Clinical trial NCT05275010: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Male Subjects
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-03-11
Enrollment: 151
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
measure: 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
measure: 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
measure: 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
Secondary outcomes:
measure: Observed Serum Concentration of Pertuzumab on Day 22
timeFrame: Day 22
measure: Observed Serum Concentration of Trastuzumab on Day 22
timeFrame: Day 22
measure: Observed Serum Concentration of Pertuzumab on Day 63
timeFrame: Day 63
measure: Observed Serum Concentration of Trastuzumab on Day 63
timeFrame: Day 63
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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)
measure: 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
measure: Change From Baseline Pulse Rate Over Time
timeFrame: Baseline, Days 2, 7, 22, and 63
measure: Change From Baseline Respiratory Rate Over Time
timeFrame: Baseline, Days 2, 7, 22, and 63
measure: Change From Baseline Systolic Blood Pressure Over Time
timeFrame: Baseline, Days 2, 7, 22, and 63
measure: Change From Baseline Diastolic Blood Pressure Over Time
timeFrame: Baseline, Days 2, 7, 22, and 63
measure: 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)
measure: Number of Participants With Adverse Events Based on Laboratory Test Abnormalities
timeFrame: From Baseline until Day 63
measure: 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
measure: 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
measure: 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
measure: Number of Healthcare Professionals by Their Responses to the Device Monitoring Questionnaire Regarding Use of the On-Body Delivery System Device
timeFrame: Day 1
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Q-Pharm Pty Ltd; Nucleus Network Brisbane Clinic
state: Queensland
city: Adelaide
country: Australia
facility: CMAX Pty Ltd
state: South Australia
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
state: Western Australia
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research - Auckland
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research - Christchurch
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: