Study Investigating the Safety, Tolerability, PK and Food Effect of BEN8744.

A Randomised, Double-blind, Placebo-controlled, Phase 1 First-in-human Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Food Effect of Single- and Multiple-ascending Doses of BEN8744 in Healthy Subjects.

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06118385

Enrollment

Registered

2023-11-07

Start date

2023-08-30

Completion date

2024-03-18

Last updated

2025-05-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteer Study

Brief summary

BEN8744 is an experimental new medicine for treating inflammatory bowel diseases such as Ulcerative Colitis. The study will test single and repeated oral doses of BEN8744 or placebo. BEN8744 is a first in human study, so will start with a small dose and the dose will be increased as the study progresses. The goal is to find out its side effects and blood levels when taken by mouth and whether food affects the blood levels. This is a 3-part study (Parts A, B and C) in up to 108 healthy people, aged 18-65. Part A, will include up to 64 participants, single doses of BEN8744 or placebo. They'll take about 2 weeks to finish the study, stay on the ward for 4 nights and 5 days in a row and make 2 outpatient visits. Part B, will include up to 12 participants, single doses of BEN8744 with and without food. They'll take up to 3 weeks to finish the study, stay on the ward for 4 nights and 5 days in a row on 2 occasions, and make 2 outpatient visits. Part C will include up to 32 participants repeat doses of the BEN8744 or placebo for 14 days. They'll take about 4 weeks to complete the study, stay on the ward for 17 nights and 18 days in a row and make 2 outpatient visits.

Detailed description

This first time in human, study will investigate the safety, tolerability, pharmacokinetics (PK) of BEN8744 after single and multiple ascending oral doses in healthy subjects, in both the fed and fasted state. The results of this study will be used to select doses for subsequent studies in patients. This is an exploratory study in healthy volunteers, with no anticipated therapeutic benefit to the participants; involvement of patients, service users or members of the public in the design of the trial is not appropriate. Primary objectives Part A: To assess the safety and tolerability of single ascending oral doses of BEN8744 in healthy subjects Part B: To characterise the effect of food on the pharmacokinetic profile of at least 1 dose of BEN8744 Part C: To assess the safety and tolerability of multiple ascending oral doses of BEN8744 in healthy subjects Secondary objectives Part A: To assess the PK profile of BEN8744 after single oral doses in healthy subjects Part B: To assess the safety and tolerability of a single dose of BEN8744 following high-fat food intake relative to fasting conditions in healthy subjects Part C: To assess the PK profile of BEN8744 after repeated oral doses in healthy subjects Exploratory objective Part B (and optional in Part C): To measure BEN8744 in urine and determine renal clearance in healthy subjects. Exploratory characterisation of BEN8744 and its metabolites in plasma, urine, and faeces. For part A * Up to 64 subjects, 5 cohorts + 3 optional, 6 active, 2 placebo. * Subjects will receive a single dose of BEN8744 or placebo, as capsules, after an overnight fast of at least 10 h. * At each dose level, 6 subjects will receive BEN8744 and 2 will receive matching placebo in an overall ratio of 3:1. * The starting dose for Group 1 is 2 mg BEN8744 or placebo. It is intended that subsequent cohorts will receive higher doses. The planned doses are: A1- 2mg A2- 6mg A3- 20mg A4- 60mg A5- 100mg A6 (optional) - 120mg For Part B * Up to 12 subjects, 1 cohorts + 1 optional, 2 sessions fasted/fed. * Each subject in Part B will have 2 study sessions (Sessions 1 and 2), in which they will receive a single dose of BEN8744, by mouth. * Each subject will receive BEN8744 after an overnight fast of at least 10 h in one session, and after an FDA high-fat breakfast (1,013 kcal, 59.2 g fat \[of which 28.1 g saturated fat) in the other session; the order will be randomised 1:1. * A subject's doses will be separated by a washout of at least 7 days (or 5 half-lives as determined in Part A, whichever is longer). * Subjects dosed on the same day may be dosed at intervals of at least 10 min. For Part C: * Up 32 subjects, 3 cohorts + 1 optional, 6 active, 2 placebo. * Each subject will receive daily doses of BEN8744 or placebo, by mouth, for 14 days. * Doses will be taken once or twice daily in the fasted state, unless emerging data indicate they should be taken in the fed state. * Part C will not start until at least 3 dose levels have been completed in Part A and may also be conducted in parallel with Part B.

Interventions

DRUGBEN8744

Formulated powder in capsule for oral administration. Supplied as filled Size 0 Swedish Orange capsule. Doses: 2mg, 10mg and 40mg.

DRUGMatching Placebo

Formulated powder in capsule for oral administration. Supplied as filled Size 0 Swedish Orange capsule. Doses: 2mg, 10mg and 40mg.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Intervention model description

The trial will be in 3 parts: Part A will investigate single ascending oral doses of BEN8744; Part B is a 2-way crossover assessment of the effect of food on the PK of BEN8744; and Part C will investigate multiple ascending oral doses of BEN8744

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

1. Male or female healthy volunteer in good health 2. Aged 18-65 years 3. Body mass index 18.0-30.9 and weight ≥ 50 kg

Exclusion criteria

1\. Woman who is pregnant or lactating, or pre-menopausal woman who is sexually active and not using a reliable method of contraception

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)	From Baseline (predose on Day 1) through 72 hours postdose	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.
Change From Baseline in Visual Analogue Scale (VAS) (Part A)	From Baseline (predose on Day 1) through 72 hours postdose	The 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.
Cmax (PK Part B)	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.
Tmax (PK Part B)	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.
AUC24 (PK Part B)	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.
AUC72 (PK Part B)	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.
AUClast (PK Part B)	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.
AUCinf (PK Part B)	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.
t1⁄2 (PK Part B)	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.
Terminal Rate Constant (PK Part B)	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.
CL/F (PK Part B)	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.
VZ/F (PK Part B)	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.
%AUCextrap (PK Part B)	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.
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)	From Baseline (predose on Day 1) through 48 hours postdose	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.
Change From Baseline in Visual Analogue Scale (VAS) (Part C)	From Baseline (predose on Day 1) through 48 hours postdose	The 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.
Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)	Completed during screening and on Days 17 and 24	The 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.

