A Randomized, Open-Label, 2-Arm, Parallel Group, Single Dose, Multi-Centre Study in Healthy Male Subjects to Investigate the Comparability of Pharmacokinetics of the Fixed-Dose Combination of Pertuzumab and Trastuzumab Administered Subcutaneously Using a Handheld Syringe or Using the On-Body Delivery System
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 151
- 试验地点
- 5
- 主要终点
- Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Pertuzumab
研究概览
简要总结
This is a randomized, open-label, 2-arm, parallel-group, single-dose, multi-center study in healthy male subjects to investigate the comparability of the pharmacokinetics of the fixed-dose combination of pertuzumab and trastuzumab administered subcutaneously using the proprietary on-body delivery system or a handheld syringe with hypodermic needle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects age 18-45 years at time of signing Informed Consent Form
- •Ability to comply with the study protocol
- •Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, during the treatment period and for 7 months after the dose of PH FDC SC
- •A body mass index (BMI) between 18 and 32 kilograms per metre squared (kg/m2), inclusive
- •Intact normal skin without potentially obscuring tattoos, pigmentation, or lesions in the area for intended injection on the thighs
- •Baseline LVEF≥55% measured by echocardiogram (ECHO)
- •No history of hypersensitivity or confirmed, clinically significant and clinically relevant allergic reactions, either spontaneously or following any drug administration
- •No history of any clinically significant and clinically relevant cardiac condition
- •No history of previous anticancer treatments including pertuzumab, trastuzumab, anthracyclines, or any cardiotoxic drugs
- •No apparent family history of clinically significant and clinically relevant hypersensitivity, allergy, and severe cardiac diseases
- •No contraindications from detailed medical and surgical history and physical examinations
- •No previous enrollment in this study protocol and no concurrent enrollment in any other study protocol
排除标准
- •Positive urine test for drugs of abuse as per local standard (for alcohol abuse, positive breath test is also acceptable)
- •Positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) 1 or 2, showing: History of exposure to HBV, HCV, or HIV; or Active viral hepatitis infection (HBV or HCV) or HIV infection
- •Systolic blood pressure ≥140 millimetres of mercury (mmHg) or <90 mmHg, or diastolic blood pressure >90 mmHg or <50 mmHg
- •Use of prohibited medications including non-prescription medications, nutraceuticals, nutritional supplements or any herbal remedies taken within 10 days or 5 times the elimination half-life (whichever is longer) prior to randomization into the study
- •Concomitant subcutaneous, intravenous, or any parenteral drugs within 90 days prior to screening
- •Participation in an investigational drug or device study within 90 days or five times the elimination half-life (whichever is longer) prior to screening
- •Donation of blood over 500 millilitres (mL) within 3 months prior to enrollment
- •Known severe hypersensitivity to plaster, medical adhesive tapes, or bandages
- •Known allergy to murine proteins, hyaluronidase, bee, or vespid venom, or any other ingredient in the formulation of rHuPH20 (Hylenex® recombinant [hyaluronidase human injection]) or any other ingredients and excipients in the formulation of PH FDC SC
- •Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, CBC, chemistry panel, and urinalysis)
- •Clinically relevant electrocardiogram abnormalities at screening or Day -1
- •History of any cardiac condition
- •Lower extremity edema or pathology (e.g., cellulitis, lymphatic disorder or prior surgery, pre-existing pain syndrome, previous lymph node dissection etc.) that could interfere with any protocol-specified outcome assessment
- •Any history of clinically significant and clinically relevant allergies, oncologic, psychiatric, gastrointestinal, renal, hepatic, cardiovascular or pulmonary disease
- •Concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in this study
- •Any clinically relevant history of systemic disease (e.g., malignancy, diabetes mellitus, gastrointestinal, renal, hepatic, cardiovascular, rheumatological, or pulmonary disease)
- •History of breast cancer or treatment for breast cancer
- •Current chronic daily treatment (continuous for >3 months) with corticosteroids (dose ≥10 mg/day methylprednisolone), excluding inhaled corticosteroids
- •Receipt of intravenous antibiotics for infection within 7 days prior to enrollment into the study
研究组 & 干预措施
Arm 1: PH FDC SC Using a Handheld Syringe
A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the participant's anterior thigh on Day 1, using a handheld syringe with hypodermic needle.
干预措施: Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC) (Drug)
Arm 1: PH FDC SC Using a Handheld Syringe
A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the participant's anterior thigh on Day 1, using a handheld syringe with hypodermic needle.
干预措施: Handheld Syringe with Hypodermic Needle (Device)
Arm 2: PH FDC SC Using the OBDS
A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the participant's anterior thigh on Day 1, using the on-body delivery system (OBDS).
干预措施: Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC) (Drug)
Arm 2: PH FDC SC Using the OBDS
A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the participant's anterior thigh on Day 1, using the on-body delivery system (OBDS).
