A Study to Evaluate the Pharmacokinetics Similarity of CBP-201 in Healthy Adult Chinese Subjects

Healthy Adult Subjects Clinical Trial

Official title:

A Randomized, Open-Label, Parallel-Designed, Phase I Clinical Study to Evaluate the Pharmacokinetics Similarity of Single-Dose CBP-201 Injection With Different Dosage Forms and Strengths in Healthy Adult Chinese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05917782
• Other study ID #: CBP-201-CN004
• Status: Completed
• Phase: Phase 1
• Start date: July 18, 2023
• Est. completion date: October 6, 2023

Study information

• Verified date: October 2023
• Source: Suzhou Connect Biopharmaceuticals, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-center, randomized, open-label, single-dose, parallel-designed PK similarity study.

Description:

A total of 324 healthy subjects are planned to be enrolled and randomized into 3 groups at a ratio of 1:1:1, with 108 subjects in each group. They will receive 2 doses of the test drug T1 (CBP-201 injection (pre-filled syringe, 150 mg/1 mL)), 1 dose of the test drug T2 (CBP-201 injection (pre-filled syringe, 300 mg/2 mL)), and 2 doses of the reference drug R (CBP-201 injection (vial, 150 mg/1 mL)), respectively. The study consists of a screening period (Day-28 to Day-2), a baseline period (Day-1), an administration and observation period (Day1 to Day6), and a follow-up period (Day7 to Day57).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• Est. completion date: October 6, 2023
• Est. primary completion date: October 6, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Subjects who are to read, understand, and sign the ICF.

2. Healthy adult male or female subjects aged 18-45 years (inclusive) at screening, with each sex accounting for at least one-third of the overall sample size.

3. Body mass index (BMI) is between 19 and 28 kg/m2 (inclusive). Male subjects weigh = 50 kg, and female subjects weigh = 45 kg.

4. Subjects with partners must agree to take medically accepted effective contraceptive measures (including physical contraception, surgery, abstinence, etc) from signing of the ICF until 90 days after administration.

5. The results of vital sign assessment, physical examination, clinical laboratory tests (hematology, urinalysis, biochemistry, coagulation) and 12-lead ECG at screening or baseline are normal or abnormal but not clinically significant.

6. Subjects who are able to communicate well with the clinical staff and complete the study according to the protocol.

Exclusion Criteria:

1. Subjects who have diseases or conditions with abnormal clinical manifestations, including but not limited to renal, cardiac, hematological, bronchial, pulmonary, vascular, gastrointestinal, allergic, neurological, endocrine and metabolic diseases (diabetes mellitus, thyroid disorder, and adrenal disorder), skeletal disease and immunodeficiency, cancer, and hepatitis, or cirrhosis.

2. Subjects with allergic diseases (such as allergic rhinitis, allergic asthma) at screening, a history of systemic anaphylaxis, or who may be allergic to any component of the test drugs or similar drugs as determined by the investigator.

3. Subjects who have donated blood or have had substantial loss of blood (> 400 mL) within 3 months before administration.

4. Subjects who have been vaccinated with live (attenuated) vaccines within 3 months before administration.

5. Subjects who have participated in clinical studies of other drugs within 3 months before administration.

6. Subjects who have taken any prescription drugs, over-the-counter drugs, vitamin products, Chinese patent medicines, and Chinese herbal medicines within 1 month before administration.

7. Subjects who have been diagnosed with clinically significant diseases or have undergone major surgical procedures within 1 month before administration, or who are scheduled to undergo major surgery during the study.

8. Female subjects who test positive for pregnancy at screening or baseline or who are lactating.

9. Subjects who smoke more than 5 cigarettes or equivalent per day within 3 months before administration.

10. Subjects who have a history of drug abuse within the last 5 years, who have used narcotics within 3 months before administration, or who test positive in urine drug screening at the screening/baseline visit.

11. Subjects who have a history of regular alcohol consumption, which is defined as consumption of more than 7 units of alcohol per week for females or more than 14 units of alcohol per week for males (1 unit of alcohol equals 360 mL of beer, 45 mL of 40% liquor, or 150 mL of wine) within 3 months before administration, who take any alcohol-containing product within 48 h before administration, or who test positive in blood alcohol tests at the screening/ baseline visit.

12. Subjects with known symptoms of dermatitis or skin abnormalities at and around the site of administration.

13. Subjects who test positive for treponema pallidum antibody (TP-Ab), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C virus antibody (HCV-Ab), and human immunodeficiency virus antibody (HIV-Ab).

14. Patients with active tuberculosis, latent tuberculosis, or nontuberculous mycobacterial infection at screening;

Notes:

• Unless treatment records clearly documented by a specialist demonstrate that the patients have been adequately treated and may begin treatment with biological product (based on the medical judgment by the investigator and/or infectious disease specialist);
• If needed, T-spot tests may be used to assist diagnosis of suspected tuberculosis.

15. Subjects with white blood cell count and neutrophil count below the lower limit of normal.

16. Female subjects with hemoglobin values less than 110 g/L or male subjects less than 120 g/L.

17. Subjects who cannot tolerate venous blood sampling, or who have a history of acupuncture syncope or hemophobia.

18. Subjects who still need or plan to engage in strenuous physical activity or exercise during the study.

19. Any other conditions that the investigator determines may affect the subject's provision of informed consent or compliance with the study protocol, or that the investigator deems unsuitable for participation in this study, or the subjects' participation in the study may affect the study results or their own safety.

Related Conditions & MeSH terms

• Healthy Adult Subjects

Intervention

Biological:
• Test drug (T1): CBP-201 injection (pre-filled syringe, 150 mg/1 mL)
subcutaneous injection of 2 doses on Day 1
• Test drug (T2): CBP-201 injection (pre-filled syringe, 300 mg/2 mL)
subcutaneous injection of 1 dose on Day 1
• Reference drug (R): CBP-201 injection (vial, 150 mg/1 mL)
subcutaneous injection of 2 doses on Day 1

Locations

Country	Name	City	State
China	The Second Hospital of Anhui Medical University	Hefei	Anhui

