm on a 100-mm line (change)
Standard Deviation 12.86
|
1.8 mm on a 100-mm line (change)
Standard Deviation 7.14
|
-2.0 mm on a 100-mm line (change)
Standard Deviation 7.38
|
-2.0 mm on a 100-mm line (change)
Standard Deviation 37.83
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (2 hours)
|
-9.3 mm on a 100-mm line (change)
Standard Deviation 12.69
|
6.7 mm on a 100-mm line (change)
Standard Deviation 12.03
|
6.2 mm on a 100-mm line (change)
Standard Deviation 8.33
|
2.0 mm on a 100-mm line (change)
Standard Deviation 12.93
|
1.3 mm on a 100-mm line (change)
Standard Deviation 5.85
|
0.7 mm on a 100-mm line (change)
Standard Deviation 8.52
|
4.0 mm on a 100-mm line (change)
Standard Deviation 38.76
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (3 hours)
|
-10.3 mm on a 100-mm line (change)
Standard Deviation 22.00
|
3.5 mm on a 100-mm line (change)
Standard Deviation 9.11
|
3.7 mm on a 100-mm line (change)
Standard Deviation 6.59
|
4.3 mm on a 100-mm line (change)
Standard Deviation 17.20
|
-1.2 mm on a 100-mm line (change)
Standard Deviation 6.62
|
3.3 mm on a 100-mm line (change)
Standard Deviation 7.66
|
-4.7 mm on a 100-mm line (change)
Standard Deviation 30.69
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (4 hours)
|
-11.2 mm on a 100-mm line (change)
Standard Deviation 14.33
|
1.2 mm on a 100-mm line (change)
Standard Deviation 11.44
|
3.7 mm on a 100-mm line (change)
Standard Deviation 8.52
|
1.2 mm on a 100-mm line (change)
Standard Deviation 14.66
|
-2.3 mm on a 100-mm line (change)
Standard Deviation 4.50
|
6.8 mm on a 100-mm line (change)
Standard Deviation 10.46
|
5.0 mm on a 100-mm line (change)
Standard Deviation 28.87
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (6 hours)
|
-14.3 mm on a 100-mm line (change)
Standard Deviation 15.91
|
1.8 mm on a 100-mm line (change)
Standard Deviation 7.00
|
3.5 mm on a 100-mm line (change)
Standard Deviation 7.23
|
4.3 mm on a 100-mm line (change)
Standard Deviation 27.98
|
7.0 mm on a 100-mm line (change)
Standard Deviation 19.83
|
1.5 mm on a 100-mm line (change)
Standard Deviation 17.03
|
-2.2 mm on a 100-mm line (change)
Standard Deviation 34.74
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (8 hours)
|
3.7 mm on a 100-mm line (change)
Standard Deviation 30.06
|
2.1 mm on a 100-mm line (change)
Standard Deviation 9.58
|
0.0 mm on a 100-mm line (change)
Standard Deviation 2.37
|
7.3 mm on a 100-mm line (change)
Standard Deviation 24.36
|
-2.2 mm on a 100-mm line (change)
Standard Deviation 7.68
|
8.0 mm on a 100-mm line (change)
Standard Deviation 17.20
|
-7.8 mm on a 100-mm line (change)
Standard Deviation 28.53
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (24 hours)
|
-5.7 mm on a 100-mm line (change)
Standard Deviation 10.95
|
-0.4 mm on a 100-mm line (change)
Standard Deviation 10.32
|
-1.0 mm on a 100-mm line (change)
Standard Deviation 6.54
|
-3.3 mm on a 100-mm line (change)
Standard Deviation 9.83
|
0.5 mm on a 100-mm line (change)
Standard Deviation 8.48
|
-2.7 mm on a 100-mm line (change)
Standard Deviation 10.86
|
-11.5 mm on a 100-mm line (change)
Standard Deviation 31.86
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (48 hours)
|
-10.3 mm on a 100-mm line (change)
Standard Deviation 11.67
|
-2.5 mm on a 100-mm line (change)
Standard Deviation 9.99
|
-2.5 mm on a 100-mm line (change)
Standard Deviation 5.47
|
-4.0 mm on a 100-mm line (change)
Standard Deviation 10.30
|
-2.0 mm on a 100-mm line (change)
Standard Deviation 8.69
|
-6.5 mm on a 100-mm line (change)
Standard Deviation 13.43
|
-2.8 mm on a 100-mm line (change)
Standard Deviation 32.46
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
Score (72 hours)
|
-15.7 mm on a 100-mm line (change)
Standard Deviation 16.17
|
-4.1 mm on a 100-mm line (change)
Standard Deviation 10.30
|
-2.3 mm on a 100-mm line (change)
Standard Deviation 5.54
|
-4.5 mm on a 100-mm line (change)
Standard Deviation 9.59
|
-3.7 mm on a 100-mm line (change)
Standard Deviation 7.00
|
-9.3 mm on a 100-mm line (change)
Standard Deviation 15.21
|
-6.5 mm on a 100-mm line (change)
Standard Deviation 33.41
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Cmax (PK Part B)
|
88.8 ng/mL
Geometric Coefficient of Variation 33.2
|
76.7 ng/mL
Geometric Coefficient of Variation 41.4
|
265 ng/mL
Geometric Coefficient of Variation 50.0
|
173 ng/mL
Geometric Coefficient of Variation 56.3
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Tmax (PK Part B)
|
2.02 Hours
Interval 1.0 to 3.0
|
1.08 Hours
Interval 1.0 to 3.0
|
1.00 Hours
Interval 0.5 to 2.03
|
3.00 Hours
Interval 2.02 to 4.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose in each of the 2 treatment periods (fasted and fed)Area under the plasma concentration-time curve from time 0 to 24 hours postdose. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUC24 (PK Part B)
|
332 ng.hour/mL
Geometric Coefficient of Variation 25.2
|
227 ng.hour/mL
Geometric Coefficient of Variation 25.0
|
721 ng.hour/mL
Geometric Coefficient of Variation 47.9
|
666 ng.hour/mL
Geometric Coefficient of Variation 54.3
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Area under the plasma concentration-time curve from time 0 to 72 hours postdose. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUC72 (PK Part B)
|
335 ng.hour/mL
Geometric Coefficient of Variation 26.0
|
229 ng.hour/mL
Geometric Coefficient of Variation 24.3
|
723 ng.hour/mL
Geometric Coefficient of Variation 48.4
|
669 ng.hour/mL
Geometric Coefficient of Variation 54.9
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Area under the plasma concentration-time curve from time zero to time of last measurable concentration. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUClast (PK Part B)
|
332 ng.hour/mL
Geometric Coefficient of Variation 25.7
|
226 ng.hour/mL
Geometric Coefficient of Variation 24.8
|
721 ng.hour/mL
Geometric Coefficient of Variation 48.5
|
667 ng.hour/mL
Geometric Coefficient of Variation 54.9
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Area under the plasma concentration-time curve from time 0 to infinity. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUCinf (PK Part B)
|
335 ng.hour/mL
Geometric Coefficient of Variation 26.1
|
228 ng.hour/mL
Geometric Coefficient of Variation 24.4
|
723 ng.hour/mL
Geometric Coefficient of Variation 48.5
|
669 ng.hour/mL
Geometric Coefficient of Variation 55.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Terminal half-life. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
t1⁄2 (PK Part B)
|
4.83 Hours
Standard Deviation 3.67
|
4.12 Hours
Standard Deviation 2.26
|
4.23 Hours
Standard Deviation 5.14
|
3.83 Hours
Standard Deviation 4.69
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Terminal Rate Constant (PK Part B)
|
0.217 /hour
Standard Deviation 0.132
|
0.210 /hour
Standard Deviation 0.0956
|
0.300 /hour
Standard Deviation 0.144
|
0.340 /hour
Standard Deviation 0.173
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
CL/F (PK Part B)
|
92.0 L/hour
Standard Deviation 22.7
|
135 L/hour
Standard Deviation 33.7
|
75.1 L/hour
Standard Deviation 34.3
|
82.3 L/hour
Standard Deviation 36.4
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
VZ/F (PK Part B)
|
550 L
Standard Deviation 268
|
846 L
Standard Deviation 582
|
327 L
Standard Deviation 218
|
310 L
Standard Deviation 186
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose in each of the 2 treatment periods (fasted and fed)Percentage of AUCinf extrapolated from time of last measurable concentration to infinity. Calculated from plasma concentrations collected at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=5 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
%AUCextrap (PK Part B)
|
0.638 Percentage of AUC
Geometric Coefficient of Variation 73.1
|
0.991 Percentage of AUC
Geometric Coefficient of Variation 70.2
|
0.156 Percentage of AUC
Geometric Coefficient of Variation 129.4
|
0.198 Percentage of AUC
Geometric Coefficient of Variation 78.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From Baseline (predose on Day 1) through 48 hours postdoseThe investigator/designee scored the participant's level of alertness on a scale of 0 (absence of response to stimulus) to 5 (readily responsive to the subject's name in a normal tone) in each of 4 components (responsiveness, speech, facial expression, eyes). The composite score corresponds to the lowest score for any component. The sum is the sum of the 4 component scores, ranging from 9 to 20. Positive change in composite score or sum is a better outcome; negative change is a worse outcome.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=4 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (48 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (8 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (0.25 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (0.5 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (1 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (2 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (3 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (4 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (6 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (8 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (24 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Composite score (48 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (0.25 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (0.5 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (1 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (2 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (24 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (3 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (4 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
Sum (6 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From Baseline (predose on Day 1) through 48 hours postdoseThe participant graded level of alertness by placing a mark on a linear scale from 0 (very alert) to 100 (very drowsy). Negative change is a better outcome; positive change is a worse outcome.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=4 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (3 hours)
|
11.0 mm on a 100-mm line (change)
Standard Deviation 30.33
|
18.0 mm on a 100-mm line (change)
Standard Deviation 32.14
|
7.3 mm on a 100-mm line (change)
Standard Deviation 16.82
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (4 hours)
|
8.2 mm on a 100-mm line (change)
Standard Deviation 21.03
|
15.3 mm on a 100-mm line (change)
Standard Deviation 27.04
|
1.5 mm on a 100-mm line (change)
Standard Deviation 9.27
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (0.25 hour)
|
2.2 mm on a 100-mm line (change)
Standard Deviation 13.33
|
1.0 mm on a 100-mm line (change)
Standard Deviation 3.56
|
-0.3 mm on a 100-mm line (change)
Standard Deviation 5.96
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (0.5 hour)
|
2.7 mm on a 100-mm line (change)
Standard Deviation 14.02
|
2.5 mm on a 100-mm line (change)
Standard Deviation 9.29
|
1.8 mm on a 100-mm line (change)
Standard Deviation 6.11
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (1 hour)
|
15.8 mm on a 100-mm line (change)
Standard Deviation 31.91
|
27.3 mm on a 100-mm line (change)
Standard Deviation 24.73
|
4.0 mm on a 100-mm line (change)
Standard Deviation 15.66
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (2 hours)
|
13.0 mm on a 100-mm line (change)
Standard Deviation 26.48
|
18.8 mm on a 100-mm line (change)
Standard Deviation 24.43
|
7.2 mm on a 100-mm line (change)
Standard Deviation 17.85
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (6 hours)
|
5.3 mm on a 100-mm line (change)
Standard Deviation 18.68
|
7.3 mm on a 100-mm line (change)
Standard Deviation 22.53
|
6.3 mm on a 100-mm line (change)
Standard Deviation 16.43
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (8 hours)
|
7.3 mm on a 100-mm line (change)
Standard Deviation 18.55
|
1.0 mm on a 100-mm line (change)
Standard Deviation 9.63
|
-2.5 mm on a 100-mm line (change)
Standard Deviation 8.07
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (24 hours)
|
12.2 mm on a 100-mm line (change)
Standard Deviation 18.36
|
25.8 mm on a 100-mm line (change)
Standard Deviation 25.91
|
7.2 mm on a 100-mm line (change)
Standard Deviation 24.68
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
Score (48 hours)
|
3.2 mm on a 100-mm line (change)
Standard Deviation 11.96
|
8.0 mm on a 100-mm line (change)
Standard Deviation 6.98
|
2.0 mm on a 100-mm line (change)
Standard Deviation 11.37
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Completed during screening and on Days 17 and 24The C-SSRS is a questionnaire completed by the Investigator, who asks yes/no questions of the participant It I used to categorise risk levels based on the responses.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=4 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)
No or low risk - Day 24
|
6 Participants
|
4 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
|
Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)
No or low risk - Day 17
|
6 Participants
|
4 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Cmax (PK Part A)
|
4.20 ng/mL
Geometric Coefficient of Variation 77.2
|
1.10 ng/mL
Geometric Coefficient of Variation 73.9
|
43.7 ng/mL
Geometric Coefficient of Variation 40.8
|
297 ng/mL
Geometric Coefficient of Variation 74.1
|
548 ng/mL
Geometric Coefficient of Variation 33.1
|
695 ng/mL
Geometric Coefficient of Variation 54.8
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Tmax (PK Part A)
|
1.50 Hours
Interval 0.517 to 3.0
|
2.00 Hours
Interval 1.98 to 2.05
|
2.03 Hours
Interval 1.03 to 3.03
|
1.00 Hours
Interval 1.0 to 2.0
|
2.00 Hours
Interval 1.0 to 3.0
|
1.00 Hours
Interval 1.0 to 3.0
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the plasma concentration-time curve from time 0 to 24 hours postdose. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUC24 (PK Part A)
|
13.8 ng.hour/mL
Geometric Coefficient of Variation 54.1
|
NA ng.hour/mL
Geometric Coefficient of Variation NA
The concentration was below the limit of quantitation at some timepoints, resulting in insufficient data to calculate this endpoint.
