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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.
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
A1- 2mg A2- 6mg A3- 20mg A4- 60mg A5- 100mg A6 (optional) - 120mg
For Part B
For Part C:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A Dose 1 | Experimental | Part A Dose 1 Single dose of 2 mg BEN8744 |
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| Part A Dose 2 | Experimental | Part A Dose 2 Single dose of 6 mg BEN8744 |
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| Part A Dose 3 | Experimental | Part A Dose 3 Single dose of 20 mg BEN8744 |
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| Part A Dose 4 | Experimental | Part A Dose 4 Single dose of 60 mg BEN8744 |
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| Part A Dose 5 | Experimental | Part A Dose 5 Single dose of 100 mg BEN8744 |
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| Part A Dose 6 | Experimental | Part A Dose 6 Single dose of 120 mg BEN8744 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BEN8744 | Drug | Formulated powder in capsule for oral administration. Supplied as filled Size 0 Swedish Orange capsule. Doses: 2mg, 10mg and 40mg. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | From Baseline (predose on Day 1) through 72 hours postdose |
| 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. | From Baseline (predose on Day 1) through 72 hours postdose |
| Cmax (PK Part B) | Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below. | 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) |
| Tmax (PK Part B) | Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below. | 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) |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax (PK Part A) | Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below. | 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 |
| Tmax (PK Part A) |
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Inclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Denisa Wilkes | Hammersmith Medicine Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hammersmith Medicines Research | London | United Kingdom |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A Placebo | Single dose of placebo capsule(s) matched to active dose |
| FG001 | Part A Dose 1 | Single 2 mg dose of BEN8744 |
| FG002 | Part A Dose 2 | Single 6 mg dose of BEN8744 |
| FG003 | Part A Dose 3 | Single 20 mg dose of BEN8744 |
| FG004 | Part A Dose 4 | Single 60 mg dose of BEN8744 |
| FG005 | Part A Dose 5 | Single 100 mg dose of BEN8744 |
| FG006 | Part A Dose 6 | Single 120 mg dose of BEN8744 |
| FG007 | Part B Dose 1 | Single 30 mg dose of BEN8744 administered after 10-hour fast and after high-fat breakfast |
| FG008 | Part B Dose 2 | Single 50 mg dose of BEN8744 administered after 10-hour fast and after high-fat breakfast |
| FG009 | Part C Placebo | Placebo capsules matched to active dose twice-daily for 14 days |
| FG010 | Part C Dose 1 | 30 mg BEN8744 twice-daily for 14 days |
| FG011 | Part C Dose 2 | 50 mg BEN8744 twice-daily for 14 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A Placebo | Single dose of placebo capsule(s) matched to active dose |
| BG001 | Part A Dose 1 | Single 2 mg dose of BEN8744 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | score on a scale (change) | From Baseline (predose on Day 1) through 72 hours postdose |
|
From the signing of the informed consent form through 10 days after the last dose (Day 11 in Parts A and B, Day 24 in Part C)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A Placebo | Single dose of placebo capsule(s) matched to active dose | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Judit Molnar, MD, PhD | Benevolent | +44 20 3781 9360 | judit.molnar.md@benevolent.ai |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 11, 2023 | Feb 5, 2025 | Prot_SAP_000.pdf |
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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
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| Part A placebo | Experimental | Part A placebo Single dose of placebo |
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| Part B Dose 1 fed | Experimental | Part B Dose 1 Fed Single dose of BEN8744 after high-fat meal (Dose 30mg QD) |
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| Part B Dose 1 Fasted | Experimental | Part B Dose 1 Fasted Single dose of BEN8744 after 10 hours fasting (Dose 30mg QD) |
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| Part B Dose 2 Fed | Experimental | Part B Dose 2 Fed Single dose of BEN8744 after high-fat meal (Dose 50mg QD) |
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| Part B Dose 2 Fasted | Experimental | Part B Dose 2 Fasted Single dose of BEN8744 after 10 hours fasting (Dose 50mg QD) |
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| Part C Dose 1 | Experimental | Part C Dose 1 14 daily doses of BEN8744 (Dose 30mg BID) |
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| Part C Dose 2 | Experimental | Part C Dose 2 14 daily doses of BEN8744 (Dose 50mg BID) |
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| Part C placebo | Experimental | Part C placebo 14 daily doses of placebo |
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| Matching Placebo | Drug | Formulated powder in capsule for oral administration. Supplied as filled Size 0 Swedish Orange capsule. Doses: 2mg, 10mg and 40mg. |
|
| 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) |
| 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. | 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) |
| 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. | 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) |
| AUCinf (PK Part B) | Area under the plasma concentration-time curve from time 0 to infinity. Calculated from plasma concentrations at time points below. | 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) |
| t1⁄2 (PK Part B) | Terminal half-life. Calculated from plasma concentrations at time points below. | 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 Rate Constant (PK Part B) | Calculated from plasma concentrations at time points below. | 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) |
| CL/F (PK Part B) | Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below. | 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) |
| VZ/F (PK Part B) | Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below. | 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) |
| %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. | 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) |
| Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C) | 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. | From Baseline (predose on Day 1) through 48 hours postdose |
| 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. | From Baseline (predose on Day 1) through 48 hours postdose |
| 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. | Completed during screening and on Days 17 and 24 |
Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below. |
| 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 |
| 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. | Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours postdose |
| 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. | 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 |
| 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. | 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 |
| AUCinf (PK Part A) | Area under the plasma concentration-time curve from time 0 to infinity. Calculated from plasma concentrations at time points below. | 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 |
| %AUCextrap (PK Part A) | Percentage of AUCinf extrapolated from time of last measurable concentration to infinity. Calculated from plasma concentrations at time points below. | 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 |
| t1⁄2 (PK Part A) | Terminal half-life. Calculated from plasma concentrations at time points below. | 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 Rate Constant (PK Part A) | Calculated from plasma concentrations at time points below. | 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 |
| CL/F (PK Part A) | Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below. | 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 |
| VZ/F (PK Part A) | Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below. | 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 |
| Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B) | 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. | From Baseline (predose on Day 1) through 72 hours postdose |
| 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. | From Baseline (predose on Day 1) through 72 hours postdose |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | 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 |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| %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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | 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 |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| 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. | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
| Out-of-range blood tests |
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| BG002 | Part A Dose 2 | Single 6 mg dose of BEN8744 |
| BG003 | Part A Dose 3 | Single 20 mg dose of BEN8744 |
| BG004 | Part A Dose 4 | Single 60 mg dose of BEN8744 |
| BG005 | Part A Dose 5 | Single 100 mg dose of BEN8744 |
| BG006 | Part A Dose 6 | Single 120 mg dose of BEN8744 |
| BG007 | 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 |
| BG008 | Part C Placebo | Placebo capsules matched to active dose twice-daily for 14 days |
| BG009 | Part C Dose 1 | 30 mg BEN8744 twice-daily for 14 days |
| BG010 | Part C Dose 2 | 50 mg BEN8744 twice-daily for 14 days |
| BG011 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Part A Dose 1 |
Single 2 mg dose of BEN8744 |
| OG002 | Part A Dose 2 | Single 6 mg dose of BEN8744 |
| OG003 | Part A Dose 3 | Single 20 mg dose of BEN8744 |
