Safety, Tolerability and Pharmacokinetics of CBP-174 in Healthy Adults

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of CBP-174 After Oral Administration

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of CBP-174 after a single oral dose in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: CBP-174; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled, single ascending dose study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of CBP-174 compared to placebo. The study plans to set 6 dose escalation cohorts with single oral dose. Each subject will receive only one dose regimen in this study and the total duration to participate the study is approximately 1 to 4-week.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subjects will be enrolled into the study only if they meet ALL of the following inclusion criteria:

1. Subjects are fully informed of the study, and are willing to participate in the study and sign the informed consent document prior to any procedure
2. Healthy male and female subjects, aged 18 to 55 years (both inclusive)
3. Body mass index is between 18 and 32 kg/m2 (both inclusive), the weight of male subjects ≥ 50 kg, the weight of female subjects ≥ 45 kg
4. Considered generally normal or abnormal with no clinical significance upon medical history, physical examination, vital signs, ECG, and clinical laboratory tests, as judged by the Investigator
5. Female subjects of child-bearing potential must agree to use highly effective contraceptive methods 1 month before the screening, during the entire study, and within 3 months after the end of this study, and have no egg donation plan within 3 months of study end. The male partner of a female subject must agree to use condoms during the screening, entire study, and within 3 months after the end of this study. Male subjects considered fertile must agree to not plan to father a child, donate sperm, and take effective contraceptive methods during the screening, entire study, and within 3 months after the end of this study. The female partner of male subjects must agree to use a highly effective method of female contraception (Section 9.8.3.2) during the screening, entire study, and within 3 months after the end of this study. Contraceptive requirements applies to subjects in same sex relationships for male and female subjects, female subjects of non child bearing potential or male subjects with female partners of non-childbearing potential.
6. Subjects who are able to communicate well with Investigators, as well as understand and adhere to the requirements of this study

Exclusion Criteria:

Subjects will be excluded from the study, if they meet ANY of the following criteria:

Subjects will be excluded from the study, if they meet ANY of the following criteria:

1. Subjects who have difficulties in venous blood collection or history of dizziness with blood or needles
2. Female subjects who have a positive pregnancy test or are breastfeeding
3. Subjects who have allergy/hypersensitivity history to any excipient of CBP-174 solution, or hypersensitivity to antihistamines, or severe allergies at the discretion of Investigator
4. Exposure to any other investigational medicinal product or any other clinical trial within 30 days or 5 times half-lives (whichever is longer) before dosing current study medication
5. Subjects who have a history of gastrointestinal (such as duodenal ulcer, alimentary tract hemorrhage, etc.), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
6. Subjects who have a history of significant eye diseases (such as keratitis, and scleritis, etc.) or clinical significant eye signs (conjunctiva hyperemia, etc.)
7. Subjects who have a history of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD)

8. Subjects who have a history of sleep disorders within 2 years before the screening visit or score highly on the PSQI or ISI questionaire; or have a history of epilepsy or other seizure disorder

   *Pittsburgh Sleep Quality Index (PSQI) ≥ 8 or Insomnia Severity Index (ISI) ≥ 8

9. Subjects who have the medical history of other significant diseases (including but not limited to pulmonary, cardiovascular, gastrointestinal, hematological endocrinological, immunological, dermatological, malignant diseases, mental and nervous systems, and other related diseases) or any other disease/ailment at the discretion of the Investigator

10. Subjects with any of the following clinical laboratory tests results at screening:

    a Aspartate aminotransferase (AST) > 1.5 × the upper limit of normal (ULN)

    b Alanine aminotransferase (ALT) > 1.5 × ULN

    c Serum creatinine > 1.2 × ULN; or creatinine clearance < 60 mL/min (calculated by the Cockcroft-Gault)

    *The clinical laboratory tests of hematology, blood biochemistry, or urinalysis could be allowed repeat once if Investigator considers it necessary

11. Subjects whose QTcF interval prolongation at screening (male: QTcF interval ≥ 450 ms, female: QTcF interval ≥ 470 ms)
12. Blood donation or blood loss more than 400 mL within 3 months before the screening visit
13. Subjects with a known history of drug abuse within 2 years before the screening visit; or positive drug abuse at screening
14. Weekly alcohol consumption of more than 14 units of alcohol (1 unit of alcohol = 360 mL of beer or 45 mL of spirit with the alcohol content of 40% or 150 mL of wine) in any week within the past 3 months before the screening visit; or intake of alcohol-containing products within 48 hours before the first dose, or cannot abstain from any alcohol product during the study, or positive breath alcohol test at screening or check-in (Day -1）
15. Smoking history (> 5 cigarettes per day) within 3 months before the screening visit, or cannot abstain from any tobacco products during the study, or positive urine nicotine test before randomization
16. Excessive drinking of tea, coffee, or caffeine-containing beverage (at least 8 cups per day, 1 cup = 250 mL) any day within 3 months before screening; intake of rich caffeine- or xanthine-containing food or drinks that may produce caffeine or xanthine after being metabolized (eg, coffee, tea, chocolate, cola drinks) within 48 hours before the first dose
17. Any marketed medication (prescription and nonprescription drugs) within 14 days before the first dose or within 5 times the elimination half-life or pharmacodynamic half-life of the medication (excluding oral contraceptives and low dose paracetamol at the discretion of the Investigator, or topical ointments at the discretion of the Investigator)
18. Administration of a Coronavirus Disease 2019 (COVID-19) vaccine in the past 14 days prior to dosing
19. Use of herbal medicines, dietary supplements and vitamin within 14 days before the first dose(permissible at the discretion of the Investigator)
20. Subjects who have a major surgery within 3 months before the first dose or who plan to undergo surgery during the study
21. Positive screening test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody
22. Subjects who are determined as not eligible to participate in this study by the Investigator

