Healthy Male Subjects
Conditions
Brief summary
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.
Interventions
DRUGFixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC)
A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the anterior thigh, using either a handheld syringe with hypodermic needle (Arm 1) or the on-body delivery system (Arm 2).
DEVICEHandheld Syringe with Hypodermic Needle
A single 10-mL dose of PH FDC SC will be administered as a subcutaneous (SC) injection using a handheld manual syringe.
DEVICEOn-Body Delivery System
A single 10-mL dose of PH FDC SC will be administered as a subcutaneous (SC) injection using the on-body delivery system (OBDS).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | The adverse event (AE) severity grading scale NCI CTCAE v5.0 was used for assessing AE severity. Any AEs for which the NCI CTCAE v5.0 did not provide a grading scale, the standard four-point scale from 1 to 4 (mild, moderate, severe, life-threatening) was used. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade. AEs to monitor included administration-related reactions, hypersensitivity and anaphylaxis, diarrhoea, rash, cardiac dysfunction, neutropenia or febrile neutropenia, mucositis, and interstitial lung disease. |
| Observed Serum Concentration of Pertuzumab on Day 22 | Day 22 | — |
| Change From Baseline Pulse Rate Over Time | Baseline, Days 2, 7, 22, and 63 | Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements. |
| Change From Baseline Respiratory Rate Over Time | Baseline, Days 2, 7, 22, and 63 | Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements. |
| Change From Baseline Systolic Blood Pressure Over Time | Baseline, Days 2, 7, 22, and 63 | Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements. |
| Change From Baseline Diastolic Blood Pressure Over Time | Baseline, Days 2, 7, 22, and 63 | Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements. |
| 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) | For safety monitoring purposes, the investigator was required to review, sign, and date all electrocardiogram (ECG) reports. Any morphologic waveform changes or other ECG abnormalities were documented by the investigator. Post-baseline, if all examinations were normal, then it was categorized as 'Normal'. If any abnormality was reported, then it was categorized as 'Abnormal'. 'Clinically significant' is a subset of the abnormal category. |
| Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | From Baseline until Day 63 | Not every laboratory abnormality qualified as an adverse event. A laboratory test result had to be reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; was clinically significant in the investigator's judgment. |
| 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 | Pain intensity scores were assessed by the participants using the Visual Analog Scale (VAS) on a line measuring between 0 mm ('no pain') and 100 mm ('unbearable pain'). The VAS was completed in both study arms to assess the level of pain experienced by the participant in relation to the injection of Phesgo. On Day 1, pain assessments were performed prior to, during, and immediately after injection of Phesgo when the needle or device was removed, and 2 hours after 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 | Skin irritation and sensitization reactions at the site of injection caused by the adhesion of the OBDS to the skin were assessed by the study staff using the device monitoring questionnaire in the eCRF. Dermal effects were reported on a scale from 0 (no evidence or irritation) to 7 (strong reaction spreading beyond test site). Other effects were reported on a separate scale from 0 (no evidence) to 7 (small petechial eruptions or scabs). |
| 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 | Participants in the Phesgo OBDS arm completed the device monitoring questionnaire the injection with the OBDS. The questionnaire assessed the following criteria: ease of device attachment, attachment during the injection, ease of device removal, and overall wearing comfort, which were each rated on a three-point scale as Good, Acceptable, or Poor. |
| Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Day 1 | Details of performance and ease of use of the on-body delivery system (OBDS) were reported by site staff, using the device monitoring questionnaire in the eCRF. This included the following: Preparation of the injection site, Preparation of the OBDS, Prefilled cartridge inspection before insertion in the OBDS, Positioning and attachment of the OBDS on the anterior thigh, Drug delivery, and OBDS administration failures. |
| Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Baseline, once between Days 20 and 35, and once between Days 56 and 63 | Echocardiography was used to assess left ventricular ejection fraction (LVEF) values. The screening LVEF assessment had to be performed within ≤28 days prior to randomization and the LVEF value must have been ≥55% to be eligible for the study. |
| 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 | — |
Countries
Australia, New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) was administered by a healthcare professional subcutaneously (SC) into the participant's anterior thigh on Day 1, using a handheld syringe with hypodermic needle. | 76 |
| Arm 2: PH FDC SC Using the OBDS A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) was administered by a healthcare professional subcutaneously (SC) into the participant's anterior thigh on Day 1, using the on-body delivery system (OBDS). | 75 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Reason Not Specified | 4 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Arm 1: PH FDC SC Using a Handheld Syringe | Arm 2: PH FDC SC Using the OBDS |
|---|---|---|---|
| Age, Continuous | 29.0 Years | 29.0 Years | 29.0 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 7 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 133 Participants | 68 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 2 Participants |
| Number of Participants by Weight Category (>75 kg vs. ≤75 kg) ≤75 kg | 41 Participants | 21 Participants | 20 Participants |
| Number of Participants by Weight Category (>75 kg vs. ≤75 kg) >75 kg | 110 Participants | 55 Participants | 55 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 15 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 17 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) White | 89 Participants | 44 Participants | 45 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 151 Participants | 76 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 74 |
| other Total, other adverse events | 70 / 72 | 69 / 74 |
| serious Total, serious adverse events | 1 / 72 | 0 / 74 |
Outcome results
Primary
Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Pertuzumab
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.
Time frame: 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
Population: Per Protocol PK Analysis Population for Pertuzumab AUC0-62 (PPAP1): includes all randomized participants who were treated and adhered to the pre-specified protocol criteria for general PK analysis and for pertuzumab AUC0-62 analysis specifically.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Pertuzumab | 1671.2 μg*day/mL | Geometric Coefficient of Variation 27.5 |
| Arm 2: PH FDC SC Using the OBDS | Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Pertuzumab | 1674.6 μg*day/mL | Geometric Coefficient of Variation 23.2 |
90% CI: [0.93, 1.08]
Primary
Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Trastuzumab
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.
Time frame: 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
Population: Per Protocol PK Analysis Population for Trastuzumab AUC0-62 (TPAP1): includes all randomized participants who were treated and adhered to the pre-specified protocol criteria for general PK analysis and for trastuzumab AUC0-62 analysis specifically.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Trastuzumab | 1341.2 μg*day/mL | Geometric Coefficient of Variation 31.4 |
| Arm 2: PH FDC SC Using the OBDS | Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Trastuzumab | 1347.1 μg*day/mL | Geometric Coefficient of Variation 23.6 |
90% CI: [0.93, 1.09]
Primary
Maximum Serum Concentration (Cmax) of Pertuzumab
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.
Time frame: 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
Population: Per Protocol PK Analysis Population for Pertuzumab Cmax (PPAP2): includes all randomized participants who were treated and adhered to the pre-specified protocol criteria for general PK analysis and for pertuzumab Cmax analysis specifically.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Maximum Serum Concentration (Cmax) of Pertuzumab | 63.4 microgram per millilitre (μg/mL) | Geometric Coefficient of Variation 32.2 |
| Arm 2: PH FDC SC Using the OBDS | Maximum Serum Concentration (Cmax) of Pertuzumab | 65.8 microgram per millilitre (μg/mL) | Geometric Coefficient of Variation 24.7 |
90% CI: [0.96, 1.12]
Primary
Maximum Serum Concentration (Cmax) of Trastuzumab
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.
Time frame: 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
Population: Per Protocol PK Analysis Population for Trastuzumab Cmax (TPAP2): includes all randomized participants who were treated and adhered to the pre-specified protocol criteria for general PK analysis and for trastuzumab Cmax analysis specifically.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Maximum Serum Concentration (Cmax) of Trastuzumab | 59.8 microgram per millilitre (μg/mL) | Geometric Coefficient of Variation 33.8 |
| Arm 2: PH FDC SC Using the OBDS | Maximum Serum Concentration (Cmax) of Trastuzumab | 62.0 microgram per millilitre (μg/mL) | Geometric Coefficient of Variation 25.2 |
90% CI: [0.95, 1.13]
Secondary
Apparent Drug Clearance (CL/F) of Pertuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Apparent Drug Clearance (CL/F) of Pertuzumab | 347 millilitres per day (mL/day) | Standard Deviation 124 |
| Arm 2: PH FDC SC Using the OBDS | Apparent Drug Clearance (CL/F) of Pertuzumab | 361 millilitres per day (mL/day) | Standard Deviation 102 |
Secondary
Apparent Drug Clearance (CL/F) of Trastuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Apparent Drug Clearance (CL/F) of Trastuzumab | 469 millilitres per day (mL/day) | Standard Deviation 172 |
| Arm 2: PH FDC SC Using the OBDS | Apparent Drug Clearance (CL/F) of Trastuzumab | 481 millilitres per day (mL/day) | Standard Deviation 122 |
Secondary
Apparent Volume of Distribution (Vd/F) of Pertuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Apparent Volume of Distribution (Vd/F) of Pertuzumab | 7670 millilitres (mL) | Standard Deviation 2030 |
| Arm 2: PH FDC SC Using the OBDS | Apparent Volume of Distribution (Vd/F) of Pertuzumab | 7730 millilitres (mL) | Standard Deviation 2250 |
Secondary
Apparent Volume of Distribution (Vd/F) of Trastuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Apparent Volume of Distribution (Vd/F) of Trastuzumab | 6320 millilitres (mL) | Standard Deviation 2890 |
| Arm 2: PH FDC SC Using the OBDS | Apparent Volume of Distribution (Vd/F) of Trastuzumab | 6030 millilitres (mL) | Standard Deviation 1980 |
Secondary
Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Pertuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Pertuzumab | 1930 μg*day/mL | Standard Deviation 593 |
| Arm 2: PH FDC SC Using the OBDS | Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Pertuzumab | 1860 μg*day/mL | Standard Deviation 454 |
Secondary
Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Trastuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Trastuzumab | 1440 μg*day/mL | Standard Deviation 453 |
| Arm 2: PH FDC SC Using the OBDS | Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Trastuzumab | 1410 μg*day/mL | Standard Deviation 331 |
Secondary
Change From Baseline Diastolic Blood Pressure Over Time
Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements.
Time frame: Baseline, Days 2, 7, 22, and 63
Population: Safety population: all participants who received the single dose of study treatment. The number analyzed represents all participants with available data at a given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL at Day 2 | -1.99 beats per minute | Standard Deviation 6.86 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL at Day 22 | 3.43 beats per minute | Standard Deviation 7.13 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Diastolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 70.50 beats per minute | Standard Deviation 7.55 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL at Day 63 | 3.96 beats per minute | Standard Deviation 7.86 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL at Day 7 | 3.04 beats per minute | Standard Deviation 6.82 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL - Minimum Value at Anytime | -4.58 beats per minute | Standard Deviation 7.16 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL - Maximum Value at Anytime | 8.13 beats per minute | Standard Deviation 7.11 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL - Minimum Value at Anytime | -4.30 beats per minute | Standard Deviation 6.13 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL - Maximum Value at Anytime | 8.65 beats per minute | Standard Deviation 7.13 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Diastolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 70.38 beats per minute | Standard Deviation 7.2 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL at Day 2 | -2.12 beats per minute | Standard Deviation 6.49 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL at Day 7 | 2.62 beats per minute | Standard Deviation 7.04 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL at Day 22 | 4.16 beats per minute | Standard Deviation 7.67 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Diastolic Blood Pressure Over Time | Change from BL at Day 63 | 3.64 beats per minute | Standard Deviation 8.36 |
Secondary
Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time
Echocardiography was used to assess left ventricular ejection fraction (LVEF) values. The screening LVEF assessment had to be performed within ≤28 days prior to randomization and the LVEF value must have been ≥55% to be eligible for the study.
Time frame: Baseline, once between Days 20 and 35, and once between Days 56 and 63
Population: Safety population: all participants who received the single dose of study treatment. The number analyzed represents all participants with available data at a given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Change from BL - Day 20 to 35 | 0.10 Percentage points of LVEF | Standard Deviation 4.88 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Change from BL - Minimum Value at Anytime | -2.09 Percentage points of LVEF | Standard Deviation 4.39 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Change from BL - Day 56 to 63 | -0.87 Percentage points of LVEF | Standard Deviation 5.04 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Change from BL - Maximum Value at Anytime | 1.32 Percentage points of LVEF | Standard Deviation 5.01 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Baseline (BL) - Value at Visit | 61.55 Percentage points of LVEF | Standard Deviation 3.56 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Change from BL - Maximum Value at Anytime | 1.23 Percentage points of LVEF | Standard Deviation 3.7 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Baseline (BL) - Value at Visit | 60.99 Percentage points of LVEF | Standard Deviation 3.82 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Change from BL - Day 20 to 35 | -0.94 Percentage points of LVEF | Standard Deviation 4.06 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Change from BL - Day 56 to 63 | -0.20 Percentage points of LVEF | Standard Deviation 4.29 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time | Change from BL - Minimum Value at Anytime | -2.36 Percentage points of LVEF | Standard Deviation 3.84 |
Secondary
Change From Baseline Pulse Rate Over Time
Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements.