Secondary

Measure	Time frame	Description
AUCtau (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
AUClast (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
AUC72 (PK Part C)	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	Area under the plasma concentration-time curve from time 0 to 72 hours postdose. Calculated from plasma concentrations measured at the time points below.
t1⁄2 (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
AUCinf (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
%AUCextrap (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
Terminal Rate Constant (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
CLSS/F (PK Part C)	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 14	Systemic clearance relative to bioavailability at steady state (Day 14). Calculated from plasma concentrations measured at the time points below.
VZ/F (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
Rac(AUCtau) (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
Rac(Cmax) (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
Cmax (PK Part A)	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	Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.
SR(AUC) (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
Tmax (PK Part A)	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	Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.
AUC24 (PK Part A)	Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours postdose	Area under the plasma concentration-time curve from time 0 to 24 hours postdose. Calculated from plasma concentrations at time points below.
AUC72 (PK Part A)	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	Area under the plasma concentration-time curve from time 0 to 72 hours postdose. Calculated from plasma concentrations at time points below.
AUClast (PK Part A)	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	Area under the plasma concentration-time curve from time 0 to time of last measurable concentration. Calculated from plasma concentrations at time points below.
AUCinf (PK Part A)	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	Area under the plasma concentration-time curve from time 0 to infinity. Calculated from plasma concentrations at time points below.
%AUCextrap (PK Part A)	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	Percentage of AUCinf extrapolated from time of last measurable concentration to infinity. Calculated from plasma concentrations at time points below.
t1⁄2 (PK Part A)	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	Terminal half-life. Calculated from plasma concentrations at time points below.
Terminal Rate Constant (PK Part A)	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	Calculated from plasma concentrations at time points below.
CL/F (PK Part A)	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	Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below.
VZ/F (PK Part A)	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	Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below.
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)	From Baseline (predose on Day 1) through 72 hours postdose	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.
Change From Baseline in Visual Analogue Scale (VAS) (Part B)	From Baseline (predose on Day 1) through 72 hours postdose	The 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.
Cmax (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
Tmax (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.
Ctrough (PK Part C)	Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above)	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.

Countries

United Kingdom

Participant flow

Participants by arm

Arm	Count
Part A Placebo Single dose of placebo capsule(s) matched to active dose	12
Part A Dose 1 Single 2 mg dose of BEN8744	6
Part A Dose 2 Single 6 mg dose of BEN8744	6
Part A Dose 3 Single 20 mg dose of BEN8744	6
Part A Dose 4 Single 60 mg dose of BEN8744	6
Part A Dose 5 Single 100 mg dose of BEN8744	6
Part A Dose 6 Single 120 mg dose of BEN8744	6
Part B (Both Groups) 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	12
Part C Placebo Placebo capsules matched to active dose twice-daily for 14 days	4
Part C Dose 1 30 mg BEN8744 twice-daily for 14 days	6
Part C Dose 2 50 mg BEN8744 twice-daily for 14 days	6
Total	76

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011
Overall Study	Out-of-range blood tests	0	0	0	0	0	0	0	0	1	0	0	0
Overall Study	Protocol Violation	0	0	0	0	0	0	0	0	1	0	0	0

Baseline characteristics

Characteristic	Part A Placebo	Total	Part C Dose 2	Part C Dose 1	Part C Placebo	Part B (Both Groups)	Part A Dose 6	Part A Dose 5	Part A Dose 4	Part A Dose 3	Part A Dose 2	Part A Dose 1
Age, Continuous	37.3 years STANDARD_DEVIATION 14.83	35.9 years STANDARD_DEVIATION 4.82	31.5 years STANDARD_DEVIATION 5.89	38.3 years STANDARD_DEVIATION 12.75	38.5 years STANDARD_DEVIATION 9.47	41.9 years STANDARD_DEVIATION 14.3	31.0 years STANDARD_DEVIATION 9.08	43.0 years STANDARD_DEVIATION 13.08	34.3 years STANDARD_DEVIATION 4.13	32.7 years STANDARD_DEVIATION 12.77	27.8 years STANDARD_DEVIATION 4.49	39.0 years STANDARD_DEVIATION 8.44
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	4 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants	72 Participants	6 Participants	6 Participants	3 Participants	12 Participants	6 Participants	6 Participants	5 Participants	6 Participants	5 Participants	6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	12 Participants	1 Participants	1 Participants	0 Participants	4 Participants	2 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	14 Participants	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants	2 Participants	0 Participants	2 Participants	3 Participants	1 Participants
Race (NIH/OMB) More than one race	1 Participants	5 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	3 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	7 Participants	42 Participants	3 Participants	5 Participants	2 Participants	6 Participants	2 Participants	3 Participants	4 Participants	4 Participants	2 Participants	4 Participants
Region of Enrollment United Kingdom	12 participants	76 participants	6 participants	6 participants	4 participants	12 participants	6 participants	6 participants	6 participants	6 participants	6 participants	6 participants
Sex: Female, Male Female	6 Participants	22 Participants	2 Participants	1 Participants	0 Participants	4 Participants	2 Participants	1 Participants	1 Participants	2 Participants	0 Participants	3 Participants
Sex: Female, Male Male	6 Participants	54 Participants	4 Participants	5 Participants	4 Participants	8 Participants	4 Participants	5 Participants	5 Participants	4 Participants	6 Participants	3 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 5	0 / 5	0 / 4	0 / 6	0 / 6
other Total, other adverse events	0 / 12	1 / 6	1 / 6	4 / 6	2 / 6	2 / 6	1 / 6	1 / 6	1 / 6	0 / 5	2 / 5	3 / 4	1 / 6	2 / 6
serious Total, serious adverse events	0 / 12	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 5	0 / 5	0 / 4	0 / 6	0 / 6

Outcome results

Primary

AUC24 (PK Part B)

Area under the plasma concentration-time curve from time 0 to 24 hours postdose. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUC24 (PK Part B)	227 ng.hour/mL	Geometric Coefficient of Variation 25
Part A Dose 1	AUC24 (PK Part B)	332 ng.hour/mL	Geometric Coefficient of Variation 25.2
Part A Dose 2	AUC24 (PK Part B)	721 ng.hour/mL	Geometric Coefficient of Variation 47.9
Part A Dose 3	AUC24 (PK Part B)	666 ng.hour/mL	Geometric Coefficient of Variation 54.3

Primary

AUC72 (PK Part B)

Area under the plasma concentration-time curve from time 0 to 72 hours postdose. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUC72 (PK Part B)	229 ng.hour/mL	Geometric Coefficient of Variation 24.3
Part A Dose 1	AUC72 (PK Part B)	335 ng.hour/mL	Geometric Coefficient of Variation 26
Part A Dose 2	AUC72 (PK Part B)	723 ng.hour/mL	Geometric Coefficient of Variation 48.4
Part A Dose 3	AUC72 (PK Part B)	669 ng.hour/mL	Geometric Coefficient of Variation 54.9

Primary

%AUCextrap (PK Part B)

Percentage of AUCinf extrapolated from time of last measurable concentration to infinity. Calculated from plasma concentrations collected at time points below.

Time frame: 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)

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	%AUCextrap (PK Part B)	0.991 Percentage of AUC	Geometric Coefficient of Variation 70.2
Part A Dose 1	%AUCextrap (PK Part B)	0.638 Percentage of AUC	Geometric Coefficient of Variation 73.1
Part A Dose 2	%AUCextrap (PK Part B)	0.156 Percentage of AUC	Geometric Coefficient of Variation 129.4
Part A Dose 3	%AUCextrap (PK Part B)	0.198 Percentage of AUC	Geometric Coefficient of Variation 78

Primary

AUCinf (PK Part B)

Area under the plasma concentration-time curve from time 0 to infinity. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUCinf (PK Part B)	228 ng.hour/mL	Geometric Coefficient of Variation 24.4
Part A Dose 1	AUCinf (PK Part B)	335 ng.hour/mL	Geometric Coefficient of Variation 26.1
Part A Dose 2	AUCinf (PK Part B)	723 ng.hour/mL	Geometric Coefficient of Variation 48.5
Part A Dose 3	AUCinf (PK Part B)	669 ng.hour/mL	Geometric Coefficient of Variation 55

Primary

AUClast (PK Part B)

Area under the plasma concentration-time curve from time zero to time of last measurable concentration. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUClast (PK Part B)	226 ng.hour/mL	Geometric Coefficient of Variation 24.8
Part A Dose 1	AUClast (PK Part B)	332 ng.hour/mL	Geometric Coefficient of Variation 25.7
Part A Dose 2	AUClast (PK Part B)	721 ng.hour/mL	Geometric Coefficient of Variation 48.5
Part A Dose 3	AUClast (PK Part B)	667 ng.hour/mL	Geometric Coefficient of Variation 54.9

Primary

Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)

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.

Time frame: From Baseline (predose on Day 1) through 72 hours postdose

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 4	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 5	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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
Part A Dose 6	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

Primary

Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)

Time frame: From Baseline (predose on Day 1) through 48 hours postdose

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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

Primary

Change From Baseline in Visual Analogue Scale (VAS) (Part A)

The 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.

Time frame: From Baseline (predose on Day 1) through 72 hours postdose

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (2 hours)	6.7 mm on a 100-mm line (change)	Standard Deviation 12.03
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.5 hour)	0.3 mm on a 100-mm line (change)	Standard Deviation 5.8
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (8 hours)	2.1 mm on a 100-mm line (change)	Standard Deviation 9.58
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (3 hours)	3.5 mm on a 100-mm line (change)	Standard Deviation 9.11
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.25 hour)	1.8 mm on a 100-mm line (change)	Standard Deviation 4.59
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (6 hours)	1.8 mm on a 100-mm line (change)	Standard Deviation 7
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (48 hours)	-2.5 mm on a 100-mm line (change)	Standard Deviation 9.99
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (1 hour)	1.9 mm on a 100-mm line (change)	Standard Deviation 4.64
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (4 hours)	1.2 mm on a 100-mm line (change)	Standard Deviation 11.44
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (72 hours)	-4.1 mm on a 100-mm line (change)	Standard Deviation 10.3
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (24 hours)	-0.4 mm on a 100-mm line (change)	Standard Deviation 10.32
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (6 hours)	3.5 mm on a 100-mm line (change)	Standard Deviation 7.23
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (4 hours)	3.7 mm on a 100-mm line (change)	Standard Deviation 8.52
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.25 hour)	0.5 mm on a 100-mm line (change)	Standard Deviation 4.32
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.5 hour)	3.8 mm on a 100-mm line (change)	Standard Deviation 17.29
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (48 hours)	-2.5 mm on a 100-mm line (change)	Standard Deviation 5.47
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (1 hour)	14.8 mm on a 100-mm line (change)	Standard Deviation 30.64
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (24 hours)	-1.0 mm on a 100-mm line (change)	Standard Deviation 6.54
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (2 hours)	6.2 mm on a 100-mm line (change)	Standard Deviation 8.33
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (72 hours)	-2.3 mm on a 100-mm line (change)	Standard Deviation 5.54
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (8 hours)	0.0 mm on a 100-mm line (change)	Standard Deviation 2.37
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (3 hours)	3.7 mm on a 100-mm line (change)	Standard Deviation 6.59
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (4 hours)	1.2 mm on a 100-mm line (change)	Standard Deviation 14.66
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.25 hour)	3.7 mm on a 100-mm line (change)	Standard Deviation 7.37
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.5 hour)	2.7 mm on a 100-mm line (change)	Standard Deviation 13.98
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (1 hour)	6.3 mm on a 100-mm line (change)	Standard Deviation 12.86
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (2 hours)	2.0 mm on a 100-mm line (change)	Standard Deviation 12.93
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (3 hours)	4.3 mm on a 100-mm line (change)	Standard Deviation 17.2
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (6 hours)	4.3 mm on a 100-mm line (change)	Standard Deviation 27.98
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (8 hours)	7.3 mm on a 100-mm line (change)	Standard Deviation 24.36
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (24 hours)	-3.3 mm on a 100-mm line (change)	Standard Deviation 9.83
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (48 hours)	-4.0 mm on a 100-mm line (change)	Standard Deviation 10.3
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (72 hours)	-4.5 mm on a 100-mm line (change)	Standard Deviation 9.59
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (3 hours)	-1.2 mm on a 100-mm line (change)	Standard Deviation 6.62
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.25 hour)	-1.2 mm on a 100-mm line (change)	Standard Deviation 1.94
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (6 hours)	7.0 mm on a 100-mm line (change)	Standard Deviation 19.83
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (2 hours)	1.3 mm on a 100-mm line (change)	Standard Deviation 5.85
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (8 hours)	-2.2 mm on a 100-mm line (change)	Standard Deviation 7.68
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (1 hour)	1.8 mm on a 100-mm line (change)	Standard Deviation 7.14
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (72 hours)	-3.7 mm on a 100-mm line (change)	Standard Deviation 7
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (24 hours)	0.5 mm on a 100-mm line (change)	Standard Deviation 8.48
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.5 hour)	1.0 mm on a 100-mm line (change)	Standard Deviation 3.79
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (48 hours)	-2.0 mm on a 100-mm line (change)	Standard Deviation 8.69
Part A Dose 4	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (4 hours)	-2.3 mm on a 100-mm line (change)	Standard Deviation 4.5
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (8 hours)	8.0 mm on a 100-mm line (change)	Standard Deviation 17.2
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (1 hour)	-2.0 mm on a 100-mm line (change)	Standard Deviation 7.38
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.25 hour)	-5.8 mm on a 100-mm line (change)	Standard Deviation 7.73
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (3 hours)	3.3 mm on a 100-mm line (change)	Standard Deviation 7.66
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (4 hours)	6.8 mm on a 100-mm line (change)	Standard Deviation 10.46
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (24 hours)	-2.7 mm on a 100-mm line (change)	Standard Deviation 10.86
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.5 hour)	-2.8 mm on a 100-mm line (change)	Standard Deviation 9.52
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (72 hours)	-9.3 mm on a 100-mm line (change)	Standard Deviation 15.21
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (48 hours)	-6.5 mm on a 100-mm line (change)	Standard Deviation 13.43
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (6 hours)	1.5 mm on a 100-mm line (change)	Standard Deviation 17.03
Part A Dose 5	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (2 hours)	0.7 mm on a 100-mm line (change)	Standard Deviation 8.52
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (48 hours)	-2.8 mm on a 100-mm line (change)	Standard Deviation 32.46
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (1 hour)	-2.0 mm on a 100-mm line (change)	Standard Deviation 37.83
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (3 hours)	-4.7 mm on a 100-mm line (change)	Standard Deviation 30.69
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (72 hours)	-6.5 mm on a 100-mm line (change)	Standard Deviation 33.41
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.25 hour)	-5.5 mm on a 100-mm line (change)	Standard Deviation 19.42
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (6 hours)	-2.2 mm on a 100-mm line (change)	Standard Deviation 34.74
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (2 hours)	4.0 mm on a 100-mm line (change)	Standard Deviation 38.76
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (24 hours)	-11.5 mm on a 100-mm line (change)	Standard Deviation 31.86
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (0.5 hour)	-3.3 mm on a 100-mm line (change)	Standard Deviation 35.3
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (8 hours)	-7.8 mm on a 100-mm line (change)	Standard Deviation 28.53
Part A Dose 6	Change From Baseline in Visual Analogue Scale (VAS) (Part A)	Score (4 hours)	5.0 mm on a 100-mm line (change)	Standard Deviation 28.87

Primary

Change From Baseline in Visual Analogue Scale (VAS) (Part C)

The 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.

Time frame: From Baseline (predose on Day 1) through 48 hours postdose

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (0.25 hour)	1.0 mm on a 100-mm line (change)	Standard Deviation 3.56
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (0.5 hour)	2.5 mm on a 100-mm line (change)	Standard Deviation 9.29
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (1 hour)	27.3 mm on a 100-mm line (change)	Standard Deviation 24.73
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (2 hours)	18.8 mm on a 100-mm line (change)	Standard Deviation 24.43
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (3 hours)	18.0 mm on a 100-mm line (change)	Standard Deviation 32.14
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (4 hours)	15.3 mm on a 100-mm line (change)	Standard Deviation 27.04
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (6 hours)	7.3 mm on a 100-mm line (change)	Standard Deviation 22.53
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (8 hours)	1.0 mm on a 100-mm line (change)	Standard Deviation 9.63
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (24 hours)	25.8 mm on a 100-mm line (change)	Standard Deviation 25.91
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (48 hours)	8.0 mm on a 100-mm line (change)	Standard Deviation 6.98
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (8 hours)	-2.5 mm on a 100-mm line (change)	Standard Deviation 8.07
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (2 hours)	7.2 mm on a 100-mm line (change)	Standard Deviation 17.85
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (3 hours)	7.3 mm on a 100-mm line (change)	Standard Deviation 16.82
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (4 hours)	1.5 mm on a 100-mm line (change)	Standard Deviation 9.27
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (24 hours)	7.2 mm on a 100-mm line (change)	Standard Deviation 24.68
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (6 hours)	6.3 mm on a 100-mm line (change)	Standard Deviation 16.43
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (0.25 hour)	-0.3 mm on a 100-mm line (change)	Standard Deviation 5.96
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (48 hours)	2.0 mm on a 100-mm line (change)	Standard Deviation 11.37
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (0.5 hour)	1.8 mm on a 100-mm line (change)	Standard Deviation 6.11
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part C)	Score (1 hour)	4.0 mm on a 100-mm line (change)	Standard Deviation 15.66

Primary

CL/F (PK Part B)

Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	CL/F (PK Part B)	135 L/hour	Standard Deviation 33.7
Part A Dose 1	CL/F (PK Part B)	92.0 L/hour	Standard Deviation 22.7
Part A Dose 2	CL/F (PK Part B)	75.1 L/hour	Standard Deviation 34.3
Part A Dose 3	CL/F (PK Part B)	82.3 L/hour	Standard Deviation 36.4

Primary

Cmax (PK Part B)

Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	Cmax (PK Part B)	76.7 ng/mL	Geometric Coefficient of Variation 41.4
Part A Dose 1	Cmax (PK Part B)	88.8 ng/mL	Geometric Coefficient of Variation 33.2
Part A Dose 2	Cmax (PK Part B)	265 ng/mL	Geometric Coefficient of Variation 50
Part A Dose 3	Cmax (PK Part B)	173 ng/mL	Geometric Coefficient of Variation 56.3

Primary

Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)

The 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.

Time frame: Completed during screening and on Days 17 and 24

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part A Placebo	Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)	No or low risk - Day 17	4 Participants
Part A Placebo	Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)	No or low risk - Day 24	4 Participants
Part A Dose 1	Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)	No or low risk - Day 17	6 Participants
Part A Dose 1	Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)	No or low risk - Day 24	6 Participants
Part A Dose 2	Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)	No or low risk - Day 17	6 Participants
Part A Dose 2	Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)	No or low risk - Day 24	6 Participants

Primary

t1⁄2 (PK Part B)

Terminal half-life. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	t1⁄2 (PK Part B)	4.12 Hours	Standard Deviation 2.26
Part A Dose 1	t1⁄2 (PK Part B)	4.83 Hours	Standard Deviation 3.67
Part A Dose 2	t1⁄2 (PK Part B)	4.23 Hours	Standard Deviation 5.14
Part A Dose 3	t1⁄2 (PK Part B)	3.83 Hours	Standard Deviation 4.69

Primary

Terminal Rate Constant (PK Part B)

Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	Terminal Rate Constant (PK Part B)	0.210 /hour	Standard Deviation 0.0956
Part A Dose 1	Terminal Rate Constant (PK Part B)	0.217 /hour	Standard Deviation 0.132
Part A Dose 2	Terminal Rate Constant (PK Part B)	0.300 /hour	Standard Deviation 0.144
Part A Dose 3	Terminal Rate Constant (PK Part B)	0.340 /hour	Standard Deviation 0.173

Primary

Tmax (PK Part B)

Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (MEDIAN)
Part A Placebo	Tmax (PK Part B)	1.08 Hours
Part A Dose 1	Tmax (PK Part B)	2.02 Hours
Part A Dose 2	Tmax (PK Part B)	1.00 Hours
Part A Dose 3	Tmax (PK Part B)	3.00 Hours

Primary

VZ/F (PK Part B)

Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below.

Time frame: 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)

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	VZ/F (PK Part B)	846 L	Standard Deviation 582
Part A Dose 1	VZ/F (PK Part B)	550 L	Standard Deviation 268
Part A Dose 2	VZ/F (PK Part B)	327 L	Standard Deviation 218
Part A Dose 3	VZ/F (PK Part B)	310 L	Standard Deviation 186

Secondary

AUC24 (PK Part A)

Area under the plasma concentration-time curve from time 0 to 24 hours postdose. Calculated from plasma concentrations at time points below.

Time frame: Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours postdose

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUC24 (PK Part A)	NA ng.hour/mL	—
Part A Dose 1	AUC24 (PK Part A)	13.8 ng.hour/mL	Geometric Coefficient of Variation 54.1
Part A Dose 2	AUC24 (PK Part A)	154 ng.hour/mL	Geometric Coefficient of Variation 42.2
Part A Dose 3	AUC24 (PK Part A)	901 ng.hour/mL	Geometric Coefficient of Variation 62.9
Part A Dose 4	AUC24 (PK Part A)	1781 ng.hour/mL	Geometric Coefficient of Variation 40.6
Part A Dose 5	AUC24 (PK Part A)	1949 ng.hour/mL	Geometric Coefficient of Variation 45.1

Secondary

AUC72 (PK Part A)

Area under the plasma concentration-time curve from time 0 to 72 hours postdose. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUC72 (PK Part A)	NA ng.hour/mL	—
Part A Dose 1	AUC72 (PK Part A)	13.9 ng.hour/mL	Geometric Coefficient of Variation 54.2
Part A Dose 2	AUC72 (PK Part A)	155 ng.hour/mL	Geometric Coefficient of Variation 42.4
Part A Dose 3	AUC72 (PK Part A)	904 ng.hour/mL	Geometric Coefficient of Variation 63.3
Part A Dose 4	AUC72 (PK Part A)	1788 ng.hour/mL	Geometric Coefficient of Variation 41.1
Part A Dose 5	AUC72 (PK Part A)	1959 ng.hour/mL	Geometric Coefficient of Variation 44.8

Secondary

AUC72 (PK Part C)

Area under the plasma concentration-time curve from time 0 to 72 hours postdose. Calculated from plasma concentrations measured at the time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUC72 (PK Part C)	273 ng.hour/mL	Geometric Coefficient of Variation 66.9
Part A Dose 1	AUC72 (PK Part C)	837 ng.hour/mL	Geometric Coefficient of Variation 58.9

Secondary

%AUCextrap (PK Part A)

Percentage of AUCinf extrapolated from time of last measurable concentration to infinity. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	%AUCextrap (PK Part A)	6.62 Percentage of AUC	—
Part A Dose 1	%AUCextrap (PK Part A)	4.95 Percentage of AUC	Geometric Coefficient of Variation 76.2
Part A Dose 2	%AUCextrap (PK Part A)	0.910 Percentage of AUC	Geometric Coefficient of Variation 69.8
Part A Dose 3	%AUCextrap (PK Part A)	0.202 Percentage of AUC	Geometric Coefficient of Variation 126.7
Part A Dose 4	%AUCextrap (PK Part A)	0.0796 Percentage of AUC	Geometric Coefficient of Variation 125.8
Part A Dose 5	%AUCextrap (PK Part A)	0.108 Percentage of AUC	Geometric Coefficient of Variation 236

Secondary

%AUCextrap (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	%AUCextrap (PK Part C)	Day 1	1.36 Percentage of AUC	Geometric Coefficient of Variation 219.5
Part A Placebo	%AUCextrap (PK Part C)	Day 14	1.14 Percentage of AUC	Geometric Coefficient of Variation 85.3
Part A Dose 1	%AUCextrap (PK Part C)	Day 1	0.832 Percentage of AUC	Geometric Coefficient of Variation 93.4
Part A Dose 1	%AUCextrap (PK Part C)	Day 14	0.921 Percentage of AUC	Geometric Coefficient of Variation 63.6

Secondary

AUCinf (PK Part A)

Area under the plasma concentration-time curve from time 0 to infinity. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUCinf (PK Part A)	NA ng.hour/mL	—
Part A Dose 1	AUCinf (PK Part A)	13.8 ng.hour/mL	Geometric Coefficient of Variation 53.9
Part A Dose 2	AUCinf (PK Part A)	155 ng.hour/mL	Geometric Coefficient of Variation 42.4
Part A Dose 3	AUCinf (PK Part A)	904 ng.hour/mL	Geometric Coefficient of Variation 63.3
Part A Dose 4	AUCinf (PK Part A)	1788 ng.hour/mL	Geometric Coefficient of Variation 41.2
Part A Dose 5	AUCinf (PK Part A)	1959 ng.hour/mL	Geometric Coefficient of Variation 44.8

Secondary

AUCinf (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUCinf (PK Part C)	Day 1	449 ng.hour/mL	Geometric Coefficient of Variation 72.3
Part A Placebo	AUCinf (PK Part C)	Day 14	273 ng.hour/mL	Geometric Coefficient of Variation 66.9
Part A Dose 1	AUCinf (PK Part C)	Day 1	1149 ng.hour/mL	Geometric Coefficient of Variation 52.8
Part A Dose 1	AUCinf (PK Part C)	Day 14	839 ng.hour/mL	Geometric Coefficient of Variation 58.9

Secondary

AUClast (PK Part A)

Area under the plasma concentration-time curve from time 0 to time of last measurable concentration. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUClast (PK Part A)	2.56 ng.hour/mL	Geometric Coefficient of Variation 76.1
Part A Dose 1	AUClast (PK Part A)	12.9 ng.hour/mL	Geometric Coefficient of Variation 59.8
Part A Dose 2	AUClast (PK Part A)	153 ng.hour/mL	Geometric Coefficient of Variation 42.8
Part A Dose 3	AUClast (PK Part A)	902 ng.hour/mL	Geometric Coefficient of Variation 63.3
Part A Dose 4	AUClast (PK Part A)	1786 ng.hour/mL	Geometric Coefficient of Variation 41.1
Part A Dose 5	AUClast (PK Part A)	1955 ng.hour/mL	Geometric Coefficient of Variation 45

Secondary

AUClast (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUClast (PK Part C)	Day1	410 ng.hour/mL	Geometric Coefficient of Variation 59
Part A Placebo	AUClast (PK Part C)	Day 14	270 ng.hour/mL	Geometric Coefficient of Variation 67.8
Part A Dose 1	AUClast (PK Part C)	Day1	1034 ng.hour/mL	Geometric Coefficient of Variation 47.5
Part A Dose 1	AUClast (PK Part C)	Day 14	831 ng.hour/mL	Geometric Coefficient of Variation 59.3

Secondary

AUCtau (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	AUCtau (PK Part C)	PM Day 1	231 ng.hour/mL	Geometric Coefficient of Variation 92.5
Part A Placebo	AUCtau (PK Part C)	AM Day 1	210 ng.hour/mL	Geometric Coefficient of Variation 48.3
Part A Placebo	AUCtau (PK Part C)	AM Day 14	254 ng.hour/mL	Geometric Coefficient of Variation 68.9
Part A Dose 1	AUCtau (PK Part C)	AM Day 1	521 ng.hour/mL	Geometric Coefficient of Variation 59.2
Part A Dose 1	AUCtau (PK Part C)	PM Day 1	540 ng.hour/mL	Geometric Coefficient of Variation 53.9
Part A Dose 1	AUCtau (PK Part C)	AM Day 14	792 ng.hour/mL	Geometric Coefficient of Variation 59

Secondary

Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)

Time frame: From Baseline (predose on Day 1) through 72 hours postdose

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Placebo	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 2	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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
Part A Dose 3	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

Secondary

Change From Baseline in Visual Analogue Scale (VAS) (Part B)

The 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.