| OG004 | Part A Dose 4 | Single 60 mg dose BEN8744 |
| OG005 | Part A Dose 5 | Single 100 mg dose of BEN8744 |
| OG006 | Part A Dose 6 | Single 120 mg dose of BEN8744 |
|
|
| 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. | Posted | Mean | Standard Deviation | mm on a 100-mm line (change) | From Baseline (predose on Day 1) through 72 hours postdose |
|
|
|
| Primary | Cmax (PK Part B) | Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
|
|
|
| Primary | Tmax (PK Part B) | Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below. | Posted | Median | Full Range | Hours | 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) |
|
|
|
| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | 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) |
|
|
|
| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | 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) |
|
|
|
| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | 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) |
|
|
|
| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | 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) |
|
|
|
| Primary | t1⁄2 (PK Part B) | Terminal half-life. Calculated from plasma concentrations at time points below. | Posted | Mean | Standard Deviation | Hours | 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) |
|
|
|
| Primary | Terminal Rate Constant (PK Part B) | Calculated from plasma concentrations at time points below. | Posted | Mean | Standard Deviation | /hour | 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) |
|
|
|
| Primary | CL/F (PK Part B) | Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below. | Posted | Mean | Standard Deviation | L/hour | 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) |
|
|
|
| Primary | VZ/F (PK Part B) | Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below. | Posted | Mean | Standard Deviation | L | 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) |
|
|
|
| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of AUC | 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) |
|
|
|
| Primary | Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C) | 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. | Posted | Mean | Standard Deviation | score on a scale (change) | From Baseline (predose on Day 1) through 48 hours postdose |
|
|
|
| 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. | Posted | Mean | Standard Deviation | mm on a 100-mm line (change) | From Baseline (predose on Day 1) through 48 hours postdose |
|
|
|
| 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. | Posted | Count of Participants | Participants | Completed during screening and on Days 17 and 24 |
|
|
|
| Secondary | Cmax (PK Part A) | Maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
|
|
|
| Secondary | Tmax (PK Part A) | Time to reach maximum (peak) plasma concentration. Calculated from plasma concentrations at time points below. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Median | Full Range | Hours | 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 |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours postdose |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | 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 |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | 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 |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | 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 |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of AUC | 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 |
|
|
|
| Secondary | t1⁄2 (PK Part A) | Terminal half-life. Calculated from plasma concentrations at time points below. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | Hours | 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 |
|
|
|
| Secondary | Terminal Rate Constant (PK Part A) | Calculated from plasma concentrations at time points below. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | /Hour | 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 |
|
|
|
| Secondary | CL/F (PK Part A) | Systemic clearance relative to absolute bioavailability. Calculated from plasma concentrations at time points below. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | L/hour | 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 |
|
|
|
| Secondary | VZ/F (PK Part A) | Apparent volume of distribution relative to absolute bioavailability. Calculated from plasma concentrations at time points below. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | L | 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 |
|
|
|
| Secondary | Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B) | 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. | Posted | Mean | Standard Deviation | score on a scale (change) | From Baseline (predose on Day 1) through 72 hours postdose |
|
|
|
