A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered BW-40202 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Vital signs (heart rate, beats per minute) changes from Baseline values to Day 169 post dose will be summarized in the table by treatment group.
研究概览
简要总结
This study will test the safety of a new drug called BW-40202 in healthy adults. The drug is a clear liquid given as an injection under the skin (subcutaneous injection). The study will test five different doses of BW-40202 compared to a placebo (saltwater solution).
Participants will be divided into five groups, with each group receiving a different dose of BW-40202 or placebo. In each group, eight people will be randomly assigned to receive either the drug (6 people) or placebo (2 people).
The Safety Review Committee will review the safety data before increasing the dose for the next group.
Study nurses or trained staff will give the injections. Pharmacy staff will keep records of how much drug each participant receives, any returned or destroyed doses, and any changes from the planned dosing schedule. These records will be securely stored and available for review.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm1: Single dose of BW-40202
6 out of 8 participants randomized to cohort 1 will receive BW-40202
干预措施: BW-40202 injection (Drug)
Arm2: Single dose of BW-40202
If deemed safe and tolerable by Safety Review Committee, dose level will escalate to cohort , 6 out of 8 participants within cohort 2 will be randomized to receive BW-40202
干预措施: BW-40202 injection (Drug)
Arm3: Single dose of BW-40202
If deemed safe and tolerable by Safety Review Committee, dose level will escalate to cohort 3, 6 out of 8 participants within cohort 3 will be randomized to receive BW-40202
干预措施: BW-40202 injection (Drug)
Arm4: Single dose of BW-40202
If deemed safe and tolerable by Safety Review Committee, dose level will escalate to cohort 4, 6 out of 8 participants within cohort 4 will be randomized to receive BW-40202
干预措施: BW-40202 injection (Drug)
Arm5: Single dose of BW-40202
If deemed safe and tolerable by Safety Review Committee, dose level will escalate to cohort 5, 6 out of 8 participants within cohort 5 will be randomized to receive BW-40202
干预措施: BW-40202 injection (Drug)
Arm 6: Placebo
There will be 2 participants within each cohort be randomized to receive placebo.
干预措施: Sodium Chloride (Other)
结局指标
主要结局
Vital signs (heart rate, beats per minute) changes from Baseline values to Day 169 post dose will be summarized in the table by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
Abnormal physical examination findings will be listed.
Vital signs (temperature,degrees Celsius) changes from Baseline values to Day 169 post dose will be summarized in the table by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
Abnormal physical examination findings will be listed.
Proportion of participants experiencing at least one treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) from baseline to Day 169. To determine the incidenc of TEAEs and SAEs.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
Incidence of TEAEs (%) = (number of subjects with TEAEs/Total number of subjects) \*100 Incidence of SAEs (%) = (number of subjects with SAEs/total number of subjects)\*100
Collecting the adverse events(AEs) up to D169 and the AEs will be categorized based on Medical Dictionary for Regulatory Activities (MedDRA) terms and clssified by System Organ Class (SOC) and Preferred Term (PT) for summary.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
Adverse events (AEs) were coded using the latest MedDRA version available at the time of study commencement. All AEs were collected after drug administration and were considered TEAEs to be included in the summaries. Summary tables included the number of subjects (%) experiencing an event and the number of events. Subjects who experienced multiple AEs were only counted once in each category (system organ class \[SOC\] and preferred term \[PT\]), but all events were included in the event frequencies (categorical descriptive analysis). The TEAE summaries included: * Overall summary of TEAEs. * TEAE summary by SOC and PT. * TEAE summary of serious events by SOC and PT. * TEAE summary of study-drug related events by SOC and PT. TEAE summary by SOC, PT, and Toxicity Grading. * TEAE summary by SOC, PT, and relationship to study drug. * TEAE summary of events leading to study discontinuation by SOC and PT. * TEAE summary of Injection Site reactions.
Grading the TEAE and SAE based on severity and number of TEAEs and SAEs will be listed based on severity from baseline to Day 169.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
Adverse events are graded based on severity: Mild (Grade 1): No significant impact on daily activities Moderate (Grade 2): Some interference with daily activities Severe (Grade 3): Significant impact on function Life-threatening (Grade 4): Immediate risk of death Fatal (Grade 5): Resulted in death. Severity distribution = (number of subjects with grade X TEAE/total TEAE cases) \*100
Hematology results (concentration of Hemoglobin, g/L; Platelets, 10^9/L; Red blood cell count, 10^12/L) at each time point, including changes from baseline to Day 169 post dose will be summarized by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline. The values that are below the lower limit or above the upper limit of the reference range will be flagged for safety. Those values or changes in values that are identified as being clinically significant will be flagged.
Coagulation results (Activated partial thermoplastic time, s; Prothrombin time, s) at each time point, including changes from baseline to Day 169 post dose will be summarized by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline. The values that are below the lower limit or above the upper limit of the reference range will be flagged for safety. Those values or changes in values that are identified as being clinically significant will be flagged.
Chemistry results (concentration of Albumin, g/L; Alkaline Phosphatase, U/L; Alanine Amintransferase, U/L; Aspartate Aminotransferase, U/L;Direct Billirubin umol/L) at each time point from baseline to Day 169 will be summarized by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline. The values that are below the lower limit or above the upper limit of the reference range will be flagged for safety. Those values or changes in values that are identified as being clinically significant will be flagged.
Urinalysis results（Epithelial cells, crystals, casts, bilirubin) at each time point, including change from baseline to Day 169 post dose will be summarized in the table by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline. The values that are below the lower limit or above the upper limit of the reference range will be flagged for safety. Those values or changes in values that are identified as being clinically significant will be flagged.
Vital signs (blood pressures, millimeters of mercury) changes from Baseline values to Day 169 post dose will be summarized in the table by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
Abnormal physical examination findings will be listed.
Vital signs (respiratory rate, times per minute) changes from Baseline values to Day 169 post dose will be summarized in the table by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
Abnormal physical examination findings will be listed.
Hematology results (White blood cell count and differential (absolute and % differential)) at each time point, including changes from baseline to Day 169 post dose will be summarized by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline. The values that are below the lower limit or above the upper limit of the reference range will be flagged for safety. Those values or changes in values that are identified as being clinically significant will be flagged.
Chemistry results (concentration of Calcium, mmol/L; creatine kinase, U/L; chloride, mmol/L; Gamma Glutamyl Transferase, U/L) at each time point from baseline to Day 169 will be summarized by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline. The values that are below the lower limit or above the upper limit of the reference range will be flagged for safety. Those values or changes in values that are identified as being clinically significant will be flagged.
Changes in ECG (Mean heart rate, bpm; PR Interval,msec; QRS Duration, msec; QT interval, msec; RR interval, msec; QTcF Interval, msec; ) from Baseline to Day 169 post-dose will be summarized.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
12-lead ECGs will be summarized by visit and by treatment group, along with the changes from baseline.The summary of overall interpretation findings table presented counts and percentages for the reported results at Baseline and Day 169/time point. Result categories were ordered as 'Normal', 'Abnormal Not Clinically Significant (NCS)' and 'Abnormal Clinically Significant (CS)' (categorical descriptive analysis).
By subject data listings will be created for all physical examination parameters(general appearance, head, neck, skin and others) from baseline to Day 169 post dose..
时间窗: From first participant enrolled until Day 169 post-dose of last participant
Abnormal physical examination findings will be listed.
Coagulation results (International normalized ratio) at each time point, including changes from baseline to Day 169 post dose will be summarized by treatment group.
时间窗: From first participant enrolled until Day 169 post-dose of last participant
The safety laboratory data will be summarized by visit and by treatment group, along with changes from baseline. The values that are below the lower limit or above the upper limit of the reference range will be flagged for safety. Those values or changes in values that are identified as being clinically significant will be flagged.
次要结局
- maximum plasma concentration data (Cmax, ng/mL) of BW-40202 will be collected for all cohorts at the scheduled PK sampling timepoints.(From first patient enrolled until Day 8 post-dose of last patient.)
- Time to Maximum plasma concentration (Tmax, hr) of BW-40202 will be calculated (hr). T max(Time to Maximum Concentration) is the time at which the maximum observed plasma drug concentration ( Cmax) occurs after drug administration.(From first patient enrolled until Day 8 post-dose of last patient.)
- Calculate the Area Under the Plasma Concentration-Time Curve (AUC, hr*ng/mL), to estimate the AUC beyond the last observed time point (AUC0-∞), the AUC from 0 to 24 hours and AUC from 0 to 48 hours. The AUC represents the total drug exposure over time.(From first patient enrolled until Day 8 post-dose of last patient.)
- Calculate the time required for the plama concentration of a drug to decrease by 50% in the elimination phase. Which is called terminal elimination half-life (t1/2, hr)(From first patient enrolled until Day 8 post-dose of last patient)
- Calculate the Urine output (Aet, mg), Aet (total amount of drug excreted in urine during each time interval)(From first participant being enrolled until 24 hours post-dose of last enrolled participant)
- Calculate the Urine output (Clr, L/h), the renal clearance measures the efficiency of drug elimination by the kidneys.(From first participant being enrolled until 24 hours post-dose of last enrolled participant)