|
154 ng.hour/mL
Geometric Coefficient of Variation 42.2
|
901 ng.hour/mL
Geometric Coefficient of Variation 62.9
|
1781 ng.hour/mL
Geometric Coefficient of Variation 40.6
|
1949 ng.hour/mL
Geometric Coefficient of Variation 45.1
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the plasma concentration-time curve from time 0 to 72 hours postdose. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUC72 (PK Part A)
|
13.9 ng.hour/mL
Geometric Coefficient of Variation 54.2
|
NA ng.hour/mL
Geometric Coefficient of Variation NA
The concentration was below the limit of quantitation at some timepoints, resulting in insufficient data to calculate this endpoint.
|
155 ng.hour/mL
Geometric Coefficient of Variation 42.4
|
904 ng.hour/mL
Geometric Coefficient of Variation 63.3
|
1788 ng.hour/mL
Geometric Coefficient of Variation 41.1
|
1959 ng.hour/mL
Geometric Coefficient of Variation 44.8
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUClast (PK Part A)
|
12.9 ng.hour/mL
Geometric Coefficient of Variation 59.8
|
2.56 ng.hour/mL
Geometric Coefficient of Variation 76.1
|
153 ng.hour/mL
Geometric Coefficient of Variation 42.8
|
902 ng.hour/mL
Geometric Coefficient of Variation 63.3
|
1786 ng.hour/mL
Geometric Coefficient of Variation 41.1
|
1955 ng.hour/mL
Geometric Coefficient of Variation 45.0
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the plasma concentration-time curve from time 0 to infinity. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUCinf (PK Part A)
|
13.8 ng.hour/mL
Geometric Coefficient of Variation 53.9
|
NA ng.hour/mL
Geometric Coefficient of Variation NA
The concentration was below the limit of quantitation at some timepoints, resulting in insufficient data to calculate this endpoint.
|
155 ng.hour/mL
Geometric Coefficient of Variation 42.4
|
904 ng.hour/mL
Geometric Coefficient of Variation 63.3
|
1788 ng.hour/mL
Geometric Coefficient of Variation 41.2
|
1959 ng.hour/mL
Geometric Coefficient of Variation 44.8
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Percentage of AUCinf extrapolated from time of last measurable concentration to infinity. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
%AUCextrap (PK Part A)
|
4.95 Percentage of AUC
Geometric Coefficient of Variation 76.2
|
6.62 Percentage of AUC
Geometric Coefficient of Variation NA
The concentration was below the limit of quantitation at some timepoints, resulting in insufficient data to calculate AUC for all but one participant, so no coefficient of variation can be calculated.
|
0.910 Percentage of AUC
Geometric Coefficient of Variation 69.8
|
0.202 Percentage of AUC
Geometric Coefficient of Variation 126.7
|
0.0796 Percentage of AUC
Geometric Coefficient of Variation 125.8
|
0.108 Percentage of AUC
Geometric Coefficient of Variation 236.0
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Terminal half-life. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
t1⁄2 (PK Part A)
|
1.89 Hours
Standard Deviation 0.709
|
NA Hours
Standard Deviation NA
The concentration was below the limit of quantitation at some timepoints, resulting in insufficient data to calculate this endpoint.
|
3.50 Hours
Standard Deviation 0.983
|
4.51 Hours
Standard Deviation 3.41
|
5.57 Hours
Standard Deviation 5.95
|
7.12 Hours
Standard Deviation 4.48
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Terminal Rate Constant (PK Part A)
|
0.419 /Hour
Standard Deviation 0.172
|
NA /Hour
Standard Deviation NA
The concentration was below the limit of quantitation at some timepoints, resulting in insufficient data to calculate this endpoint.
|
0.214 /Hour
Standard Deviation 0.0702
|
0.216 /Hour
Standard Deviation 0.107
|
0.221 /Hour
Standard Deviation 0.127
|
0.143 /Hour
Standard Deviation 0.100
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
CL/F (PK Part A)
|
489 L/hour
Standard Deviation 287
|
NA L/hour
Standard Deviation NA
The concentration was below the limit of quantitation at some timepoints, resulting in insufficient data to calculate this endpoint.
|
139 L/hour
Standard Deviation 65.5
|
75.0 L/hour
Standard Deviation 36.2
|
59.4 L/hour
Standard Deviation 21.3
|
66.4 L/hour
Standard Deviation 31.2
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdosePopulation: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=6 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 Participants
Single 60 mg dose BEN8744
|
Part A Dose 5
n=6 Participants
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
VZ/F (PK Part A)
|
1268 L
Standard Deviation 747
|
NA L
Standard Deviation NA
The concentration was below the limit of quantitation at some timepoints, resulting in insufficient data to calculate this endpoint.
|
666 L
Standard Deviation 241
|
384 L
Standard Deviation 147
|
374 L
Standard Deviation 227
|
720 L
Standard Deviation 549
|
—
|
SECONDARY outcome
Timeframe: From Baseline (predose on Day 1) through 72 hours postdoseThe investigator/designee scored the participant's level of alertness on a scale of 0 (absence of response to stimulus) to 5 (readily responsive to the subject's name in a normal tone) in each of 4 components (responsiveness, speech, facial expression, eyes). The composite score corresponds to the lowest score for any component. The sum is the sum of the 4 component scores, ranging from 9 to 20. Positive change in composite score or sum is a better outcome; negative change is a worse outcome.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (6 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (0.25 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (0.5 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (4 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (8 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (48 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (72 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (0.5 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (1 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (6 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (8 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (24 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (48 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (72 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (24 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (0.25 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (1 hour)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (2 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Composite score (3 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (2 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (3 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
|
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
Sum (4 hours)
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
0 score on a scale (change)
Standard Deviation 0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline (predose on Day 1) through 72 hours postdoseThe participant graded level of alertness by placing a mark on a linear scale from 0 (very alert) to 100 (very drowsy). Negative change is a better outcome; positive change is a worse outcome.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
n=5 Participants
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=5 Participants
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (1 hour)
|
6.2 mm on a 100-mm line (change)
Standard Deviation 12.09
|
1.0 mm on a 100-mm line (change)
Standard Deviation 4.10
|
16.4 mm on a 100-mm line (change)
Standard Deviation 36.22
|
2.8 mm on a 100-mm line (change)
Standard Deviation 12.56
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (2 hours)
|
6.7 mm on a 100-mm line (change)
Standard Deviation 14.08
|
6.0 mm on a 100-mm line (change)
Standard Deviation 10.94
|
14.4 mm on a 100-mm line (change)
Standard Deviation 30.07
|
9.6 mm on a 100-mm line (change)
Standard Deviation 25.44
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (6 hours)
|
7.0 mm on a 100-mm line (change)
Standard Deviation 19.29
|
15.7 mm on a 100-mm line (change)
Standard Deviation 17.51
|
10.0 mm on a 100-mm line (change)
Standard Deviation 32.61
|
1.8 mm on a 100-mm line (change)
Standard Deviation 7.98
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (8 hours)
|
9.8 mm on a 100-mm line (change)
Standard Deviation 15.84
|
7.5 mm on a 100-mm line (change)
Standard Deviation 14.87
|
1.2 mm on a 100-mm line (change)
Standard Deviation 5.31
|
0.2 mm on a 100-mm line (change)
Standard Deviation 3.42
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (24 hours)
|
7.7 mm on a 100-mm line (change)
Standard Deviation 11.89
|
8.5 mm on a 100-mm line (change)
Standard Deviation 12.18
|
-6.0 mm on a 100-mm line (change)
Standard Deviation 11.58
|
6.8 mm on a 100-mm line (change)
Standard Deviation 13.14
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (72 hours)
|
2.3 mm on a 100-mm line (change)
Standard Deviation 9.46
|
-1.8 mm on a 100-mm line (change)
Standard Deviation 8.33
|
-6.0 mm on a 100-mm line (change)
Standard Deviation 10.22
|
-3.0 mm on a 100-mm line (change)
Standard Deviation 3.32
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (0.25 hour)
|
1.7 mm on a 100-mm line (change)
Standard Deviation 6.80
|
-0.7 mm on a 100-mm line (change)
Standard Deviation 2.73
|
-3.0 mm on a 100-mm line (change)
Standard Deviation 4.30
|
-1.6 mm on a 100-mm line (change)
Standard Deviation 1.34
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (0.5 hour)
|
8.0 mm on a 100-mm line (change)
Standard Deviation 12.79
|
2.3 mm on a 100-mm line (change)
Standard Deviation 3.78
|
3.0 mm on a 100-mm line (change)
Standard Deviation 14.61
|
-0.2 mm on a 100-mm line (change)
Standard Deviation 2.86
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (3 hours)
|
5.0 mm on a 100-mm line (change)
Standard Deviation 17.81
|
4.7 mm on a 100-mm line (change)
Standard Deviation 6.92
|
-2.2 mm on a 100-mm line (change)
Standard Deviation 14.58
|
-2.0 mm on a 100-mm line (change)
Standard Deviation 3.39
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (4 hours)
|
8.3 mm on a 100-mm line (change)
Standard Deviation 10.89
|
8.3 mm on a 100-mm line (change)
Standard Deviation 16.54
|
2.2 mm on a 100-mm line (change)
Standard Deviation 18.53
|
8.6 mm on a 100-mm line (change)
Standard Deviation 16.06
|
—
|
—
|
—
|
|
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
Score (48 hours)
|
3.5 mm on a 100-mm line (change)
Standard Deviation 9.27
|
9.5 mm on a 100-mm line (change)
Standard Deviation 10.84
|
-5.0 mm on a 100-mm line (change)
Standard Deviation 14.21
|
3.6 mm on a 100-mm line (change)
Standard Deviation 13.28
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Maximum (peak) plasma concentration. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Cmax (PK Part C)
AM Day 14
|
241 ng/mL
Geometric Coefficient of Variation 49.9
|
85.4 ng/mL
Geometric Coefficient of Variation 50.0
|
—
|
—
|
—
|
—
|
—
|
|
Cmax (PK Part C)
AM Day 1
|
198 ng/mL
Geometric Coefficient of Variation 47.8
|
77.9 ng/mL
Geometric Coefficient of Variation 56.0
|
—
|
—
|
—
|
—
|
—
|
|
Cmax (PK Part C)
PM Day 1
|
138 ng/mL
Geometric Coefficient of Variation 47.8
|
49.5 ng/mL
Geometric Coefficient of Variation 89.2
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Tmax (PK Part C)
AM Day 1
|
1.51 Hours
Interval 1.0 to 2.0
|
2.00 Hours
Interval 0.5 to 2.0
|
—
|
—
|
—
|
—
|
—
|
|
Tmax (PK Part C)
PM Day 1
|
3.00 Hours
Interval 2.0 to 4.0
|
3.03 Hours
Interval 1.0 to 7.95
|
—
|
—
|
—
|
—
|
—
|
|
Tmax (PK Part C)
AM Day 14
|
2.00 Hours
Interval 1.0 to 3.0
|
2.08 Hours
Interval 1.0 to 3.02
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Trough plasma concentration. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Ctrough (PK Part C)
Day 1, 12 hours
|
1.65 ng/mL
Interval 0.865 to 3.16
|
0.684 ng/mL
Interval 0.385 to 1.22
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 2
|
3.57 ng/mL
Interval 1.7 to 7.53
|
1.81 ng/mL
Interval 0.875 to 3.75
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 3
|
4.68 ng/mL
Interval 1.78 to 12.3
|
2.97 ng/mL
Interval 1.22 to 7.23
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 5
|
6.47 ng/mL
Interval 2.61 to 16.1
|
2.39 ng/mL
Interval 0.978 to 5.83
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 7
|
7.09 ng/mL
Interval 3.07 to 16.4
|
2.73 ng/mL
Interval 1.43 to 5.21
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 9
|
6.97 ng/mL
Interval 3.63 to 13.4
|
2.87 ng/mL
Interval 0.907 to 9.09
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 11
|
4.27 ng/mL
Interval 2.03 to 9.01
|
1.95 ng/mL
Interval 0.647 to 5.9
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 13
|
4.72 ng/mL
Interval 2.18 to 10.2
|
3.41 ng/mL
Interval 1.46 to 7.98
