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CompletedNCT06118385Updated May 7, 2025Results posted

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

A Phase 1 interventional study of BEN8744 and Matching Placebo in Healthy Volunteer Study, sponsored by BenevolentAI Bio. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-05-07.

Sponsored by BenevolentAI Bio · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
76
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

  • Healthy Volunteer Study
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
76 participants (actual)

Study arms

  • Experimental
    Part A Dose 1

    Part A Dose 1 Single dose of 2 mg BEN8744

    Drug: BEN8744

  • Experimental
    Part A Dose 2

    Part A Dose 2 Single dose of 6 mg BEN8744

    Drug: BEN8744

  • Experimental
    Part A Dose 3

    Part A Dose 3 Single dose of 20 mg BEN8744

    Drug: BEN8744

  • Experimental
    Part A Dose 4

    Part A Dose 4 Single dose of 60 mg BEN8744

    Drug: BEN8744

  • Experimental
    Part A Dose 5

    Part A Dose 5 Single dose of 100 mg BEN8744

    Drug: BEN8744

  • Experimental
    Part A Dose 6

    Part A Dose 6 Single dose of 120 mg BEN8744

    Drug: BEN8744

  • Experimental
    Part A placebo

    Part A placebo Single dose of placebo

    Drug: Matching Placebo

  • Experimental
    Part B Dose 1 fed

    Part B Dose 1 Fed Single dose of BEN8744 after high-fat meal (Dose 30mg QD)

    Drug: BEN8744

  • Experimental
    Part B Dose 1 Fasted

    Part B Dose 1 Fasted Single dose of BEN8744 after 10 hours fasting (Dose 30mg QD)

    Drug: BEN8744

  • Experimental
    Part B Dose 2 Fed

    Part B Dose 2 Fed Single dose of BEN8744 after high-fat meal (Dose 50mg QD)

    Drug: BEN8744

  • Experimental
    Part B Dose 2 Fasted

    Part B Dose 2 Fasted Single dose of BEN8744 after 10 hours fasting (Dose 50mg QD)

    Drug: BEN8744

  • Experimental
    Part C Dose 1

    Part C Dose 1 14 daily doses of BEN8744 (Dose 30mg BID)

    Drug: BEN8744

  • Experimental
    Part C Dose 2

    Part C Dose 2 14 daily doses of BEN8744 (Dose 50mg BID)

    Drug: BEN8744

  • Experimental
    Part C placebo

    Part C placebo 14 daily doses of placebo

    Drug: Matching Placebo

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.

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. 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)

  12. 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)

  13. %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)

  14. 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.

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

  15. 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

  16. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. %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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

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

  13. 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

  14. 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)

  15. 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)

  16. 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)

  17. 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)

  18. 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)

  19. 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

  20. 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)

  21. 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)

  22. %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)

  23. 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)

  24. 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

  25. 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)

  26. 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)

  27. 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)

  28. 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)

06

Results

Posted May 7, 2025

Participant flow

Participant flow — Overall Study
MilestonePart A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6Part B Dose 1Part B Dose 2Part C PlaceboPart C Dose 1Part C Dose 2
Started1266666666466
Completed1266666664466
Not completed000000002000
Withdrew: Protocol violation000000001000
Withdrew: Out-of-range blood tests000000001000