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Connect Biopharmaceuticals, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax: Maximum concentration	Pharmacokinetics similarity evaluation for test drug T1, test drug T2 and reference drug R	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Primary	AUC0-t: Area under the plasma concentration-time curve from the start of administration to the last measurable concentration time point T	Pharmacokinetics similarity evaluation for test drug T1, test drug T2 and reference drug R	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Primary	AUC0-inf: Area under the plasma concentration-time curve from the start of administration to infinity	Pharmacokinetics similarity evaluation for test drug T1, test drug T2 and reference drug R	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Maximum concentration (Cmax)	Calculated by non-compartmental analysis (NCA) using WinNonLin V8.3.1 (or higher version)	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Area under the plasma concentration-time curve from the start of administration to the last measurable concentration time point T (AUC0-t)	Calculated by non-compartmental analysis (NCA) using WinNonLin V8.3.1 (or higher version)	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Area under the plasma concentration-time curve from the start of administration to infinity (AUC0-inf)	Calculated by non-compartmental analysis (NCA) using WinNonLin V8.3.1 (or higher version)	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Time to peak (Tmax)	Calculated by non-compartmental analysis (NCA) using WinNonLin V8.3.1 (or higher version)	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Elimination half-life (t1/2)	Calculated by non-compartmental analysis (NCA) using WinNonLin V8.3.1 (or higher version)	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Apparent clearance (CL/F)	Calculated by non-compartmental analysis (NCA) using WinNonLin V8.3.1 (or higher version)	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Apparent volume of distribution (Vz/F)	Calculated by non-compartmental analysis (NCA) using WinNonLin V8.3.1 (or higher version)	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Terminal elimination phase rate constant (?z)	Calculated by non-compartmental analysis (NCA) using WinNonLin V8.3.1 (or higher version)	Pre-dose and 6hour, 24hour, 48hour, 72hour, 96hour, 120hour, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57 post-dose
Secondary	Adverse events (AEs)	All adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) (the latest version).	Up to 57 days post dosing
Secondary	Injection site reactions	The injection site will be examined and the results will be judged by the investigator.	Day1, Day2, Day3, Day4, Day6, Day8, Day15, Day22, Day29, Day57
Secondary	Blood Pressure (systolic and diastolic blood pressures)	The results as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day1, Day2, Day3, Day4, Day6, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57
Secondary	Pulse	The results as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day1, Day2, Day3, Day4, Day6, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57
Secondary	Body Temperature (ear temperature)	The results as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day1, Day2, Day3, Day4, Day6, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57
Secondary	Respiratory Rate	The results as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day1, Day2, Day3, Day4, Day6, Day8, Day10, Day11, Day12, Day15, Day18, Day22, Day29, Day36, Day43, Day57
Secondary	Physical examination	Physical examination items include: skin (including observation of the planned injection site (abdomen) and surrounding skin during the screening period and at baseline), lymph nodes, head, eyes, neck, chest, abdomen, spine/extremities, and nervous system. The results of physical examination will be evaluated by investigator's observation.	pre-dose, Day6, Day15, Day29, Day57
Secondary	12-lead electrocardiogram (ECG)	ECG variables include ventricular heart rate, PR interval, QRS interval, QT interval, and QTcF interval.	pre-dose, Day1, Day2, Day4, Day6, Day10, Day15, Day22, Day29, Day36, Day43, Day57
Secondary	Clinical laboratory test: Hematology - Hemoglobin (Hgb)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - Hematocrit (Hct)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - red blood cell count (RBC)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - platelet count	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - white blood cell count (WBC)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - lymphocyte count	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - lymphocyte percentage	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - neutrophil count	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - neutrophil percentage	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - monocyte count	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - monocyte percentage	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - eosinophil count	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - eosinophil percentage	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - basophil count	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - basophil percentage	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - mean corpuscular hemoglobin (MCH)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Hematology - mean corpuscular volume (MCV)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Urinalysis	Urine protein, cast, urine red blood cells, urine white blood cells, urine pH, urine ketone body, glucose urine, urine bilirubin, and urine occult blood	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - Glucose (Glu)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - alanine aminotransferase (ALT)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - aspartate aminotransferase (AST)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - alkaline phosphatase (ALP)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - lactate dehydrogenase (LDH)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - gamma-glutamyltransferase (?-GGT)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - serum total protein (TP)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - albumin (ALB)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - total bilirubin (TBIL)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - direct bilirubin (DBIL)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - blood urea nitrogen (BUN)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - creatinine (Crea)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - sodium (Na)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - potassium (K)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - chlorine (Cl)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - calcium (Ca)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - phosphorus (P)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - triglycerides (TG)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - total cholesterol (TC)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - high-density lipoprotein cholesterol (HDL-C)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - low-density lipoprotein cholesterol (LDL-C)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - uric acid (UA)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Biochemistry - creatine kinase (CK)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Coagulation - International normalized ratio (INR)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Coagulation - prothrombin time (PT)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Coagulation - activated partial thromboplastin time (APTT)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Coagulation - fibrinogen (FIB)	The results of clinical laboratory tests, as well as their changes from baseline will be statistically summarized by dose group and visit.	pre-dose, Day6, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Pregnancy test	Blood pregnancy test (for females only)	pre-dose, Day15, Day29, Day43, Day57
Secondary	Clinical laboratory test: Infectious serology	Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, Treponema pallidum antibody, and human immunodeficiency virus antibody	pre-dose
Secondary	Clinical laboratory test: Blood alcohol test	Blood alcohol test	pre-dose
Secondary	Clinical laboratory test: Urine drug abuse screening	Morphine, methamphetamine, ketamine, methylenedioxy methylamphetamine, marijuana, and cocaine	pre-dose
Secondary	T-Spot	If necessary, T-spot screening can be performed for priorly infected or suspected patients	pre-dose
Secondary	Immunogenicity: The positive rate and titer of anti-drug antibody (ADA), and the positive rate of neutralizing antibody (Nab, in case of ADA positive results)	Immunogenicity will be analyzed based on IMS. The number and percentage of subjects positive for CBP-201 ADA and Nab will be summarized by dose group.	pre-dose, Day11, Day29, Day43, Day57