Clinical trial NCT05194579: Pharmacokinetic Comparability Study in Healthy Participants - PF-06881894 On-Body Injector Relative to Prefilled Syringe
Official title: A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE DOSE, 2-WAY CROSSOVER STUDY ASSESSING PHARMACOKINETIC COMPARABILITY OF TWO PF-06881894 PRESENTATIONS, ON-BODY INJECTOR AND PREFILLED SYRINGE, IN HEALTHY PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: on-body injector
OBI
febrile neutropenia
pegfilgrastim
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-01-18
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This will be an open-label, randomized, 2-treatment, 2-period, crossover single-dose study in approximately 134 healthy adult participants. Participants will be randomized into 2 sequences of treatment as described in the following table of Intervention Groups and Duration.


Eligibility criteria: Inclusion Criteria:

* Healthy male and/or female participants who, at the time of screening, are between the ages of 18 and 65 years, inclusive.
* Participants will include healthy individuals, with healthy being defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including BP and PR measurement, 12-lead ECG, chest X-ray, or clinical laboratory tests.
* Participants agree to abstain from the use of tobacco- or nicotine-containing products for at least 90 days prior to dosing and have a negative urine screen for cotinine at Screening.
* Participants agree to abstain from alcohol consumption for at least 48 hours prior to Day 1 of dosing in each study period and have a negative screen for alcohol.
* Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
* BMI between 19 and 30 kg/m2, inclusive, and body weight of not\<50 kg or \>100 kg.
* Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
* Any condition possibly affecting drug absorption (eg, injuries to subcutaneous tissue at the injection site).
* Any clinically significant, as determined by the investigator, abnormal laboratory evaluations, including HIVAb, HBVsAg, HBVcAb, HCVAb and liver function taken at Screening. The negative HIVAb status will be confirmed at Screening, and all HIV results will be maintained confidentially by the study site.
* History of malignancy, including current malignancy, with the exception of adequately treated squamous or basal cell carcinoma of the skin or cervical carcinoma in situ within 5 years.
* Surgery within the 4 months prior to Screening.
* History of splenic rupture (or participant who is asplenic), pulmonary infiltrate or pneumonia, sickle cell disease, chronic neutropenia, thrombocytopenia, or vasculitis.
* Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
* History of biological growth factor exposure, including but not limited to pegfilgrastim, filgrastim and other G-CSFs in the context of treatment, prophylaxis, peripheral blood stem cell mobilization, or previous investigational study setting. This also includes exclusion for history of interferon, epoetin, and IVIG exposure.
* Receipt of live vaccination, or exposure to communicable viral diseases such as chicken pox, varicella, mumps, measles, or COVID-19 within the 4 weeks prior to Screening.
* Use of any prescription medicine (with the exception of contraceptives) within 7 days or at least 5 half-lives, whichever was longer. Use of oral or parenteral anticoagulant or antiplatelet agents and corticosteroids should be specifically queried.
* Administration of a drug by depot injection (with the exception of depot contraception) within 30 days prior to the initial study drug administration or 5 half-lives of that drug, whichever is longer.
* Use of over the counter medications, including aspirin and non-steroidal anti-inflammatory drugs, or natural preparations (dietary supplement or herbal product) within 7 days of the first dose of PF-06881894 or at least 5 half-lives, whichever is longer. Vitamins and calcium supplements are allowed (not to exceed 100% Daily Value). As an exception, acetaminophen/paracetamol may be used at doses of ≤1 g/day. Limited use of non-prescription medications that are not believed to affect participant safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.
* Females using post-menopausal hormone replacement therapy may be eligible to participate in this study if they are willing to discontinue therapy at least 28 days prior to the first dose of study treatment and remain off hormonal therapy for the duration of the study. Hormonal contraceptives that meet the requirements of this study are allowed to be used in participants who are women of childbearing potential.
* Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention (whichever is longer) prior to study entry and/or during study participation. If a participant receives a vaccine or other medical product for the prevention or treatment of COVID-19 authorized under an Emergency Use Authorization, this would not be considered an investigational medical product.
* Hematologic laboratory abnormalities at screening or the Day -5 to Day -4 visit including leukocytosis (defined as total leukocytes \>11,000/μL), leukopenia (defined as total leukocytes \<4000/μL), neutropenia (defined as ANC \<1500/μL) or thrombocytopenia (defined as platelet count of \<150,000/μL).
* A positive urine drug test.
* A positive SARS-CoV-2 infection determined by PCR at screening or Day -5 to Day -4, or determined by a positive COVID-19 antigen test (if performed as part of an investigator site policy).
* Screening supine BP \>= 140 mm Hg (systolic) or \>= 90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is \>= 140 mm Hg (systolic) or \>= 90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
* Screening supine 12-lead ECG demonstrating QTc \>450 msec or a QRS interval \>120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the participant's eligibility.
* Participants with the following abnormalities in clinical laboratory tests at screening or the Day -5 to Day -4 visit, as assessed by the study specific laboratory will be confirmed by a single repeat test, if deemed necessary. Then the investigator (in consultation with the medical monitor) will determine if the laboratory abnormality is clinically significant and sufficient to exclude the participant from the study.