Outcome measures

PrimaryChange 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
Reported as:
Mean · score on a scale (change)
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part A)
score on a scale (change)Part A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
Composite score (0.25 hour)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (0.5 hour)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (1 hour)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (2 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (3 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (4 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (6 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (8 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (24 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (48 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Composite score (72 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (0.25 hour)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (0.5 hour)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (1 hour)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (2 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (3 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (4 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (6 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (8 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (24 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (48 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
Sum (72 hours)0 ± 00 ± 00 ± 00 ± 00 ± 00 ± 00 ± 0
PrimaryChange 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
Reported as:
Mean · mm on a 100-mm line (change)
Change From Baseline in Visual Analogue Scale (VAS) (Part A)
mm on a 100-mm line (change)Part A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
Score (0.25 hour)1.8 ± 4.59-3.0 ± 7.290.5 ± 4.323.7 ± 7.37-1.2 ± 1.94-5.8 ± 7.73-5.5 ± 19.42
Score (0.5 hour)0.3 ± 5.800.5 ± 12.763.8 ± 17.292.7 ± 13.981.0 ± 3.79-2.8 ± 9.52-3.3 ± 35.30
Score (1 hour)1.9 ± 4.64-8.2 ± 13.0614.8 ± 30.646.3 ± 12.861.8 ± 7.14-2.0 ± 7.38-2.0 ± 37.83
Score (2 hours)6.7 ± 12.03-9.3 ± 12.696.2 ± 8.332.0 ± 12.931.3 ± 5.850.7 ± 8.524.0 ± 38.76
Score (3 hours)3.5 ± 9.11-10.3 ± 22.003.7 ± 6.594.3 ± 17.20-1.2 ± 6.623.3 ± 7.66-4.7 ± 30.69
Score (4 hours)1.2 ± 11.44-11.2 ± 14.333.7 ± 8.521.2 ± 14.66-2.3 ± 4.506.8 ± 10.465.0 ± 28.87
Score (6 hours)1.8 ± 7.00-14.3 ± 15.913.5 ± 7.234.3 ± 27.987.0 ± 19.831.5 ± 17.03-2.2 ± 34.74
Score (8 hours)2.1 ± 9.583.7 ± 30.060.0 ± 2.377.3 ± 24.36-2.2 ± 7.688.0 ± 17.20-7.8 ± 28.53
Score (24 hours)-0.4 ± 10.32-5.7 ± 10.95-1.0 ± 6.54-3.3 ± 9.830.5 ± 8.48-2.7 ± 10.86-11.5 ± 31.86
Score (48 hours)-2.5 ± 9.99-10.3 ± 11.67-2.5 ± 5.47-4.0 ± 10.30-2.0 ± 8.69-6.5 ± 13.43-2.8 ± 32.46
Score (72 hours)-4.1 ± 10.30-15.7 ± 16.17-2.3 ± 5.54-4.5 ± 9.59-3.7 ± 7.00-9.3 ± 15.21-6.5 ± 33.41
PrimaryCmax (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)
Reported as:
Geometric mean · ng/mL
Cmax (PK Part B)
ng/mLPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
Cmax (PK Part B)76.7 ± 41.488.8 ± 33.2265 ± 50.0173 ± 56.3
PrimaryTmax (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)
Reported as:
Median · Hours
Tmax (PK Part B)
HoursPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
Tmax (PK Part B)1.08 (1.00 to 3.00)2.02 (1.00 to 3.00)1.00 (0.500 to 2.03)3.00 (2.02 to 4.00)
PrimaryAUC24 (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)
Reported as:
Geometric mean · ng.hour/mL
AUC24 (PK Part B)
ng.hour/mLPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
AUC24 (PK Part B)227 ± 25.0332 ± 25.2721 ± 47.9666 ± 54.3
PrimaryAUC72 (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)
Reported as:
Geometric mean · ng.hour/mL
AUC72 (PK Part B)
ng.hour/mLPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
AUC72 (PK Part B)229 ± 24.3335 ± 26.0723 ± 48.4669 ± 54.9
PrimaryAUClast (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)
Reported as:
Geometric mean · ng.hour/mL
AUClast (PK Part B)
ng.hour/mLPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
AUClast (PK Part B)226 ± 24.8332 ± 25.7721 ± 48.5667 ± 54.9
PrimaryAUCinf (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)
Reported as:
Geometric mean · ng.hour/mL
AUCinf (PK Part B)
ng.hour/mLPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
AUCinf (PK Part B)228 ± 24.4335 ± 26.1723 ± 48.5669 ± 55.0
Primaryt1⁄2 (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)
Reported as:
Mean · Hours
t1⁄2 (PK Part B)
HoursPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
t1⁄2 (PK Part B)4.12 ± 2.264.83 ± 3.674.23 ± 5.143.83 ± 4.69
PrimaryTerminal 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)
Reported as:
Mean · /hour
Terminal Rate Constant (PK Part B)
/hourPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
Terminal Rate Constant (PK Part B)0.210 ± 0.09560.217 ± 0.1320.300 ± 0.1440.340 ± 0.173
PrimaryCL/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)
Reported as:
Mean · L/hour
CL/F (PK Part B)
L/hourPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
CL/F (PK Part B)135 ± 33.792.0 ± 22.775.1 ± 34.382.3 ± 36.4
PrimaryVZ/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)
Reported as:
Mean · L
VZ/F (PK Part B)
LPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
VZ/F (PK Part B)846 ± 582550 ± 268327 ± 218310 ± 186
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)
Reported as:
Geometric mean · Percentage of AUC
%AUCextrap (PK Part B)
Percentage of AUCPart B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
%AUCextrap (PK Part B)0.991 ± 70.20.638 ± 73.10.156 ± 129.40.198 ± 78.0
PrimaryChange 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.

