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

NCT06118385 | Completed Phase 1 Results

• 1 other identifier: BB-8744-1001
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteer Study

Outcome Measures

Primary Outcomes (16)

• 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.

  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

Secondary Outcomes (28)

• Cmax (PK Part A)

  Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

• Tmax (PK Part A)

  Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

• AUC24 (PK Part A)

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

• AUC72 (PK Part A)

  Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

• AUClast (PK Part A)

  Plasma concentrations measured predose on Day 1 and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Study Arms (14)

Part A Dose 1

EXPERIMENTAL

Part A Dose 1 Single dose of 2 mg BEN8744

Drug: BEN8744

Part A Dose 2

EXPERIMENTAL

Part A Dose 2 Single dose of 6 mg BEN8744

Drug: BEN8744

Part A Dose 3

EXPERIMENTAL

Part A Dose 3 Single dose of 20 mg BEN8744

Drug: BEN8744

Part A Dose 4

EXPERIMENTAL

Part A Dose 4 Single dose of 60 mg BEN8744

Drug: BEN8744

Part A Dose 5

EXPERIMENTAL

Part A Dose 5 Single dose of 100 mg BEN8744

Drug: BEN8744

Part A Dose 6

EXPERIMENTAL

Part A Dose 6 Single dose of 120 mg BEN8744

Drug: BEN8744

Part A placebo

EXPERIMENTAL

Part A placebo Single dose of placebo

Drug: Matching Placebo

Part B Dose 1 fed

EXPERIMENTAL

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

Drug: BEN8744

Part B Dose 1 Fasted

EXPERIMENTAL

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

Drug: BEN8744

Part B Dose 2 Fed

EXPERIMENTAL

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

Drug: BEN8744

Part B Dose 2 Fasted

EXPERIMENTAL

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

Drug: BEN8744

Part C Dose 1

EXPERIMENTAL

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

Drug: BEN8744

Part C Dose 2

EXPERIMENTAL

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

Drug: BEN8744

Part C placebo

EXPERIMENTAL

Part C placebo 14 daily doses of placebo

Drug: Matching Placebo

Interventions

BEN8744 DRUG

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

Part A Dose 1; Part A Dose 2; Part A Dose 3; Part A Dose 4; Part A Dose 5; Part A Dose 6; Part B Dose 1 Fasted; Part B Dose 1 fed; Part B Dose 2 Fasted; Part B Dose 2 Fed; Part C Dose 1; Part C Dose 2

Matching Placebo DRUG

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

Part A placebo; Part C placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• BenevolentAI Bio: lead

Study Sites (1)

Hammersmith Medicines Research

London, United Kingdom

Location

Results Point of Contact

• Title: Judit Molnar, MD, PhD
• Organization: Benevolent

judit.molnar.md@benevolent.ai

+44 20 3781 9360

Study Officials

• Denisa Wilkes

  Hammersmith Medicine Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: November 7, 2023
• Study Start: August 30, 2023
• Primary Completion: March 14, 2024
• Study Completion: March 18, 2024
• Last Updated: May 7, 2025
• Results First Posted: May 7, 2025

Record last verified: 2025-04

Locations

GB (1)