Time frame: Baseline, Days 2, 7, 22, and 63
Population: Safety population: all participants who received the single dose of study treatment. The number analyzed represents all participants with available data at a given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Pulse Rate Over Time | Change from BL at Day 7 | 1.80 beats per minute | Standard Deviation 8.63 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Pulse Rate Over Time | Change from BL at Day 63 | 2.47 beats per minute | Standard Deviation 8.64 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Pulse Rate Over Time | Change from BL at Day 2 | 7.04 beats per minute | Standard Deviation 8.51 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Pulse Rate Over Time | Change from BL - Minimum Value at Anytime | -2.49 beats per minute | Standard Deviation 7.67 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Pulse Rate Over Time | Change from BL at Day 22 | 5.40 beats per minute | Standard Deviation 11.52 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Pulse Rate Over Time | Change from BL - Maximum Value at Anytime | 14.79 beats per minute | Standard Deviation 15.06 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Pulse Rate Over Time | Baseline (BL) - Value at Visit | 58.24 beats per minute | Standard Deviation 9.3 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Pulse Rate Over Time | Change from BL - Maximum Value at Anytime | 13.19 beats per minute | Standard Deviation 12.09 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Pulse Rate Over Time | Baseline (BL) - Value at Visit | 59.30 beats per minute | Standard Deviation 10.89 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Pulse Rate Over Time | Change from BL at Day 2 | 6.51 beats per minute | Standard Deviation 10.86 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Pulse Rate Over Time | Change from BL at Day 7 | 4.34 beats per minute | Standard Deviation 11.39 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Pulse Rate Over Time | Change from BL at Day 22 | 5.14 beats per minute | Standard Deviation 11.91 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Pulse Rate Over Time | Change from BL at Day 63 | 4.16 beats per minute | Standard Deviation 10.87 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Pulse Rate Over Time | Change from BL - Minimum Value at Anytime | -1.78 beats per minute | Standard Deviation 9.17 |
Secondary
Change From Baseline Respiratory Rate Over Time
Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements.
Time frame: Baseline, Days 2, 7, 22, and 63
Population: Safety population: all participants who received the single dose of study treatment. The number analyzed represents all participants with available data at a given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Respiratory Rate Over Time | Change from BL at Day 7 | 0.00 breaths per minute | Standard Deviation 2.31 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Respiratory Rate Over Time | Change from BL at Day 63 | -0.19 breaths per minute | Standard Deviation 2.3 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Respiratory Rate Over Time | Change from BL at Day 2 | -0.22 breaths per minute | Standard Deviation 2.22 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Respiratory Rate Over Time | Change from BL - Minimum Value at Anytime | -1.86 breaths per minute | Standard Deviation 1.69 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Respiratory Rate Over Time | Change from BL at Day 22 | -0.34 breaths per minute | Standard Deviation 1.68 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Respiratory Rate Over Time | Change from BL - Maximum Value at Anytime | 1.44 breaths per minute | Standard Deviation 1.96 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Respiratory Rate Over Time | Baseline (BL) - Value at Visit | 15.71 breaths per minute | Standard Deviation 1.61 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Respiratory Rate Over Time | Change from BL - Maximum Value at Anytime | 1.93 breaths per minute | Standard Deviation 2.08 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Respiratory Rate Over Time | Baseline (BL) - Value at Visit | 15.50 breaths per minute | Standard Deviation 1.49 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Respiratory Rate Over Time | Change from BL at Day 2 | -0.03 breaths per minute | Standard Deviation 2.39 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Respiratory Rate Over Time | Change from BL at Day 7 | 0.04 breaths per minute | Standard Deviation 2.1 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Respiratory Rate Over Time | Change from BL at Day 22 | 0.53 breaths per minute | Standard Deviation 2.04 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Respiratory Rate Over Time | Change from BL at Day 63 | 0.15 breaths per minute | Standard Deviation 2.61 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Respiratory Rate Over Time | Change from BL - Minimum Value at Anytime | -1.64 breaths per minute | Standard Deviation 2 |
Secondary
Change From Baseline Systolic Blood Pressure Over Time
Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements.
Time frame: Baseline, Days 2, 7, 22, and 63
Population: Safety population: all participants who received the single dose of study treatment. The number analyzed represents all participants with available data at a given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Systolic Blood Pressure Over Time | Change from BL at Day 7 | 4.55 beats per minute | Standard Deviation 7.14 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Systolic Blood Pressure Over Time | Change from BL at Day 63 | 4.70 beats per minute | Standard Deviation 9.51 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Systolic Blood Pressure Over Time | Change from BL at Day 2 | -1.44 beats per minute | Standard Deviation 7.9 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Systolic Blood Pressure Over Time | Change from BL - Minimum Value at Anytime | -4.68 beats per minute | Standard Deviation 7.97 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Systolic Blood Pressure Over Time | Change from BL at Day 22 | 3.60 beats per minute | Standard Deviation 10.76 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Systolic Blood Pressure Over Time | Change from BL - Maximum Value at Anytime | 11.17 beats per minute | Standard Deviation 9.96 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Change From Baseline Systolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 118.33 beats per minute | Standard Deviation 9.19 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Systolic Blood Pressure Over Time | Change from BL - Maximum Value at Anytime | 12.78 beats per minute | Standard Deviation 11.13 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Systolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 116.09 beats per minute | Standard Deviation 9.68 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Systolic Blood Pressure Over Time | Change from BL at Day 2 | 0.61 beats per minute | Standard Deviation 9.02 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Systolic Blood Pressure Over Time | Change from BL at Day 7 | 4.99 beats per minute | Standard Deviation 9.2 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Systolic Blood Pressure Over Time | Change from BL at Day 22 | 5.23 beats per minute | Standard Deviation 10.7 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Systolic Blood Pressure Over Time | Change from BL at Day 63 | 5.53 beats per minute | Standard Deviation 9.64 |
| Arm 2: PH FDC SC Using the OBDS | Change From Baseline Systolic Blood Pressure Over Time | Change from BL - Minimum Value at Anytime | -3.51 beats per minute | Standard Deviation 8 |
Secondary
Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device
Details of performance and ease of use of the on-body delivery system (OBDS) were reported by site staff, using the device monitoring questionnaire in the eCRF. This included the following: Preparation of the injection site, Preparation of the OBDS, Prefilled cartridge inspection before insertion in the OBDS, Positioning and attachment of the OBDS on the anterior thigh, Drug delivery, and OBDS administration failures.
Time frame: Day 1
Population: The analysis only included healthcare professionals that treated participants in Arm 2: PH FDC SC Using OBDS who received the single dose of study treatment.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Was the Injection Site Prepared as per Protocol? | Yes | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Was the Injection Site Prepared as per Protocol? | No | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Was the Injection Device Prepared as per Protocol? | Yes | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Was the Injection Device Prepared as per Protocol? | No | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Was the Body Positioning of the Device Compliant with Protocol? | Yes | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Was the Body Positioning of the Device Compliant with Protocol? | No | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Were There any Findings from the Cartridge Inspection? | Yes | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Were There any Findings from the Cartridge Inspection? | No | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Were There any Issues with the Attachment of the Device to the Body? | Yes | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Were There any Issues with the Attachment of the Device to the Body? | No | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Did you Experience any Device Failure? | Yes | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Did you Experience any Device Failure? | No | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Has Needle Been Inserted? | Yes | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Has Needle Been Inserted? | No | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Has Another Device Been Used? | Yes | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device | Has Another Device Been Used? | No | 74 Participants |
Secondary
Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire
Participants in the Phesgo OBDS arm completed the device monitoring questionnaire the injection with the OBDS. The questionnaire assessed the following criteria: ease of device attachment, attachment during the injection, ease of device removal, and overall wearing comfort, which were each rated on a three-point scale as Good, Acceptable, or Poor.