Time frame:
From Baseline (predose on Day 1) through 48 hours postdose
Reported as:
Mean · score on a scale (change)
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part C)
score on a scale (change)Part C PlaceboPart C Dose 1Part C Dose 2
Composite score (0.25 hour)0 ± 00 ± 00 ± 0
Composite score (0.5 hour)0 ± 00 ± 00 ± 0
Composite score (1 hour)0 ± 00 ± 00 ± 0
Composite score (2 hours)0 ± 00 ± 00 ± 0
Composite score (3 hours)0 ± 00 ± 00 ± 0
Composite score (4 hours)0 ± 00 ± 00 ± 0
Composite score (6 hours)0 ± 00 ± 00 ± 0
Composite score (8 hours)0 ± 00 ± 00 ± 0
Composite score (24 hours)0 ± 00 ± 00 ± 0
Composite score (48 hours)0 ± 00 ± 00 ± 0
Sum (0.25 hour)0 ± 00 ± 00 ± 0
Sum (0.5 hour)0 ± 00 ± 00 ± 0
Sum (1 hour)0 ± 00 ± 00 ± 0
Sum (2 hours)0 ± 00 ± 00 ± 0
Sum (3 hours)0 ± 00 ± 00 ± 0
Sum (4 hours)0 ± 00 ± 00 ± 0
Sum (6 hours)0 ± 00 ± 00 ± 0
Sum (8 hours)0 ± 00 ± 00 ± 0
Sum (24 hours)0 ± 00 ± 00 ± 0
Sum (48 hours)0 ± 00 ± 00 ± 0
PrimaryChange 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
Reported as:
Mean · mm on a 100-mm line (change)
Change From Baseline in Visual Analogue Scale (VAS) (Part C)
mm on a 100-mm line (change)Part C PlaceboPart C Dose 1Part C Dose 2
Score (0.25 hour)1.0 ± 3.562.2 ± 13.33-0.3 ± 5.96
Score (0.5 hour)2.5 ± 9.292.7 ± 14.021.8 ± 6.11
Score (1 hour)27.3 ± 24.7315.8 ± 31.914.0 ± 15.66
Score (2 hours)18.8 ± 24.4313.0 ± 26.487.2 ± 17.85
Score (3 hours)18.0 ± 32.1411.0 ± 30.337.3 ± 16.82
Score (4 hours)15.3 ± 27.048.2 ± 21.031.5 ± 9.27
Score (6 hours)7.3 ± 22.535.3 ± 18.686.3 ± 16.43
Score (8 hours)1.0 ± 9.637.3 ± 18.55-2.5 ± 8.07
Score (24 hours)25.8 ± 25.9112.2 ± 18.367.2 ± 24.68
Score (48 hours)8.0 ± 6.983.2 ± 11.962.0 ± 11.37
PrimaryColumbia-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
Reported as:
Count of participants · Participants
Columbia-Suicide Severity Rating Scale (C-SSRS) (Part C)
ParticipantsPart C PlaceboPart C Dose 1Part C Dose 2
No or low risk - Day 17466
No or low risk - Day 24466
SecondaryCmax (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
Reported as:
Geometric mean · ng/mL
Cmax (PK Part A)
ng/mLPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
Cmax (PK Part A)1.10 ± 73.94.20 ± 77.243.7 ± 40.8297 ± 74.1548 ± 33.1695 ± 54.8
SecondaryTmax (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
Reported as:
Median · Hours
Tmax (PK Part A)
HoursPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
Tmax (PK Part A)2.00 (1.98 to 2.05)1.50 (0.517 to 3.00)2.03 (1.03 to 3.03)1.00 (1.00 to 2.00)2.00 (1.00 to 3.00)1.00 (1.00 to 3.00)
