A 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
- 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.
- Short title
- A 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
- Official title
- 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
- Control arm
- Active comparator
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Completed
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2023-10-03
- First posted
- 2022-03-11
- Registry last updated
- 2024-09-23
- Primary completion date
- 2023-05-14
- Start date
- 2022-05-30
- Actual participants
- Participants
- Participant count basis
- Actual
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Hoffmann-La Roche
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05275010
- ClinicalTrials.gov ID
- NCT05275010
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Parallel groups
- Purpose
- Basic science
- Masking
- No masking
Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Pertuzumab
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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.
Observed Serum Concentration of Pertuzumab on Day 22
Timeframe: Day 22
Observed Serum Concentration of Trastuzumab on Day 22
Timeframe: Day 22
Observed Serum Concentration of Pertuzumab on Day 63
Timeframe: Day 63
Observed Serum Concentration of Trastuzumab on Day 63
Timeframe: Day 63
Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Pertuzumab
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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)
Timeframe: 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.
Change From Baseline Left Ventricular Ejection Fraction (LVEF) Over Time
Timeframe: 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.
Change From Baseline Pulse Rate Over Time
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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".
And 1 more, listed on the interactive page.
- Sex
- Male
- Age groups
- Adults
- Minimum age
- 18 Years
- Maximum age
- 45 Years
- Healthy volunteers
- Yes
- 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
- 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
- Q-Pharm Pty Ltd; Nucleus Network Brisbane ClinicHerston, Australia
- CMAX Pty LtdAdelaide, Australia
- Linear Clinical Research LtdNedlands, Australia
- New Zealand Clinical Research - AucklandAuckland, New Zealand
- New Zealand Clinical Research - ChristchurchChristchurch, New Zealand
- PubMed 40514611Related publication