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 14
|
6.28 ng/mL
Interval 3.34 to 11.8
|
3.24 ng/mL
Interval 1.35 to 7.78
|
—
|
—
|
—
|
—
|
—
|
|
Ctrough (PK Part C)
Day 14, 12 hours
|
4.93 ng/mL
Interval 2.26 to 10.8
|
2.19 ng/mL
Interval 1.14 to 4.21
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the concentration-time curve across a dosing interval. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUCtau (PK Part C)
AM Day 14
|
792 ng.hour/mL
Geometric Coefficient of Variation 59.0
|
254 ng.hour/mL
Geometric Coefficient of Variation 68.9
|
—
|
—
|
—
|
—
|
—
|
|
AUCtau (PK Part C)
AM Day 1
|
521 ng.hour/mL
Geometric Coefficient of Variation 59.2
|
210 ng.hour/mL
Geometric Coefficient of Variation 48.3
|
—
|
—
|
—
|
—
|
—
|
|
AUCtau (PK Part C)
PM Day 1
|
540 ng.hour/mL
Geometric Coefficient of Variation 53.9
|
231 ng.hour/mL
Geometric Coefficient of Variation 92.5
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the concentration-time curve from time 0 to the last measurable timepoint. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUClast (PK Part C)
Day1
|
1034 ng.hour/mL
Geometric Coefficient of Variation 47.5
|
410 ng.hour/mL
Geometric Coefficient of Variation 59.0
|
—
|
—
|
—
|
—
|
—
|
|
AUClast (PK Part C)
Day 14
|
831 ng.hour/mL
Geometric Coefficient of Variation 59.3
|
270 ng.hour/mL
Geometric Coefficient of Variation 67.8
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the plasma concentration-time curve from time 0 to 72 hours postdose. Calculated from plasma concentrations measured at the time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUC72 (PK Part C)
|
837 ng.hour/mL
Geometric Coefficient of Variation 58.9
|
273 ng.hour/mL
Geometric Coefficient of Variation 66.9
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Terminal half-life. Maximum (peak) plasma concentration. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
t1⁄2 (PK Part C)
Day 1
|
1.63 Hours
Standard Deviation 0.177
|
1.68 Hours
Standard Deviation 0.317
|
—
|
—
|
—
|
—
|
—
|
|
t1⁄2 (PK Part C)
Day 14
|
9.87 Hours
Standard Deviation 7.35
|
5.89 Hours
Standard Deviation 2.82
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the plasma concentration-time curve from time 0 to infinity. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
AUCinf (PK Part C)
Day 1
|
1149 ng.hour/mL
Geometric Coefficient of Variation 52.8
|
449 ng.hour/mL
Geometric Coefficient of Variation 72.3
|
—
|
—
|
—
|
—
|
—
|
|
AUCinf (PK Part C)
Day 14
|
839 ng.hour/mL
Geometric Coefficient of Variation 58.9
|
273 ng.hour/mL
Geometric Coefficient of Variation 66.9
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Percentage of AUCinf extrapolated from time of last measurable concentration to infinity. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
%AUCextrap (PK Part C)
Day 1
|
0.832 Percentage of AUC
Geometric Coefficient of Variation 93.4
|
1.36 Percentage of AUC
Geometric Coefficient of Variation 219.5
|
—
|
—
|
—
|
—
|
—
|
|
%AUCextrap (PK Part C)
Day 14
|
0.921 Percentage of AUC
Geometric Coefficient of Variation 63.6
|
1.14 Percentage of AUC
Geometric Coefficient of Variation 85.3
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Terminal Rate Constant (PK Part C)
Day 1
|
0.428 /Hour
Standard Deviation 0.0428
|
0.424 /Hour
Standard Deviation 0.0848
|
—
|
—
|
—
|
—
|
—
|
|
Terminal Rate Constant (PK Part C)
Day 14
|
0.123 /Hour
Standard Deviation 0.0955
|
0.169 /Hour
Standard Deviation 0.148
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Systemic clearance relative to bioavailability at steady state (Day 14). Calculated from plasma concentrations measured at the time points below.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
CLSS/F (PK Part C)
|
70.2 L/hour
Standard Deviation 31.5
|
139 L/hour
Standard Deviation 87.1
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Apparent volume of distribution relative to absolute bioavailability (Day 14). Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
VZ/F (PK Part C)
|
977 L
Standard Deviation 874
|
1221 L
Standard Deviation 823
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the concentration-time curve over the dosing interval on Day 14/area under the concentration-time curve over the dosing interval on Day 1 in AM. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Rac(AUCtau) (PK Part C)
|
1.65 ratio
Standard Deviation 0.840
|
1.33 ratio
Standard Deviation 0.679
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Maximum observed plasma concentration on Day 14/maximum observed plasma concentration on Day 1 in AM. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
Rac(Cmax) (PK Part C)
|
1.29 ratio
Standard Deviation 0.559
|
1.22 ratio
Standard Deviation 0.673
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.