SecondaryAUC24 (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
Reported as:
Geometric mean · ng.hour/mL
AUC24 (PK Part A)
ng.hour/mLPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
AUC24 (PK Part A)NA ± NA13.8 ± 54.1154 ± 42.2901 ± 62.91781 ± 40.61949 ± 45.1
SecondaryAUC72 (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
Reported as:
Geometric mean · ng.hour/mL
AUC72 (PK Part A)
ng.hour/mLPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
AUC72 (PK Part A)NA ± NA13.9 ± 54.2155 ± 42.4904 ± 63.31788 ± 41.11959 ± 44.8
SecondaryAUClast (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
Reported as:
Geometric mean · ng.hour/mL
AUClast (PK Part A)
ng.hour/mLPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
AUClast (PK Part A)2.56 ± 76.112.9 ± 59.8153 ± 42.8902 ± 63.31786 ± 41.11955 ± 45.0
SecondaryAUCinf (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
Reported as:
Geometric mean · ng.hour/mL
AUCinf (PK Part A)
ng.hour/mLPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
AUCinf (PK Part A)NA ± NA13.8 ± 53.9155 ± 42.4904 ± 63.31788 ± 41.21959 ± 44.8
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
Reported as:
Geometric mean · Percentage of AUC
%AUCextrap (PK Part A)
Percentage of AUCPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
%AUCextrap (PK Part A)6.62 ± NA4.95 ± 76.20.910 ± 69.80.202 ± 126.70.0796 ± 125.80.108 ± 236.0
Secondaryt1⁄2 (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
Reported as:
Mean · Hours
t1⁄2 (PK Part A)
HoursPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
t1⁄2 (PK Part A)NA ± NA1.89 ± 0.7093.50 ± 0.9834.51 ± 3.415.57 ± 5.957.12 ± 4.48
SecondaryTerminal 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
Reported as:
Mean · /Hour
Terminal Rate Constant (PK Part A)
/HourPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
Terminal Rate Constant (PK Part A)NA ± NA0.419 ± 0.1720.214 ± 0.07020.216 ± 0.1070.221 ± 0.1270.143 ± 0.100
SecondaryCL/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
Reported as:
Mean · L/hour
CL/F (PK Part A)
L/hourPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
CL/F (PK Part A)NA ± NA489 ± 287139 ± 65.575.0 ± 36.259.4 ± 21.366.4 ± 31.2
SecondaryVZ/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
Reported as:
Mean · L
VZ/F (PK Part A)
LPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6
VZ/F (PK Part A)NA ± NA1268 ± 747666 ± 241384 ± 147374 ± 227720 ± 549
SecondaryChange 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.

Time frame:
From Baseline (predose on Day 1) through 72 hours postdose
Reported as:
Mean · score on a scale (change)
Change From Baseline in Observer's Assessment of Alertness/Sedation Scale (OAAS/S) (Part B)
score on a scale (change)Part B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
Composite score (0.25 hour)0 ± 00 ± 00 ± 00 ± 0
Composite score (0.5 hour)0 ± 00 ± 00 ± 00 ± 0
Composite score (1 hour)0 ± 00 ± 00 ± 00 ± 0
Composite score (2 hours)0 ± 00 ± 00 ± 00 ± 0
Composite score (3 hours)0 ± 00 ± 00 ± 00 ± 0
Composite score (4 hours)0 ± 00 ± 00 ± 00 ± 0
Composite score (6 hours)0 ± 00 ± 00 ± 00 ± 0
Composite score (8 hours)0 ± 00 ± 00 ± 00 ± 0
Composite score (24 hours)0 ± 00 ± 00 ± 00 ± 0
Composite score (48 hours)0 ± 00 ± 00 ± 00 ± 0
Composite score (72 hours)0 ± 00 ± 00 ± 00 ± 0
Sum (0.25 hour)0 ± 00 ± 00 ± 00 ± 0
Sum (0.5 hour)0 ± 00 ± 00 ± 00 ± 0
Sum (1 hour)0 ± 00 ± 00 ± 00 ± 0
Sum (2 hours)0 ± 00 ± 00 ± 00 ± 0
Sum (3 hours)0 ± 00 ± 00 ± 00 ± 0
Sum (4 hours)0 ± 00 ± 00 ± 00 ± 0
Sum (6 hours)0 ± 00 ± 00 ± 00 ± 0
Sum (8 hours)0 ± 00 ± 00 ± 00 ± 0
Sum (24 hours)0 ± 00 ± 00 ± 00 ± 0
Sum (48 hours)0 ± 00 ± 00 ± 00 ± 0
Sum (72 hours)0 ± 00 ± 00 ± 00 ± 0
SecondaryChange 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
Reported as:
Mean · mm on a 100-mm line (change)
Change From Baseline in Visual Analogue Scale (VAS) (Part B)
mm on a 100-mm line (change)Part B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 Fed
Score (0.25 hour)-0.7 ± 2.731.7 ± 6.80-3.0 ± 4.30-1.6 ± 1.34
Score (0.5 hour)2.3 ± 3.788.0 ± 12.793.0 ± 14.61-0.2 ± 2.86
Score (1 hour)1.0 ± 4.106.2 ± 12.0916.4 ± 36.222.8 ± 12.56
Score (2 hours)6.0 ± 10.946.7 ± 14.0814.4 ± 30.079.6 ± 25.44
Score (3 hours)4.7 ± 6.925.0 ± 17.81-2.2 ± 14.58-2.0 ± 3.39
Score (4 hours)8.3 ± 16.548.3 ± 10.892.2 ± 18.538.6 ± 16.06
Score (6 hours)15.7 ± 17.517.0 ± 19.2910.0 ± 32.611.8 ± 7.98
Score (8 hours)7.5 ± 14.879.8 ± 15.841.2 ± 5.310.2 ± 3.42
Score (24 hours)8.5 ± 12.187.7 ± 11.89-6.0 ± 11.586.8 ± 13.14
Score (48 hours)9.5 ± 10.843.5 ± 9.27-5.0 ± 14.213.6 ± 13.28
Score (72 hours)-1.8 ± 8.332.3 ± 9.46-6.0 ± 10.22-3.0 ± 3.32
SecondaryCmax (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)
Reported as:
Geometric mean · ng/mL
Cmax (PK Part C)
ng/mLPart C Dose 1Part C Dose 2
AM Day 177.9 ± 56.0198 ± 47.8
PM Day 149.5 ± 89.2138 ± 47.8
AM Day 1485.4 ± 50.0241 ± 49.9
SecondaryTmax (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)
Reported as:
Median · Hours
Tmax (PK Part C)
HoursPart C Dose 1Part C Dose 2
AM Day 12.00 (0.500 to 2.00)1.51 (1.00 to 2.00)
PM Day 13.03 (1.00 to 7.95)3.00 (2.00 to 4.00)
AM Day 142.08 (1.00 to 3.02)2.00 (1.00 to 3.00)
SecondaryCtrough (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)
Reported as:
Geometric mean · ng/mL
Ctrough (PK Part C)
ng/mLPart C Dose 1Part C Dose 2
Day 1, 12 hours0.684 (0.385 to 1.22)1.65 (0.865 to 3.16)
Day 21.81 (0.875 to 3.75)3.57 (1.70 to 7.53)