Time frame: Day 1
Population: The analysis only included participants in Arm 2: PH FDC SC Using OBDS who received the single dose of study treatment.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Ease of Device Attachment | Good | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Ease of Device Attachment | Acceptable | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Ease of Device Attachment | Poor | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Attachment of Device During Injection | Good | 73 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Attachment of Device During Injection | Acceptable | 1 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Attachment of Device During Injection | Poor | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Ease of Device Removal | Good | 67 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Ease of Device Removal | Acceptable | 6 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Ease of Device Removal | Poor | 1 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Overall Wearing Comfort | Good | 67 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Overall Wearing Comfort | Acceptable | 7 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants by Their Ratings of the Comfort of Wearing the On-Body Delivery System Device, as Reported in the Device Monitoring Questionnaire | Overall Wearing Comfort | Poor | 0 Participants |
Secondary
Number of Participants With Adverse Events Based on Laboratory Test Abnormalities
Not every laboratory abnormality qualified as an adverse event. A laboratory test result had to be reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; was clinically significant in the investigator's judgment.
Time frame: From Baseline until Day 63
Population: Safety population: all participants who received the single dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Transaminases increased | 1 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Anaemia | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Alanine aminotransferase increased | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Hepatic enzyme increased | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Neutropenia | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Hepatic enzyme increased | 1 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Transaminases increased | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Alanine aminotransferase increased | 1 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Anaemia | 1 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Adverse Events Based on Laboratory Test Abnormalities | Neutropenia | 1 Participants |
Secondary
Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator
For safety monitoring purposes, the investigator was required to review, sign, and date all electrocardiogram (ECG) reports. Any morphologic waveform changes or other ECG abnormalities were documented by the investigator. Post-baseline, if all examinations were normal, then it was categorized as 'Normal'. If any abnormality was reported, then it was categorized as 'Abnormal'. 'Clinically significant' is a subset of the abnormal category.
Time frame: At Baseline (predose) and Post-Baseline (postdose Days 2, 7, 22, and 63)
Population: Safety population: all participants who received the single dose of study treatment. The number analyzed represents all participants with available data at baseline and at least at one post-baseline timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Baseline: Abnormal ECG | 24 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Post-Baseline: Normal ECG | 42 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Baseline: Normal ECG | 48 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Baseline: Abnormal and Clinically Significant ECG | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Post-Baseline: Abnormal and Clinically Significant ECG | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Post-Baseline: Abnormal ECG | 30 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Post-Baseline: Abnormal and Clinically Significant ECG | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Baseline: Normal ECG | 42 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Baseline: Abnormal ECG | 32 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Baseline: Abnormal and Clinically Significant ECG | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Post-Baseline: Normal ECG | 35 Participants |
| Arm 2: PH FDC SC Using the OBDS | Number of Participants With Normal or Abnormal Electrocardiogram Results at Baseline and Post-Baseline Anytime, as Determined by the Investigator | Post-Baseline: Abnormal ECG | 39 Participants |
Secondary
Number of Participants With Skin Irritation and Sensitization Reactions at the Injection Site, as Reported by Investigators in the Device Monitoring Questionnaire
Skin irritation and sensitization reactions at the site of injection caused by the adhesion of the OBDS to the skin were assessed by the study staff using the device monitoring questionnaire in the eCRF. Dermal effects were reported on a scale from 0 (no evidence or irritation) to 7 (strong reaction spreading beyond test site). Other effects were reported on a separate scale from 0 (no evidence) to 7 (small petechial eruptions or scabs).
Time frame: Prior to injection and after injection on Day 1
Population: The analysis only included healthcare professionals that treated participants in Arm 2: PH FDC SC Using OBDS who received the single dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | 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, Dermal Effects: 0 - No Evidence or Irritation | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Skin Irritation and Sensitization Reactions at the Injection Site, as Reported by Investigators in the Device Monitoring Questionnaire | After Injection, Dermal Effects: 0 - No Evidence or Irritation | 62 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Skin Irritation and Sensitization Reactions at the Injection Site, as Reported by Investigators in the Device Monitoring Questionnaire | After Injection, Dermal Effects: 1 - Minimal Erythema | 12 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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, Other Effects: 0 - No Evidence or Irritation | 74 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Skin Irritation and Sensitization Reactions at the Injection Site, as Reported by Investigators in the Device Monitoring Questionnaire | After Injection, Other Effects: 0 - No Evidence or Irritation | 73 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | Number of Participants With Skin Irritation and Sensitization Reactions at the Injection Site, as Reported by Investigators in the Device Monitoring Questionnaire | After Injection, Other Effects: 1 - Slight Glazed Appearance | 1 Participants |
Secondary
Observed Serum Concentration of Pertuzumab on Day 22
Time frame: Day 22
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. Only participants who provided PK samples on Day 22 were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Observed Serum Concentration of Pertuzumab on Day 22 | 34.2 microgram per millilitre (μg/mL) | Standard Deviation 10.6 |
| Arm 2: PH FDC SC Using the OBDS | Observed Serum Concentration of Pertuzumab on Day 22 | 34.6 microgram per millilitre (μg/mL) | Standard Deviation 8.79 |
Secondary
Observed Serum Concentration of Pertuzumab on Day 63
Time frame: Day 63
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. Only participants who provided PK samples on Day 63 were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Observed Serum Concentration of Pertuzumab on Day 63 | 6.23 microgram per millilitre (μg/mL) | Standard Deviation 3.64 |
| Arm 2: PH FDC SC Using the OBDS | Observed Serum Concentration of Pertuzumab on Day 63 | 6.23 microgram per millilitre (μg/mL) | Standard Deviation 5.42 |
Secondary
Observed Serum Concentration of Trastuzumab on Day 22
Time frame: Day 22
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. Only participants who provided PK samples on Day 22 were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Observed Serum Concentration of Trastuzumab on Day 22 | 29.9 microgram per millilitre (μg/mL) | Standard Deviation 10.7 |
| Arm 2: PH FDC SC Using the OBDS | Observed Serum Concentration of Trastuzumab on Day 22 | 29.5 microgram per millilitre (μg/mL) | Standard Deviation 6.72 |
Secondary
Observed Serum Concentration of Trastuzumab on Day 63
Time frame: Day 63
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. Only participants who provided PK samples on Day 63 were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Observed Serum Concentration of Trastuzumab on Day 63 | 1.00 microgram per millilitre (μg/mL) |
| Arm 2: PH FDC SC Using the OBDS | Observed Serum Concentration of Trastuzumab on Day 63 | 1.00 microgram per millilitre (μg/mL) |
Secondary
Observed Time to Maximum Serum Concentration (Tmax) of Pertuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Observed Time to Maximum Serum Concentration (Tmax) of Pertuzumab | 4.00 Days |
| Arm 2: PH FDC SC Using the OBDS | Observed Time to Maximum Serum Concentration (Tmax) of Pertuzumab | 4.00 Days |
Secondary
Observed Time to Maximum Serum Concentration (Tmax) of Trastuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Observed Time to Maximum Serum Concentration (Tmax) of Trastuzumab | 4.01 Days |
| Arm 2: PH FDC SC Using the OBDS | Observed Time to Maximum Serum Concentration (Tmax) of Trastuzumab | 4.00 Days |
Secondary
Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale
Pain intensity scores were assessed by the participants using the Visual Analog Scale (VAS) on a line measuring between 0 mm ('no pain') and 100 mm ('unbearable pain'). The VAS was completed in both study arms to assess the level of pain experienced by the participant in relation to the injection of Phesgo. On Day 1, pain assessments were performed prior to, during, and immediately after injection of Phesgo when the needle or device was removed, and 2 hours after injection.