Time frame: From Baseline (predose on Day 1) through 72 hours postdose

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (72 hours)	-1.8 mm on a 100-mm line (change)	Standard Deviation 8.33
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (2 hours)	6.0 mm on a 100-mm line (change)	Standard Deviation 10.94
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (8 hours)	7.5 mm on a 100-mm line (change)	Standard Deviation 14.87
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (0.5 hour)	2.3 mm on a 100-mm line (change)	Standard Deviation 3.78
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (6 hours)	15.7 mm on a 100-mm line (change)	Standard Deviation 17.51
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (3 hours)	4.7 mm on a 100-mm line (change)	Standard Deviation 6.92
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (1 hour)	1.0 mm on a 100-mm line (change)	Standard Deviation 4.1
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (24 hours)	8.5 mm on a 100-mm line (change)	Standard Deviation 12.18
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (48 hours)	9.5 mm on a 100-mm line (change)	Standard Deviation 10.84
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (4 hours)	8.3 mm on a 100-mm line (change)	Standard Deviation 16.54
Part A Placebo	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (0.25 hour)	-0.7 mm on a 100-mm line (change)	Standard Deviation 2.73
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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
Part A Dose 1	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 6.8
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (72 hours)	-6.0 mm on a 100-mm line (change)	Standard Deviation 10.22
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (0.25 hour)	-3.0 mm on a 100-mm line (change)	Standard Deviation 4.3
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (0.5 hour)	3.0 mm on a 100-mm line (change)	Standard Deviation 14.61
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (1 hour)	16.4 mm on a 100-mm line (change)	Standard Deviation 36.22
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (2 hours)	14.4 mm on a 100-mm line (change)	Standard Deviation 30.07
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (3 hours)	-2.2 mm on a 100-mm line (change)	Standard Deviation 14.58
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (4 hours)	2.2 mm on a 100-mm line (change)	Standard Deviation 18.53
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (6 hours)	10.0 mm on a 100-mm line (change)	Standard Deviation 32.61
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (8 hours)	1.2 mm on a 100-mm line (change)	Standard Deviation 5.31
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (24 hours)	-6.0 mm on a 100-mm line (change)	Standard Deviation 11.58
Part A Dose 2	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (48 hours)	-5.0 mm on a 100-mm line (change)	Standard Deviation 14.21
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (4 hours)	8.6 mm on a 100-mm line (change)	Standard Deviation 16.06
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (72 hours)	-3.0 mm on a 100-mm line (change)	Standard Deviation 3.32
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (24 hours)	6.8 mm on a 100-mm line (change)	Standard Deviation 13.14
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (3 hours)	-2.0 mm on a 100-mm line (change)	Standard Deviation 3.39
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (2 hours)	9.6 mm on a 100-mm line (change)	Standard Deviation 25.44
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (0.25 hour)	-1.6 mm on a 100-mm line (change)	Standard Deviation 1.34
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (48 hours)	3.6 mm on a 100-mm line (change)	Standard Deviation 13.28
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (1 hour)	2.8 mm on a 100-mm line (change)	Standard Deviation 12.56
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (0.5 hour)	-0.2 mm on a 100-mm line (change)	Standard Deviation 2.86
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (8 hours)	0.2 mm on a 100-mm line (change)	Standard Deviation 3.42
Part A Dose 3	Change From Baseline in Visual Analogue Scale (VAS) (Part B)	Score (6 hours)	1.8 mm on a 100-mm line (change)	Standard Deviation 7.98

Secondary

CL/F (PK Part A)

Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	CL/F (PK Part A)	NA L/hour	—
Part A Dose 1	CL/F (PK Part A)	489 L/hour	Standard Deviation 287
Part A Dose 2	CL/F (PK Part A)	139 L/hour	Standard Deviation 65.5
Part A Dose 3	CL/F (PK Part A)	75.0 L/hour	Standard Deviation 36.2
Part A Dose 4	CL/F (PK Part A)	59.4 L/hour	Standard Deviation 21.3
Part A Dose 5	CL/F (PK Part A)	66.4 L/hour	Standard Deviation 31.2

Secondary

CLSS/F (PK Part C)

Systemic clearance relative to bioavailability at steady state (Day 14). Calculated from plasma concentrations measured at the time points below.

Time frame: 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 14

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	CLSS/F (PK Part C)	139 L/hour	Standard Deviation 87.1
Part A Dose 1	CLSS/F (PK Part C)	70.2 L/hour	Standard Deviation 31.5

Secondary

Cmax (PK Part A)

Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	Cmax (PK Part A)	1.10 ng/mL	Geometric Coefficient of Variation 73.9
Part A Dose 1	Cmax (PK Part A)	4.20 ng/mL	Geometric Coefficient of Variation 77.2
Part A Dose 2	Cmax (PK Part A)	43.7 ng/mL	Geometric Coefficient of Variation 40.8
Part A Dose 3	Cmax (PK Part A)	297 ng/mL	Geometric Coefficient of Variation 74.1
Part A Dose 4	Cmax (PK Part A)	548 ng/mL	Geometric Coefficient of Variation 33.1
Part A Dose 5	Cmax (PK Part A)	695 ng/mL	Geometric Coefficient of Variation 54.8

Secondary

Cmax (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part A Placebo	Cmax (PK Part C)	AM Day 1	77.9 ng/mL	Geometric Coefficient of Variation 56
Part A Placebo	Cmax (PK Part C)	PM Day 1	49.5 ng/mL	Geometric Coefficient of Variation 89.2
Part A Placebo	Cmax (PK Part C)	AM Day 14	85.4 ng/mL	Geometric Coefficient of Variation 50
Part A Dose 1	Cmax (PK Part C)	AM Day 1	198 ng/mL	Geometric Coefficient of Variation 47.8
Part A Dose 1	Cmax (PK Part C)	PM Day 1	138 ng/mL	Geometric Coefficient of Variation 47.8
Part A Dose 1	Cmax (PK Part C)	AM Day 14	241 ng/mL	Geometric Coefficient of Variation 49.9

Secondary

Ctrough (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Part A Placebo	Ctrough (PK Part C)	Day 1, 12 hours	0.684 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 2	1.81 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 3	2.97 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 5	2.39 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 7	2.73 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 9	2.87 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 11	1.95 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 13	3.41 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 14	3.24 ng/mL
Part A Placebo	Ctrough (PK Part C)	Day 14, 12 hours	2.19 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 13	4.72 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 1, 12 hours	1.65 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 9	6.97 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 2	3.57 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 14, 12 hours	4.93 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 3	4.68 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 11	4.27 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 5	6.47 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 14	6.28 ng/mL
Part A Dose 1	Ctrough (PK Part C)	Day 7	7.09 ng/mL

Secondary

Rac(AUCtau) (PK Part C)

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	Rac(AUCtau) (PK Part C)	1.33 ratio	Standard Deviation 0.679
Part A Dose 1	Rac(AUCtau) (PK Part C)	1.65 ratio	Standard Deviation 0.84

Secondary

Rac(Cmax) (PK Part C)

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	Rac(Cmax) (PK Part C)	1.22 ratio	Standard Deviation 0.673
Part A Dose 1	Rac(Cmax) (PK Part C)	1.29 ratio	Standard Deviation 0.559

Secondary

SR(AUC) (PK Part C)

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	SR(AUC) (PK Part C)	0.556 ratio	Standard Deviation 0.275
Part A Dose 1	SR(AUC) (PK Part C)	0.733 ratio	Standard Deviation 0.158

Secondary

t1⁄2 (PK Part A)

Terminal half-life. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	t1⁄2 (PK Part A)	NA Hours	—
Part A Dose 1	t1⁄2 (PK Part A)	1.89 Hours	Standard Deviation 0.709
Part A Dose 2	t1⁄2 (PK Part A)	3.50 Hours	Standard Deviation 0.983
Part A Dose 3	t1⁄2 (PK Part A)	4.51 Hours	Standard Deviation 3.41
Part A Dose 4	t1⁄2 (PK Part A)	5.57 Hours	Standard Deviation 5.95
Part A Dose 5	t1⁄2 (PK Part A)	7.12 Hours	Standard Deviation 4.48

Secondary

t1⁄2 (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A Placebo	t1⁄2 (PK Part C)	Day 1	1.68 Hours	Standard Deviation 0.317
Part A Placebo	t1⁄2 (PK Part C)	Day 14	5.89 Hours	Standard Deviation 2.82
Part A Dose 1	t1⁄2 (PK Part C)	Day 1	1.63 Hours	Standard Deviation 0.177
Part A Dose 1	t1⁄2 (PK Part C)	Day 14	9.87 Hours	Standard Deviation 7.35

Secondary

Terminal Rate Constant (PK Part A)

Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	Terminal Rate Constant (PK Part A)	NA /Hour	—
Part A Dose 1	Terminal Rate Constant (PK Part A)	0.419 /Hour	Standard Deviation 0.172
Part A Dose 2	Terminal Rate Constant (PK Part A)	0.214 /Hour	Standard Deviation 0.0702
Part A Dose 3	Terminal Rate Constant (PK Part A)	0.216 /Hour	Standard Deviation 0.107
Part A Dose 4	Terminal Rate Constant (PK Part A)	0.221 /Hour	Standard Deviation 0.127
Part A Dose 5	Terminal Rate Constant (PK Part A)	0.143 /Hour	Standard Deviation 0.1

Secondary

Terminal Rate Constant (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A Placebo	Terminal Rate Constant (PK Part C)	Day 1	0.424 /Hour	Standard Deviation 0.0848
Part A Placebo	Terminal Rate Constant (PK Part C)	Day 14	0.169 /Hour	Standard Deviation 0.148
Part A Dose 1	Terminal Rate Constant (PK Part C)	Day 1	0.428 /Hour	Standard Deviation 0.0428
Part A Dose 1	Terminal Rate Constant (PK Part C)	Day 14	0.123 /Hour	Standard Deviation 0.0955

Secondary

Tmax (PK Part A)

Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (MEDIAN)
Part A Placebo	Tmax (PK Part A)	2.00 Hours
Part A Dose 1	Tmax (PK Part A)	1.50 Hours
Part A Dose 2	Tmax (PK Part A)	2.03 Hours
Part A Dose 3	Tmax (PK Part A)	1.00 Hours
Part A Dose 4	Tmax (PK Part A)	2.00 Hours
Part A Dose 5	Tmax (PK Part A)	1.00 Hours

Secondary

Tmax (PK Part C)

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.

Time frame: 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.

Arm	Measure	Group	Value (MEDIAN)
Part A Placebo	Tmax (PK Part C)	AM Day 1	2.00 Hours
Part A Placebo	Tmax (PK Part C)	PM Day 1	3.03 Hours
Part A Placebo	Tmax (PK Part C)	AM Day 14	2.08 Hours
Part A Dose 1	Tmax (PK Part C)	AM Day 1	1.51 Hours
Part A Dose 1	Tmax (PK Part C)	PM Day 1	3.00 Hours
Part A Dose 1	Tmax (PK Part C)	AM Day 14	2.00 Hours

Secondary

VZ/F (PK Part A)

Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below.

Time frame: 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

Population: PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	VZ/F (PK Part A)	NA L	—
Part A Dose 1	VZ/F (PK Part A)	1268 L	Standard Deviation 747
Part A Dose 2	VZ/F (PK Part A)	666 L	Standard Deviation 241
Part A Dose 3	VZ/F (PK Part A)	384 L	Standard Deviation 147
Part A Dose 4	VZ/F (PK Part A)	374 L	Standard Deviation 227
Part A Dose 5	VZ/F (PK Part A)	720 L	Standard Deviation 549

Secondary

VZ/F (PK Part C)

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Part A Placebo	VZ/F (PK Part C)	1221 L	Standard Deviation 823
Part A Dose 1	VZ/F (PK Part C)	977 L	Standard Deviation 874

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Study Investigating the Safety, Tolerability, PK and Food Effect of BEN8744.

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Intervention model description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

AUC24 (PK Part B)

AUC72 (PK Part B)

%AUCextrap (PK Part B)

AUCinf (PK Part B)

AUClast (PK Part B)

Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)

Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)

Change From Baseline in Visual Analogue Scale (VAS) (Part A)

Change From Baseline in Visual Analogue Scale (VAS) (Part C)

CL/F (PK Part B)

Cmax (PK Part B)

Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)

t1⁄2 (PK Part B)

Terminal Rate Constant (PK Part B)

Tmax (PK Part B)

VZ/F (PK Part B)

AUC24 (PK Part A)

AUC72 (PK Part A)

AUC72 (PK Part C)

%AUCextrap (PK Part A)

%AUCextrap (PK Part C)

AUCinf (PK Part A)

AUCinf (PK Part C)

AUClast (PK Part A)

AUClast (PK Part C)

AUCtau (PK Part C)

Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)

Change From Baseline in Visual Analogue Scale (VAS) (Part B)

CL/F (PK Part A)

CLSS/F (PK Part C)

Cmax (PK Part A)

Cmax (PK Part C)

Ctrough (PK Part C)

Rac(AUCtau) (PK Part C)

Rac(Cmax) (PK Part C)

SR(AUC) (PK Part C)

t1⁄2 (PK Part A)

t1⁄2 (PK Part C)

Terminal Rate Constant (PK Part A)

Terminal Rate Constant (PK Part C)

Tmax (PK Part A)

Tmax (PK Part C)

VZ/F (PK Part A)

VZ/F (PK Part C)