Day 32.97 (1.22 to 7.23)4.68 (1.78 to 12.3)
Day 52.39 (0.978 to 5.83)6.47 (2.61 to 16.1)
Day 72.73 (1.43 to 5.21)7.09 (3.07 to 16.4)
Day 92.87 (0.907 to 9.09)6.97 (3.63 to 13.4)
Day 111.95 (0.647 to 5.90)4.27 (2.03 to 9.01)
Day 133.41 (1.46 to 7.98)4.72 (2.18 to 10.2)
Day 143.24 (1.35 to 7.78)6.28 (3.34 to 11.8)
Day 14, 12 hours2.19 (1.14 to 4.21)4.93 (2.26 to 10.8)
SecondaryAUCtau (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)
Reported as:
Geometric mean · ng.hour/mL
AUCtau (PK Part C)
ng.hour/mLPart C Dose 1Part C Dose 2
AM Day 1210 ± 48.3521 ± 59.2
PM Day 1231 ± 92.5540 ± 53.9
AM Day 14254 ± 68.9792 ± 59.0
SecondaryAUClast (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)
Reported as:
Geometric mean · ng.hour/mL
AUClast (PK Part C)
ng.hour/mLPart C Dose 1Part C Dose 2
Day1410 ± 59.01034 ± 47.5
Day 14270 ± 67.8831 ± 59.3
SecondaryAUC72 (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
Reported as:
Geometric mean · ng.hour/mL
AUC72 (PK Part C)
ng.hour/mLPart C Dose 1Part C Dose 2
AUC72 (PK Part C)273 ± 66.9837 ± 58.9
Secondaryt1⁄2 (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)
Reported as:
Mean · Hours
t1⁄2 (PK Part C)
HoursPart C Dose 1Part C Dose 2
Day 11.68 ± 0.3171.63 ± 0.177
Day 145.89 ± 2.829.87 ± 7.35
SecondaryAUCinf (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)
Reported as:
Geometric mean · ng.hour/mL
AUCinf (PK Part C)
ng.hour/mLPart C Dose 1Part C Dose 2
Day 1449 ± 72.31149 ± 52.8
Day 14273 ± 66.9839 ± 58.9
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)
Reported as:
Geometric mean · Percentage of AUC
%AUCextrap (PK Part C)
Percentage of AUCPart C Dose 1Part C Dose 2
Day 11.36 ± 219.50.832 ± 93.4
Day 141.14 ± 85.30.921 ± 63.6
SecondaryTerminal 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)
Reported as:
Mean · /Hour
Terminal Rate Constant (PK Part C)
/HourPart C Dose 1Part C Dose 2
Day 10.424 ± 0.08480.428 ± 0.0428
Day 140.169 ± 0.1480.123 ± 0.0955
SecondaryCLSS/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
Reported as:
Mean · L/hour
CLSS/F (PK Part C)
L/hourPart C Dose 1Part C Dose 2
CLSS/F (PK Part C)139 ± 87.170.2 ± 31.5
SecondaryVZ/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)
Reported as:
Mean · L
VZ/F (PK Part C)
LPart C Dose 1Part C Dose 2
VZ/F (PK Part C)1221 ± 823977 ± 874
SecondaryRac(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)
Reported as:
Mean · ratio
Rac(AUCtau) (PK Part C)
ratioPart C Dose 1Part C Dose 2
Rac(AUCtau) (PK Part C)1.33 ± 0.6791.65 ± 0.840
SecondaryRac(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)
Reported as:
Mean · ratio
Rac(Cmax) (PK Part C)
ratioPart C Dose 1Part C Dose 2
Rac(Cmax) (PK Part C)1.22 ± 0.6731.29 ± 0.559
SecondarySR(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)
Reported as:
Mean · ratio
SR(AUC) (PK Part C)
ratioPart C Dose 1Part C Dose 2
SR(AUC) (PK Part C)0.556 ± 0.2750.733 ± 0.158