| 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. | Posted | Mean | Standard Deviation | mm on a 100-mm line (change) | From Baseline (predose on Day 1) through 72 hours postdose |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Median | Full Range | Hours | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | 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 |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | Hours | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng.hour/mL | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of AUC | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | /Hour | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | L/hour | 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 |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | L | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | ratio | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
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|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | ratio | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 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. | PK analysis conducted with data from participants who received active BEN8774; plasma PK samples from participants in the placebo group were not tested. | Posted | Mean | Standard Deviation | ratio | Plasma concentrations measured from predose on Day 1 through 72 hours after Day 14 dose (see specific time points above) |
|
|
|
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Part A Dose 1 | Single 2 mg dose of BEN8744 | 0 | 6 | 0 | 6 | 1 | 6 |
| EG002 | Part A Dose 2 | Single 6 mg dose of BEN8744 | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | Part A Dose 3 | Single 20 mg dose of BEN8744 | 0 | 6 | 0 | 6 | 4 | 6 |
| EG004 | Part A Dose 4 | Single 60 mg dose of BEN8744 | 0 | 6 | 0 | 6 | 2 | 6 |
| EG005 | Part A Dose 5 | Single 100 mg dose of BEN8744 | 0 | 6 | 0 | 6 | 2 | 6 |
| EG006 | Part A Dose 6 | Single 120 mg dose of BEN8744 | 0 | 6 | 0 | 6 | 1 | 6 |
| EG007 | Part B Dose 1 Fasted | Single 30 mg dose of BEN8744 after 10-hour fast | 0 | 6 | 0 | 6 | 1 | 6 |
| EG008 | Part B Dose 1 Fed | Single 30 mg dose of BEN8744 after a high-fat breakfast | 0 | 6 | 0 | 6 | 1 | 6 |
| EG009 | Part B Dose 2 Fasted | Single 50 mg dose of BEN8744 after 10-hour fast | 0 | 5 | 0 | 5 | 0 | 5 |
| EG010 | Part B Dose 2 Fed | Single 50 mg dose of BEN8744 after a high-fat breakfast | 0 | 5 | 0 | 5 | 2 | 5 |
| EG011 | Part C Placebo | Placebo capsules matched to active dose twice-daily for 14 days | 0 | 4 | 0 | 4 | 3 | 4 |
| EG012 | Part C Dose 1 | 30 mg BEN8744 twice-daily for 14 days | 0 | 6 | 0 | 6 | 1 | 6 |
| EG013 | Part C Dose 2 | 50 mg BEN8744 twice-daily for 14 days | 0 | 6 | 0 | 6 | 2 | 6 |
| Gastrooesophageal reflux | Gastrointestinal disorders | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Hepatic enzymes increased | Investigations | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Costochondritis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Eczema asteatotic | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
Not provided
| Score (0.5 hour) |
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| Score (1 hour) |
|
| Score (2 hours) |
|
| Score (3 hours) |
|
| Score (4 hours) |
|
| Score (6 hours) |
|
| Score (8 hours) |
|
| Score (24 hours) |
|
| Score (48 hours) |
|
| Score (72 hours) |
|
|
| Composite score (1 hour) |
|
| Composite score (2 hours) |
|
| Composite score (3 hours) |
|
| Composite score (4 hours) |
|
| Composite score (6 hours) |
|
| Composite score (8 hours) |
|
| Composite score (24 hours) |
|
| Composite score (48 hours) |
|
| Sum (0.25 hour) |
|
| Sum (0.5 hour) |
|
| Sum (1 hour) |
|
| Sum (2 hours) |
|
| Sum (3 hours) |
|
| Sum (4 hours) |
|
| Sum (6 hours) |
|
| Sum (8 hours) |
|
| Sum (24 hours) |
|
| Sum (48 hours) |
|
|
| Score (1 hour) |
|
| Score (2 hours) |
|
| Score (3 hours) |
|
| Score (4 hours) |
|
| Score (6 hours) |
|
| Score (8 hours) |
|
| Score (24 hours) |
|
| Score (48 hours) |
|
|
| Composite score (0.5 hour) |
|
| Composite score (1 hour) |
|
| Composite score (2 hours) |
|
| Composite score (3 hours) |
|
| Composite score (4 hours) |
|
| Composite score (6 hours) |
|
| Composite score (8 hours) |
|
| Composite score (24 hours) |
|
| Composite score (48 hours) |
|
| Composite score (72 hours) |
|
| Sum (0.25 hour) |
|
| Sum (0.5 hour) |
|
| Sum (1 hour) |
|
| Sum (2 hours) |
|
| Sum (3 hours) |
|
| Sum (4 hours) |
|
| Sum (6 hours) |
|
| Sum (8 hours) |
|
| Sum (24 hours) |
|
| Sum (48 hours) |
|
| Sum (72 hours) |
|
| Score (0.5 hour) |
|
| Score (1 hour) |
|
| Score (2 hours) |
|
| Score (3 hours) |
|
| Score (4 hours) |
|
| Score (6 hours) |
|
| Score (8 hours) |
|
| Score (24 hours) |
|
| Score (48 hours) |
|
| Score (72 hours) |
|
| AM Day 14 |
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| AM Day 14 |
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| Day 3 |
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| Day 5 |
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| Day 7 |
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| Day 9 |
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| Day 11 |
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| Day 13 |
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| Day 14 |
|
| Day 14, 12 hours |
|
| AM Day 14 |
|