Lack of adequate hepatic reserve, defined by AST/SGOT or ALT/SGPT \>= 1.5 × ULN of the reference laboratory; TBili \>= 1.5 × ULN; participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is \<= ULN.

Lack of renal reserve, defined by serum creatinine of \>= 1.2 × ULN for reference laboratory or eGFR of \<= 80 mL/minute; or known history of glomerulonephritis.

* Drug sensitivity, allergic reaction to, or known hypersensitivity/idiosyncratic reaction to E coli -derived proteins, pegfilgrastim, filgrastim, other G-CSFs or any component of the product or known hypersensitivity to pegylated products or acrylic adhesives. Participants with the rare heredity problem of fructose intolerance are excluded due to the excipient sorbitol.
* History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) within 6 months of Screening.
* History of sensitivity to heparin or heparin-induced thrombocytopenia.
* Pregnant female participants, breastfeeding female participants, and male participants able to father children and female participants of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of study intervention.
* Blood donation (including plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing OR had a transfusion of any blood product within 90 days prior to Screening.
* Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol. Male participants with pregnant partners are not to be enrolled in the study, even if the participant is willing to comply with the contraception lifestyle requirements and use a highly effective method of contraception consistently and correctly for the duration of the study and for at least 28 days after the last dose of study intervention.
* Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Primary outcomes:
measure: Maximum Serum Concentration (Cmax) of PF-06881894
timeFrame: Within 1 hour prior to dose (Hour 0) and at 0.167 (10 min), 0.5, 1, 3, 6, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose
measure: Area Under the Serum Drug Concentration-time Profile From Time 0 to the Last Quantifiable Concentration (AUClast) of PF-06881894
timeFrame: Within 1 hour prior to dose (Hour 0) and at 0.167 (10 min), 0.5, 1, 3, 6, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose
measure: Area Under the Serum Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06881894
timeFrame: Within 1 hour prior to dose (Hour 0) and at 0.167 (10 min), 0.5, 1, 3, 6, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose
Secondary outcomes:
measure: Time for Cmax (Tmax) of PF-06881894
timeFrame: Within 1 hour prior to dose (Hour 0) and at 0.167 (10 min), 0.5, 1, 3, 6, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose
measure: Terminal Serum Elimination Half-life (t½) of PF-06881894
timeFrame: Within 1 hour prior to dose (Hour 0) and at 0.167 (10 min), 0.5, 1, 3, 6, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From the first dose on Day 1 of Period 1 to the Period 2 Day 28 Visit (up to 5 months).
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood )
state: Florida
city: Saint Paul
country: United States
facility: Prism Research LLC dba Nucleus Network
state: Minnesota
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: