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

NCT04811469 | Completed Phase 1

• 1 other identifier: CBP-174AU001
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Adult Subjects

Outcome Measures

Primary Outcomes (69)

• 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 Outcomes (9)

• AUC0-72 h: Area under the plasma concentration-time curve of CBP-174 from time 0 to 72h

  Up to 72 hours post dosing

• AUC0-∞: Area under the plasma concentration-time curve of CBP-174 from time 0 to infinity

  Up to 72 hours post dosing

• Cmax: Maximum observed concentration

  Up to 72 hours post dosing

• Tmax: Time to maximum concentration;

  Up to 72 hours post dosing

• T1/2: Elimination half-life;

  Up to 72 hours post dosing

Study Arms (2)

CBP-174

EXPERIMENTAL

CBP-174 oral solution

Drug: CBP-174

Placebo

EXPERIMENTAL

placebo oral solution

Drug: Placebo

Interventions

CBP-174 DRUG

CBP-174 oral solution, given once

CBP-174

Placebo DRUG

Placebo oral solution, given once

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Healthy male and female subjects, aged 18 to 55 years (both inclusive)
• 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
• 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
• 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.
• Subjects who are able to communicate well with Investigators, as well as understand and adhere to the requirements of this study

You may not qualify if:

• 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:
• Subjects who have difficulties in venous blood collection or history of dizziness with blood or needles
• Female subjects who have a positive pregnancy test or are breastfeeding
• 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
• 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
• 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
• Subjects who have a history of significant eye diseases (such as keratitis, and scleritis, etc.) or clinical significant eye signs (conjunctiva hyperemia, etc.)
• Subjects who have a history of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD)
• 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
• 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
• 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

Sponsors & Collaborators

• Connect Biopharma Australia Pty Ltd: lead

Study Sites (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

Location

Study Officials

• Australia Connect

  Connect Biopharma Australia Pty Ltd

  STUDY DIRECTOR

• Suzhou Connect

  Connect Biopharm LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 16, 2020
• First Posted: March 23, 2021
• Study Start: May 24, 2021
• Primary Completion: May 14, 2022
• Study Completion: May 21, 2022
• Last Updated: August 10, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)