Time frame: Day 1: pre-dose, during drug injection, after drug injection while removing the device or syringe, and 2 hours after drug injection
Population: Safety population: all participants who received the single dose of study treatment. The number analyzed indicates all participants who responded to the questionnaire at a given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale | Prior to Injection | 0.68 score on a scale | Standard Deviation 1.45 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale | During Injection | 6.85 score on a scale | Standard Deviation 8.79 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale | Immediately Post-Injection | 8.56 score on a scale | Standard Deviation 12.62 |
| Arm 1: PH FDC SC Using a Handheld Syringe | Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale | 2 Hours After Injection | 3.11 score on a scale | Standard Deviation 5.29 |
| Arm 2: PH FDC SC Using the OBDS | Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale | 2 Hours After Injection | 1.62 score on a scale | Standard Deviation 5.97 |
| Arm 2: PH FDC SC Using the OBDS | Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale | Prior to Injection | 0.50 score on a scale | Standard Deviation 1.52 |
| Arm 2: PH FDC SC Using the OBDS | Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale | Immediately Post-Injection | 5.04 score on a scale | Standard Deviation 7.82 |
| Arm 2: PH FDC SC Using the OBDS | Pain Score at the Injection Site, Assessed by the Participant Using the 100-millimetre (mm) Visual Analog Scale | During Injection | 8.95 score on a scale | Standard Deviation 10.28 |
Secondary
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)
The adverse event (AE) severity grading scale NCI CTCAE v5.0 was used for assessing AE severity. Any AEs for which the NCI CTCAE v5.0 did not provide a grading scale, the standard four-point scale from 1 to 4 (mild, moderate, severe, life-threatening) was used. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade. AEs to monitor included administration-related reactions, hypersensitivity and anaphylaxis, diarrhoea, rash, cardiac dysfunction, neutropenia or febrile neutropenia, mucositis, and interstitial lung disease.
Time frame: From study drug dose until safety follow-up visit (up to 7 months)
Population: Safety population: all participants who received the single dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | Any Adverse Event (AE) | 70 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE with Fatal Outcome | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | Serious AE | 1 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | Related Serious AE | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | Grade 3 to 4 AE | 1 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE Leading to Drug Interruption | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | Device Related AE | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | Any AE to Monitor | 63 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Anaphylaxis and Hypersensitivity, Any Grade | 48 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Anaphylaxis and Hypersensitivity, Grade ≥3 | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Infusion/Admin. Related Reactions Within 24 hours, Any Grade | 62 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Infusion/Admin. Related Reactions Within 24 hours, Grade ≥3 | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Rash/Skin Reactions, Any Grade | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Diarrhoea, Any Grade | 17 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Diarrhoea, Grade ≥3 | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Cardiac Dysfunction, Any Grade | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Interstitial Lung Disease, Any Grade | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Neutropenia/Febrile Neutropenia, Any Grade | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Neutropenia/Febrile Neutropenia, Grade ≥3 | 0 Participants |
| Arm 1: PH FDC SC Using a Handheld Syringe | 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) | AE to Monitor: Serious Mucositis, Any Grade | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Neutropenia/Febrile Neutropenia, Any Grade | 1 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | Any Adverse Event (AE) | 71 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Infusion/Admin. Related Reactions Within 24 hours, Any Grade | 55 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE with Fatal Outcome | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Cardiac Dysfunction, Any Grade | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | Serious AE | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Infusion/Admin. Related Reactions Within 24 hours, Grade ≥3 | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | Related Serious AE | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Serious Mucositis, Any Grade | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | Grade 3 to 4 AE | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Rash/Skin Reactions, Any Grade | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE Leading to Drug Interruption | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Interstitial Lung Disease, Any Grade | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | Device Related AE | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Diarrhoea, Any Grade | 9 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | Any AE to Monitor | 59 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Neutropenia/Febrile Neutropenia, Grade ≥3 | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Anaphylaxis and Hypersensitivity, Any Grade | 36 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Diarrhoea, Grade ≥3 | 0 Participants |
| Arm 2: PH FDC SC Using the OBDS | 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) | AE to Monitor: Anaphylaxis and Hypersensitivity, Grade ≥3 | 0 Participants |
Secondary
Terminal Elimination Half-Life (t1/2) of Pertuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Terminal Elimination Half-Life (t1/2) of Pertuzumab | 15.6 Days |
| Arm 2: PH FDC SC Using the OBDS | Terminal Elimination Half-Life (t1/2) of Pertuzumab | 15.1 Days |
Secondary
Terminal Elimination Half-Life (t1/2) of Trastuzumab
Time frame: 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
Population: The Per Protocol PK Population (PAP) includes all randomized participants who were treated and adhered to the pre-specified protocol criteria. The number analyzed includes participants in the PAP with adequate concentration profiles, which allowed for individual PK parameters to be estimated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: PH FDC SC Using a Handheld Syringe | Terminal Elimination Half-Life (t1/2) of Trastuzumab | 8.93 Days |
| Arm 2: PH FDC SC Using the OBDS | Terminal Elimination Half-Life (t1/2) of Trastuzumab | 8.43 Days |