Area under the concentration-time curve across a dosing interval on Day 14/area under the concentration-time curve from time 0 to infinity. Calculated from plasma concentrations measured before the morning dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20 and 24 hours after the morning dose on Day 1; before the morning dose on Days 3, 5, 7, 9, 11, and 13; and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 20, 24, 36, 48, and 72 hours after the morning dose on Day 14.
Outcome measures
| Measure |
Part C Dose 2
n=6 Participants
50 mg BEN8744 twice-daily for 14 days
|
Part C Dose 1
n=6 Participants
30 mg BEN8744 twice-daily for 14 days
|
Part A Dose 2
Single 6 mg dose of BEN8744
|
Part A Dose 3
Single 20 mg dose of BEN8744
|
Part A Dose 4
Single 60 mg dose BEN8744
|
Part A Dose 5
Single 100 mg dose of BEN8744
|
Part A Dose 6
Single 120 mg dose of BEN8744
|
|---|---|---|---|---|---|---|---|
|
SR(AUC) (PK Part C)
|
0.733 ratio
Standard Deviation 0.158
|
0.556 ratio
Standard Deviation 0.275
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Part A Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Part A Dose 1
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part A Dose 2
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part A Dose 3
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part A Dose 4
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part A Dose 5
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part A Dose 6
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part B Dose 1 Fasted
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part B Dose 1 Fed
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part B Dose 2 Fasted
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Part B Dose 2 Fed
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part C Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part C Dose 1
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part C Dose 2
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part A Placebo
n=12 participants at risk
Single dose of placebo capsule(s) matched to active dose
|
Part A Dose 1
n=6 participants at risk
Single 2 mg dose of BEN8744
|
Part A Dose 2
n=6 participants at risk
Single 6 mg dose of BEN8744
|
Part A Dose 3
n=6 participants at risk
Single 20 mg dose of BEN8744
|
Part A Dose 4
n=6 participants at risk
Single 60 mg dose of BEN8744
|
Part A Dose 5
n=6 participants at risk
Single 100 mg dose of BEN8744
|
Part A Dose 6
n=6 participants at risk
Single 120 mg dose of BEN8744
|
Part B Dose 1 Fasted
n=6 participants at risk
Single 30 mg dose of BEN8744 after 10-hour fast
|
Part B Dose 1 Fed
n=6 participants at risk
Single 30 mg dose of BEN8744 after a high-fat breakfast
|
Part B Dose 2 Fasted
n=5 participants at risk
Single 50 mg dose of BEN8744 after 10-hour fast
|
Part B Dose 2 Fed
n=5 participants at risk
Single 50 mg dose of BEN8744 after a high-fat breakfast
|
Part C Placebo
n=4 participants at risk
Placebo capsules matched to active dose twice-daily for 14 days
|
Part C Dose 1
n=6 participants at risk
30 mg BEN8744 twice-daily for 14 days
|
Part C Dose 2
n=6 participants at risk
50 mg BEN8744 twice-daily for 14 days
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
25.0%
1/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Nervous system disorders
Headache
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
General disorders
Fatigue
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Investigations
Hepatic enzymes increased
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
20.0%
1/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
20.0%
1/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Nervous system disorders
Somnolence
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
25.0%
1/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Skin and subcutaneous tissue disorders
Eczema asteatotic
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
25.0%
1/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/12 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
16.7%
1/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/5 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/4 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
0.00%
0/6 • From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER