Study of Safety, Tolerability, and Pharmacokinetics of ADB116 for Injection in Healthy Chinese Adults: A Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Phase I Clinical Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Frequency of Treatment-emergent Adverse Events (TEAEs) following a single dose of ADB116 for injection
Study Overview
Brief Summary
A Phase I Study of ADB116 for Injection in Healthy Chinese Adults. This study aims as follows:
Primary Objective:
• To evaluate the safety and tolerability of a single intravenous bolus dose of ADB116 for injection in healthy Chinese adults.
Secondary Objective:
• To evaluate the pharmacokinetic (PK) profile of a single intravenous bolus dose of ADB116 for injection.
Detailed Description
This trial is a single-center, randomized, double-blind, placebo-controlled, single-ascending-dose Phase I clinical trial conducted in healthy Chinese adults to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of a single intravenous bolus dose of ADB116 for injection in healthy Chinese adults.
A total of 34 healthy adults will be enrolled across 6 dose cohorts. For Cohort 1, ADB116 0.03 mg/kg (starting dose) will be administered as a single intravenous injection. Following safety and tolerability assessment, if the dose escalation stopping criteria are not met, the dose will be escalated sequentially using a modified Fibonacci method to Cohorts 2-6: 0.06, 0.09, 0.12, 0.18, and 0.24 mg/kg. After each dose level has been observed through the end of Day 3 (D3), and upon assessment by the sponsor and investigator confirming no safety concerns, the next dose cohort may proceed.
The study consists of three periods: a screening period (up to 28 days, D-28 to D-1), a treatment period (D1), and a follow-up period (D2 to D8). On the dosing day, a single intravenous bolus dose of ADB116 or placebo will be administered.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Voluntarily sign the informed consent form (ICF) prior to any study procedures and be able to comply with the protocol requirements.
- •Aged between 18 and 45 years (inclusive of 18 years up to but not including 46 years) at the time of signing the ICF, male or female.
- •At screening, male subjects must weigh ≥50.0 kg, female subjects must weigh ≥45.0 kg, and body mass index (BMI) = weight (kg) / height² (m²) must be within the range of 19.0-26.0 kg/m² (inclusive).
- •No history of major medical or surgical diseases prior to screening, and results of vital signs, physical examination, 12-lead ECG, laboratory tests, fundoscopic examination, chest X-ray, and abdominal ultrasound during the screening period must be normal or, if slightly outside the normal reference range, considered clinically insignificant by the investigator.
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort 1: ADB116 0.03 mg/kg
ADB116 for Injection 0.03mg/kg, single intravenous bolus injection
Intervention: ADB116 for Injection (Drug)
Cohort 2: ADB116 0.06 mg/kg
ADB116 for Injection 0.06mg/kg, single intravenous bolus injection
Intervention: ADB116 for Injection (Drug)
Cohort 2: ADB116 0.06 mg/kg
ADB116 for Injection 0.06mg/kg, single intravenous bolus injection
Intervention: Placebo for ADB116 for Injection (Drug)
Cohort 4: ADB116 0.12mg/kg
ADB116 for Injection 0.12mg/kg, single intravenous bolus injection
Intervention: ADB116 for Injection (Drug)
Cohort 4: ADB116 0.12mg/kg
ADB116 for Injection 0.12mg/kg, single intravenous bolus injection
Intervention: Placebo for ADB116 for Injection (Drug)
Cohort 5: ADB116 0.18mg/kg
ADB116 for Injection 0.18mg/kg, single intravenous bolus injection
Intervention: ADB116 for Injection (Drug)
Cohort 5: ADB116 0.18mg/kg
ADB116 for Injection 0.18mg/kg, single intravenous bolus injection
Intervention: Placebo for ADB116 for Injection (Drug)
Cohort 6: ADB116 0.24 mg/kg
ADB116 for Injection 0.24 mg/kg， single intravenous bolus injection
Intervention: ADB116 for Injection (Drug)
Cohort 6: ADB116 0.24 mg/kg
ADB116 for Injection 0.24 mg/kg， single intravenous bolus injection
Intervention: Placebo for ADB116 for Injection (Drug)
Cohort 3: ADB116 0.09 mg/kg
ADB116 for Injection 0.09mg/kg, single intravenous bolus injection
Intervention: ADB116 for Injection (Drug)
Cohort 3: ADB116 0.09 mg/kg
ADB116 for Injection 0.09mg/kg, single intravenous bolus injection
Intervention: Placebo for ADB116 for Injection (Drug)
Outcomes
Primary Outcomes
Frequency of Treatment-emergent Adverse Events (TEAEs) following a single dose of ADB116 for injection
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
Safety and tolerability assessed by the frequency, relationship to treatment, severity (using CTCAE criteria, if applicable), seriousness, and expectedness of TEAEs, including adverse drug reactions (ADRs), Grade ≥3 AEs, serious adverse events (SAEs), serious adverse drug reactions (SADRs), AEs leading to treatment interruption, and AEs leading to premature study withdrawal.
Pharmacokinetic (PK) parameters：Cmax
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
Cmax is defined as the highest concentration of the drug reached in the body (usually in plasma, whole blood, or serum) after administration.
Pharmacokinetic (PK) parameters： AUC0-t
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
Area under the plasma concentration-time curve from time zero to the last measurable concentration
Pharmacokinetic (PK) parameters： AUC0-∞
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Pharmacokinetic (PK) parameters：t1/2
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
The time required for the concentration of a drug in the body (typically in plasma) to decrease by one-half.
Pharmacokinetic (PK) parameters：Vz/F
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
The theoretical volume in which the total amount would need to be uniformly distributed to produce the observed plasma concentration
Pharmacokinetic (PK) parameters：CL/F
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
The apparent volume of plasma from which the drug is completely removed per unit time, adjusted for bioavailability (F). It reflects the efficiency of drug elimination following extravascular administration.
Pharmacokinetic (PK) parameters：λz
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
Terminal elimination rate constant
Pharmacokinetic (PK) parameters：percentage of AUC extrapolated (AUC_%Extrap)
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
Percentage of AUCinf due to extrapolation from Tlast to infinity
Pharmacokinetic (PK) parameters： MRT0-t
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
Mean residence time from time zero to the last measurable concentration
Pharmacokinetic (PK) parameters： MRT0-∞
Time Frame: From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose)
Mean residence time from time zero extrapolated to infinity
Secondary Outcomes
- Electrocardiogram (ECG): PR interval(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Coagulation function parameters：thrombin time (TT)(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Coagulation function parameters：activated partial thromboplastin time (APTT)(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Coagulation function parameters：prothrombin time (PT)(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Coagulation function parameters：fibrinogen (FIB)(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Coagulation function parameters：fibrin/fibrinogen degradation products (FDP)(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Coagulation function parameters：plasma D-dimer(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Injection site reactions(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Electrocardiogram (ECG): heart rate(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Electrocardiogram (ECG): QRS duration(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Electrocardiogram (ECG): QTc interval(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Vital sign: Sitting blood pressure (systolic and diastolic)(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Vital sign: pulse(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Vital sign: temperature(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination:skin(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination: general appearance(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination:head(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination:eyes(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination: ears(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination:oral(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination:throat(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination:neck(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination:heart(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination:lungs(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination: extremities(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination: neuromuscular(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Physical examination: abdomen(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Clinical laboratory tests: hematology(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Clinical laboratory tests: urinalysis(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Clinical laboratory tests: fecal occult blood(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))
- Clinical laboratory tests: blood chemistry(From the date of first study drug administration to the End of Study visit (defined as 8 days after last dose))