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: CBP-174; CBP-174 oral solution	Drug: CBP-174; CBP-174 oral solution, given once
Experimental: Placebo; placebo oral solution	Drug: Placebo; Placebo oral solution, given once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events and serious adverse events	Adverse events will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary.	Up to 7 days post dosing
Severity of adverse events and serious adverse events	The investigator may use the CTCAE V5.0 to assist in the determination of severity and clinical significance.	Up to 7 days post dosing
Change in blood pressure	Blood pressure measured in mmHg	Up to 7 days post dosing
Change in pulse rate	Pulse rate measured per minute	Up to 7 days post dosing
Change in respiratory rate	respiratory rate measured in breaths per minute	Up to 7 days post dosing
Change in tympanic temperature	tympanic temperature measured in celsius	Up to 7 days post dosing
Clinically significant abnormality in physical examinations	Physical examinations includes examination in cutaneous, lymph node, head (especially of eyes) and neck, chest, abdomen, musculoskeletal and nervous systems.	Up to 7 days post dosing
Clinically significant change in heart rate	Heart rate in beats per minute (Bpm) through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.	Up to 7 days post dosing
Clinically significant change in RR interval	R-R interval measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.	Up to 7 days post dosing
Clinically significant change in PR interval	P-R interval measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.	Up to 7 days post dosing
Clinically significant change in QRS complex	QRS complex measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.	Up to 7 days post dosing
Clinically significant change in QT interval	QT interval measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.	Up to 7 days post dosing
Clinically significant change in Fridericia's Correction QT (QTcF) interval	QTcF interval measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Total Protein (TB)	Measured in g/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Albumin (ALB)	Measured in g/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Alanine aminotransferase (ALT)	Measured in IU/L. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Aspartate aminotransferase (AST)	Measured in IU/L. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Alkaline phosphatase (ALP/AKP)	Measured in IU/L. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Glutamyl transpeptidase	Measured in U/L. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Total bilirubin	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Direct Bilirubin	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Indirect Bilirubin	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Glucose	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Urea	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Uric Acid	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Creatinine	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Creatine Kinase	Measured in IU/L. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Potassium	Measured in mmol/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Sodium	Measured in mmol/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Chloride	Measured in mmol/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Calcium	Measured in mmol/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Total Cholesterol	Measured in mmol/L. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal laboratory value in Blood Triglycerides	Measured in mmol/L. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Leukocyte Count	Counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Neutrophil count	Counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Lymphocyte count	Counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Monocytes count	Counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Eosinophils count	Counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Basophil count	Counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in percentage of Neutrophil	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in percentage of Lymphocyte	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in percentage of Monocytes	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in percentage of Eosinophils	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in percentage of Basophils	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Erythrocyte count	Counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Hemoglobin	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Hematocrit	Measured in %. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Platelets	Counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal finding in Urine Occult Blood	Urine Occult Blood will be record as positive or negative. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urine Bilirubin	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urine pH	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urine Protein	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urine Glucose	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urine Specific gravity	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urine Ketones	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urobilinogen	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urinary leukocyte	Urinary leukocyte will be counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urine erythrocytes	Urine erythrocytes will be counted in K/uL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Urine Nitrites	Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Prothrombin time (PT)	Measured in seconds by coagulation tests. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Activated partial thromboplastin time (APTT)	Measured in seconds by coagulation tests. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in International normalized ratio (INR)	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Fibrinogen (FIB)	Measured in mmol/L. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal change in Thrombin time (TT)	Measured in seconds by coagulation tests. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal in Feces colour	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal in Feces properties	The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal in Fecal Red blood cell	Measured in Units. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal in Fecal White blood cell	Measured in Units. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing
Clinically significant abnormal in Fecal Occult blood	Recorded as positive or negative. The physician will judge whether an abnormality is clinically significant.	Up to 7 days post dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-72 h: Area under the plasma concentration-time curve of CBP-174 from time 0 to 72h	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing
AUC0-∞: Area under the plasma concentration-time curve of CBP-174 from time 0 to infinity	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing
Cmax: Maximum observed concentration	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing
Tmax: Time to maximum concentration;	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing
T1/2: Elimination half-life;	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing
λz: Terminal phase rate constant;	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing
CL/F: Apparent clearance;	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing
V/F: Apparent Volume;	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing
%AUCex: Percentage of AUC0-∞ obtained by extrapolation	Calculated by non-compartmental analysis with WinNonlin (Version 8.3.1 or above)	Up to 72 hours post dosing

Collaborators and Investigators

• Sponsor: Connect Biopharma Australia Pty Ltd
• Investigators: Study Director: Australia Connect, Connect Biopharma Australia Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Actual): May 14, 2022
• Study Completion (Actual): May 21, 2022

Study Registration Dates

• First Submitted: August 16, 2020
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 9, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: CBP-174AU001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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