Clinical trial NCT05391880: Study of Orally Administered BEBT-503 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: BeBetter Med Inc
Sponsor class: INDUSTRY
First posted: 2022-05-26
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: single dose safety
timeFrame: from baseline to Day10
measure: multiple dose safety
timeFrame: from baseline to Day18
Secondary outcomes:
measure: AUC0-∞ after single dose
timeFrame: Pre-dose to 48 hours postdose
measure: Cmax after single dose
timeFrame: Pre-dose to 48 hours postdose
measure: t1/2 after single dose
timeFrame: Pre-dose to 48 hours postdose
measure: Tmax after single dose
timeFrame: Pre-dose to 48 hours postdose
measure: CL/F after single dose
timeFrame: Pre-dose to 48 hours postdose
measure: Vz/F after single dose
timeFrame: Pre-dose to 48 hours postdose
measure: AUC0-τ after multiple dose
timeFrame: 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
measure: AUC0-∞ after multiple dose
timeFrame: 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
measure: Cmax after multiple dose
timeFrame: 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
measure: t1/2 after multiple dose
timeFrame: 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
measure: Tmax after multiple dose
timeFrame: 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
measure: Cmin after multiple dose
timeFrame: 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
measure: RAAUC0-τ after multiple dose
timeFrame: 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
measure: RACmax after multiple dose
timeFrame: 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
measure: effect of food on the single oral dose AUC0-∞
timeFrame: Pre-dose to 48 hours postdose
measure: effect of food on the single oral dose Cmax
timeFrame: Pre-dose to 48 hours postdose
measure: effect of food on the single oral dose Tmax
timeFrame: Pre-dose to 48 hours postdose
measure: effect of food on the single oral dose t1/2
timeFrame: Pre-dose to 48 hours postdose
measure: effect of food on the single oral dose CL/F
timeFrame: Pre-dose to 48 hours postdose
measure: effect of food on the single oral dose Vz/F
timeFrame: Pre-dose to 48 hours postdose
measure: metabolites of BEBT-503 in urine
timeFrame: Pre-dose to 48 hours postdose
measure: metabolites of BEBT-503 in plasma
timeFrame: Pre-dose to 48 hours postdose
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd
Study officials:
affiliation: Nucleus Network
name: Jason Lickliter, CMO
role: STUDY_DIRECTOR
References: