Study of Orally Administered BEBT-503 in Healthy Subjects

A Randomized, Double-Blind, Placebo-Controlled Study of Orally Administered BEBT-503 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses (SAD) and Multiple Ascending Doses (MAD) in Healthy Subjects

This is a Phase I, randomized, double-blind, placebo-controlled, first-in-human study in which the safety, tolerability, and pharmacokinetic of orally administered BEBT-503 will be assessed in healthy adult subjects.

The study will consist of 2 parts: a SAD phase (Part A) enrolling a total of 5 cohorts of healthy subjects; a MAD phase (Part B) enrolling 2 cohorts of healthy subjects; One cohort of Part A will receive BEBT-503 under both fasted and fed conditions to investigate the effect of food

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: BEBT-503 20mg; Drug: BEBT-503 40mg; Drug: BEBT-503 80mg; Drug: BEBT-503 120mg; Drug: BEBT-503 180mg; Drug: placebo 20mg; Drug: placebo 40mg; Drug: placebo 80mg; Drug: placebo 120mg; Drug: placebo 180mg

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3004
    • Nucleus Network Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Males or females, of any race, between 18 and 55 years of age, inclusive.
2. Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) with a minimum body weight of 50 kg. Participants with a BMI up to 32.0 kg/m2 may be enrolled with the sponsor's approval
3. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia, eg, suspicion of Gilbert's syndrome based on total and direct bilirubin, is not acceptable) at Screening and Check-in as assessed by the Investigator (or designee), as applicable.
4. Resting heart rate ≥ 45 bpm and ≤ 90 bpm with a single 12-lead ECG at Screening.
5. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
6. Male subjects must agree to refrain from sperm donation and females should refrain from ova donation from the date of Check-in (Day-1) until 90 days after the Follow-up visit.
7. Participants have ability to swallow and retain oral medication.
8. Able to comprehend and willing to sign an Information and Consent Form and to abide by the study restrictions.

Exclusion Criteria:

1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
2. History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection.
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
4. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed, but not cholecystectomy).
5. History of malignancy (cured basal cell or squamous cell carcinoma of the skin, ductal carcinoma in situ are eligible).
6. Presence of a malabsorption syndrome possibly affecting drug absorption (eg, Crohn's disease or chronic pancreatitis).

7. Any of the following:

   1. corrected QT interval by Fridericia formula> 450 msec confirmed by repeat measurement.
   2. QRS duration > 120 msec confirmed by repeat measurement.
   3. PR interval > 220 msec confirmed by repeat measurement.
   4. findings which would make corrected QT interval measurements difficult or corrected QT interval data uninterpretable.
   5. history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome).
8. History of alcoholism or drug/chemical abuse within 6 months prior to Check-in.
9. Alcohol consumption of > 21 units per week for males and > 14 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
10. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Check-in.
11. Positive hepatitis panel and/or positive human immunodeficiency virus (HIV) test.
12. Participation in a clinical study involving administration of an investigational agent or vaccine (new chemical entity) or having received a biological product in the past 90 days prior to dosing.
13. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
14. Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
15. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
16. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
17. Use of tobacco- or nicotine-containing products within 1 month prior to Check-in, or positive cotinine at Screening or Check-in.
18. Receipt of blood products within 2 months prior to Check-in and donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
19. Any major surgery within 4 weeks prior to first dosing.
20. Poor peripheral venous access.
21. Have previously completed or withdrawn from this study investigating BEBT-503, and have previously received the investigational product.
22. Subject who, in the opinion of the Investigator (or designee), should not participate in this study.
23. Subject is not willing to minimize or avoid exposure to natural or artificial sunlight (tanning beds or ultraviolet A/B treatment) following administration of study drug until 24 hours after the last dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug:BEBT-503; BEBT-503	Drug: BEBT-503 20mg; BEBT-503 capsule; Drug: BEBT-503 40mg; BEBT-503 capsule; Drug: BEBT-503 80mg; BEBT-503 capsule; Drug: BEBT-503 120mg; BEBT-503 capsule; Drug: BEBT-503 180mg; BEBT-503 capsule
Placebo Comparator: Drug: Placebo; Placebo	Drug: placebo 20mg; placebo capsule; Drug: placebo 40mg; placebo capsule; Drug: placebo 80mg; placebo capsule; Drug: placebo 120mg; placebo capsule; Drug: placebo 180mg; placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
single dose safety	Number of the Adverse Events that are related to the single dose treatment from baseline to Day 10	from baseline to Day10
multiple dose safety	Number of the Adverse Events that are related to the multiple dose treatment from baseline to Day 18	from baseline to Day18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-∞ after single dose	PK characteristics after single dose	Pre-dose to 48 hours postdose
Cmax after single dose	PK characteristics after single dose	Pre-dose to 48 hours postdose
t1/2 after single dose	PK characteristics after single dose	Pre-dose to 48 hours postdose
Tmax after single dose	PK characteristics after single dose	Pre-dose to 48 hours postdose
CL/F after single dose	PK characteristics after single dose	Pre-dose to 48 hours postdose
Vz/F after single dose	PK characteristics after single dose	Pre-dose to 48 hours postdose
AUC0-τ after multiple dose	PK characteristics after multiple dose	Day 1: pre-am dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24hours post-am dose Days 4 to 9: pre-am dose Day 10: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-final dose
AUC0-∞ after multiple dose	PK characteristics after multiple dose	Day 1: pre-am dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24hours post-am dose Days 4 to 9: pre-am dose Day 10: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-final dose
Cmax after multiple dose	PK characteristics after multiple dose	Day 1: pre-am dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24hours post-am dose Days 4 to 9: pre-am dose Day 10: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-final dose
t1/2 after multiple dose	PK characteristics after multiple dose	Day 1: pre-am dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24hours post-am dose Days 4 to 9: pre-am dose Day 10: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-final dose
Tmax after multiple dose	PK characteristics after multiple dose	Day 1: pre-am dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24hours post-am dose Days 4 to 9: pre-am dose Day 10: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-final dose
Cmin after multiple dose	PK characteristics after multiple dose	Day 1: pre-am dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24hours post-am dose Days 4 to 9: pre-am dose Day 10: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-final dose
RAAUC0-τ after multiple dose	PK characteristics after multiple dose	Day 1: pre-am dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24hours post-am dose Days 4 to 9: pre-am dose Day 10: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-final dose
RACmax after multiple dose	PK characteristics after multiple dose	Day 1: pre-am dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24hours post-am dose Days 4 to 9: pre-am dose Day 10: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-final dose
effect of food on the single oral dose AUC0-∞	effect of food on the single oral dose PK	Pre-dose to 48 hours postdose
effect of food on the single oral dose Cmax	effect of food on the single oral dose PK	Pre-dose to 48 hours postdose
effect of food on the single oral dose Tmax	effect of food on the single oral dose PK	Pre-dose to 48 hours postdose
effect of food on the single oral dose t1/2	effect of food on the single oral dose PK	Pre-dose to 48 hours postdose
effect of food on the single oral dose CL/F	effect of food on the single oral dose PK	Pre-dose to 48 hours postdose
effect of food on the single oral dose Vz/F	effect of food on the single oral dose PK	Pre-dose to 48 hours postdose
metabolites of BEBT-503 in urine	metabolites analysis	Pre-dose to 48 hours postdose
metabolites of BEBT-503 in plasma	metabolites analysis	Pre-dose to 48 hours postdose

Collaborators and Investigators

• Sponsor: BeBetter Med Inc
• Investigators: Study Director: Jason Lickliter, CMO, Nucleus Network

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Actual): May 29, 2023
• Study Completion (Actual): July 5, 2023

Study Registration Dates

• First Submitted: May 12, 2022
• First Submitted That Met QC Criteria: May 22, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: GBMT-503-P01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No