干预措施: On-Body Delivery System (Device)
结局指标
主要结局
Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Pertuzumab
时间窗: Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63
For the analysis of AUC0-62days, participants in the Per Protocol Pharmacokinetics (PK) Analysis Population (PAP) with missing Day 63 PK pertuzumab concentration data or with a Day 63 PK sample time deviation outside a +/-120-hour window of planned sampling time were excluded. Participants were excluded from the PAP for the following reasons: 1. The participant violates inclusion or exclusion criteria regarding body mass index (BMI), use of prohibited medications and concomitant subcutaneous, intravenous (IV), or any parenteral drugs, participation in an investigational drug or device study, current chronic daily treatment with corticosteroids, and receipt of IV antibiotics for infection. 2. An SC injection site other than thigh is used; 3. Any participant whose injection is not successfully performed.
Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Trastuzumab
时间窗: Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63
For the analysis of AUC0-62days, participants in the Per Protocol Pharmacokinetics (PK) Analysis Population (PAP) with missing Day 63 PK trastuzumab concentration data or with a Day 63 PK sample time deviation outside a +/-120-hour window of planned sampling time were excluded. Participants were excluded from the PAP for the following reasons: 1. The participant violates inclusion or exclusion criteria regarding body mass index (BMI), use of prohibited medications and concomitant subcutaneous, intravenous (IV), or any parenteral drugs, participation in an investigational drug or device study, current chronic daily treatment with corticosteroids, and receipt of IV antibiotics for infection. 2. An SC injection site other than thigh is used; 3. Any participant whose injection is not successfully performed.
Maximum Serum Concentration (Cmax) of Pertuzumab
时间窗: Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63
For analysis of Cmax, participants from the Per Protocol PK Analysis Population (PAP) with two or more missing PK pertuzumab concentration data on any of Days 3, 5, 7, 9 or 11 were excluded. Participants were excluded from the PAP for the following reasons: 1. The participant violates inclusion or exclusion criteria regarding body mass index (BMI), use of prohibited medications and concomitant subcutaneous, intravenous (IV), or any parenteral drugs, participation in an investigational drug or device study, current chronic daily treatment with corticosteroids, and receipt of IV antibiotics for infection. 2. An SC injection site other than thigh is used; 3. Any participant whose injection is not successfully performed.
Maximum Serum Concentration (Cmax) of Trastuzumab
时间窗: Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63
For analysis of Cmax, participants from the Per Protocol PK Analysis Population (PAP) with two or more missing PK trastuzumab concentration data on any of Days 3, 5, 7, 9 or 11 were excluded. Participants were excluded from the PAP for the following reasons: 1. The participant violates inclusion or exclusion criteria regarding body mass index (BMI), use of prohibited medications and concomitant subcutaneous, intravenous (IV), or any parenteral drugs, participation in an investigational drug or device study, current chronic daily treatment with corticosteroids, and receipt of IV antibiotics for infection. 2. An SC injection site other than thigh is used; 3. Any participant whose injection is not successfully performed.
次要结局
- Observed Serum Concentration of Pertuzumab on Day 22(Day 22)
- Observed Serum Concentration of Trastuzumab on Day 22(Day 22)
- Observed Serum Concentration of Pertuzumab on Day 63(Day 63)
- Observed Serum Concentration of Trastuzumab on Day 63(Day 63)
- Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Pertuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Trastuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Observed Time to Maximum Serum Concentration (Tmax) of Pertuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Observed Time to Maximum Serum Concentration (Tmax) of Trastuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Terminal Elimination Half-Life (t1/2) of Pertuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Terminal Elimination Half-Life (t1/2) of Trastuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Apparent Drug Clearance (CL/F) of Pertuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Apparent Drug Clearance (CL/F) of Trastuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Apparent Volume of Distribution (Vd/F) of Pertuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Apparent Volume of Distribution (Vd/F) of Trastuzumab(Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63)
- Summary of the Number of Participants With at Least One Adverse Event, With Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)(From study drug dose until safety follow-up visit (up to 7 months))
- Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time(Baseline, once between Days 20 and 35, and once between Days 56 and 63)
- Change From Baseline Pulse Rate Over Time(Baseline, Days 2, 7, 22, and 63)
- Change From Baseline Respiratory Rate Over Time(Baseline, Days 2, 7, 22, and 63)
- Change From Baseline Systolic Blood Pressure Over Time(Baseline, Days 2, 7, 22, and 63)
- Change From Baseline Diastolic Blood Pressure Over Time(Baseline, Days 2, 7, 22, and 63)
- Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator(At Baseline (predose) and Post-Baseline (postdose Days 2, 7, 22, and 63))
- Number of Participants With Adverse Events Based on Laboratory Test Abnormalities(From Baseline until Day 63)
- Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale(Day 1: pre-dose, during drug injection, after drug injection while removing the device or syringe, and 2 hours after drug injection)
- Number of Participants With Skin Irritation and Sensitization Reactions at the Injection Site, as Reported by Investigators in the Device Monitoring Questionnaire(Prior to injection and after injection on Day 1)
- Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire(Day 1)
- Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device(Day 1)