Adverse events

Collected over 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). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A Placebo0/12 (0%)0/12 (0%)0/12 (0%)
Part A Dose 10/6 (0%)0/6 (0%)1/6 (16.7%)
Part A Dose 20/6 (0%)0/6 (0%)1/6 (16.7%)
Part A Dose 30/6 (0%)0/6 (0%)4/6 (66.7%)
Part A Dose 40/6 (0%)0/6 (0%)2/6 (33.3%)
Part A Dose 50/6 (0%)0/6 (0%)2/6 (33.3%)
Part A Dose 60/6 (0%)0/6 (0%)1/6 (16.7%)
Part B Dose 1 Fasted0/6 (0%)0/6 (0%)1/6 (16.7%)
Part B Dose 1 Fed0/6 (0%)0/6 (0%)1/6 (16.7%)
Part B Dose 2 Fasted0/5 (0%)0/5 (0%)0/5 (0%)
Part B Dose 2 Fed0/5 (0%)0/5 (0%)2/5 (40%)
Part C Placebo0/4 (0%)0/4 (0%)3/4 (75%)
Part C Dose 10/6 (0%)0/6 (0%)1/6 (16.7%)
Part C Dose 20/6 (0%)0/6 (0%)2/6 (33.3%)
Most frequent other events
Showing 10 of 17
Most frequent other events
EventPart A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6Part B Dose 1 FastedPart B Dose 1 FedPart B Dose 2 FastedPart B Dose 2 FedPart C PlaceboPart C Dose 1Part C Dose 2
MyalgiaMusculoskeletal and connective tissue disorders0/120/60/60/60/60/60/60/60/60/50/51/40/60/6
SomnolenceNervous system disorders0/120/60/61/60/60/60/60/61/60/50/51/40/60/6
Eczema asteatoticSkin and subcutaneous tissue disorders0/120/60/60/60/60/60/60/60/60/50/51/40/60/6
Hepatic enzymes increasedInvestigations0/120/60/60/60/60/60/60/60/60/51/50/40/60/6
Back painMusculoskeletal and connective tissue disorders0/120/60/60/60/60/61/60/60/60/51/50/40/60/6
DiarrhoeaGastrointestinal disorders0/120/60/61/60/60/60/60/60/60/50/50/40/60/6
Gastrooesophageal refluxGastrointestinal disorders0/120/60/61/60/60/60/60/60/60/50/50/40/60/6
ToothacheGastrointestinal disorders0/120/60/60/61/60/60/61/60/60/50/50/40/60/6
FatigueGeneral disorders0/120/60/61/60/61/60/60/60/60/50/50/40/60/6
ContusionInjury, poisoning and procedural complications0/121/60/60/60/60/60/60/60/60/50/50/40/60/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)Part A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6Part B (Both Groups)Part C PlaceboPart C Dose 1Part C Dose 2Total
Mean37.3 ± 14.8339.0 ± 8.4427.8 ± 4.4932.7 ± 12.7734.3 ± 4.1343.0 ± 13.0831.0 ± 9.0841.9 ± 14.3038.5 ± 9.4738.3 ± 12.7531.5 ± 5.8935.9 ± 4.82
Sex: Female, Male
Sex: Female, Male(Participants)Part A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6Part B (Both Groups)Part C PlaceboPart C Dose 1Part C Dose 2Total
Female6302112401222
Male6364554845454
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Part A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6Part B (Both Groups)Part C PlaceboPart C Dose 1Part C Dose 2Total
Hispanic or Latino101010001004
Not Hispanic or Latino116565661236672
Unknown or Not Reported000000000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6Part B (Both Groups)Part C PlaceboPart C Dose 1Part C Dose 2Total
American Indian or Alaska Native000000000000
Asian1010112401112
Native Hawaiian or Other Pacific Islander000000000000
Black or African American2132022010114
White7424432625342
More than one race110000011015
Unknown or Not Reported100010010003
Region of Enrollment
Region of Enrollment(participants)Part A PlaceboPart A Dose 1Part A Dose 2Part A Dose 3Part A Dose 4Part A Dose 5Part A Dose 6Part B (Both Groups)Part C PlaceboPart C Dose 1Part C Dose 2Total
United Kingdom126666661246676
07

Study locations

1 site
  • Hammersmith Medicines Research
    London, United Kingdom
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Dec 11, 2023

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT06118385
Lead sponsor
BenevolentAI Bio
Responsible party
Sponsor
First posted
Nov 7, 2023
Start date
Aug 30, 2023
Primary completion
Mar 14, 2024
Completion
Mar 18, 2024
Results posted
May 7, 2025
Last update
May 7, 2025

Study contacts

Denisa Wilkes
principal investigator · Hammersmith Medicine Research

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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