A PHASE 1, RANDOMIZED, DOUBLE BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY AND PHARMACOKINETICS FOLLOWING SINGLE INTRAVENOUS DOSE OF PF-06823859 IN JAPANESE HEALTHY PARTICIPANTS
Overview
- Phase
- Phase 1
- Intervention
- PF-06823859
- Conditions
- Healthy
- Sponsor
- Pfizer
- Enrollment
- 13
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
Purpose of the study is to evaluate the safety, tolerability, immunogenicity and pharmacokinetics (PK) of PF-06823859 following a single intravenous dose of PF-06823859 300 and 900 mg in Japanese healthy adult participants.
Detailed Description
Approximately 12 participants are planned to be enrolled into the study. The study consists of 2 cohorts, and approximately 5 participants will be randomized to PF-06823859 and approximately 1 participant will be randomized to placebo in each cohort.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female participants must be 20 to 55 years of age, inclusive, at the time of signing the Informed Consent Document (ICD).
- •Participants must have 4 biologically Japanese grandparents born in Japan.
- •Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and 12 lead electrocardiogram (ECG).
- •Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- •Body Mass Index (BMI) of 17.5 to 25 kg/m2; and a total body weight \>50 kg (110 lb).
- •Informed Consent:
- •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, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- •History of human immunodeficiency virus (HIV) infection, hepatitis C or syphilis; positive testing for HIV, hepatitis C antibody (HCVAb) or syphilis at screening.
- •Infection with hepatitis b virus (HBV)
- •Clinically significant abnormality, including but not limited to current, active tuberculosis (TB) or previous inactive TB, general infections, heart failure or malignancy, on chest X ray performed at screening or within 12 weeks of screening.
- •History of autoimmune disorders.
- •History of allergic or anaphylactic reaction to a therapeutic drug or any components in the study intervention.
- •Participants with clinically significant infections, based on which the investigator judges that the participant should not be enrolled in the study, within 28 days prior to the screening visit.
- •Participants with a fever, based on which the investigator judges that the participant should not be enrolled in the study, within the last 7 days prior to dosing.
- •Participants who have evidence of tuberculosis infection.
- •Participants who have been treated or are currently being treated for active or latent tuberculosis infection are to be excluded.
Arms & Interventions
PF-06823859 high
Participants will receive single intravenous infusion.
Intervention: PF-06823859
PF-06823859 low
Participants will receive single intravenous infusion.
Intervention: PF-06823859
Placebo
Participants will receive single intravenous infusion.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 up to maximum of Day 157
Adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect and suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. TEAEs were the events between first dose of study drug and up to Day 157, that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious (if occurred) and all non-serious adverse events.
Number of Participants With Infusion Related Reaction (IRR)
Time Frame: Day 1 up to maximum of Day 157
IRR included AEs potentially related to infusion related reaction and was determined by blind medical review prior to the database release.
Number of Participants With Electrocardiogram (ECG) Abnormalities of Pre-defined Criteria
Time Frame: From baseline (pre-dose measurement at Day 1) up to Day 157
Criteria for ECG abnormalities: maximum PR interval \>=300 milliseconds (msec); maximum increase in PR interval from baseline \>=25 percent (%) for baseline value of \>200 msec; maximum increase in PR interval from baseline \>=50% for baseline value of less than or equal to (\<=) 200 msec; maximum QRS interval \>=140 msec and maximum increase from baseline \>=50%; QT interval of \>=500 msec; QTcF interval (Fridericia's Correction of QTc interval) mild: \>=450 msec to \<480 msec, moderate: \>=480 msec to \<500 msec; increase from baseline \>=30 msec to \<60 msec and severe: \>=500 msec; increase from baseline \>=60 msec.
Number of Participants With Viral Infection
Time Frame: Day 1 up to maximum of Day 157
Number of Participants With Infusion Site Reaction
Time Frame: From start of study intervention infusion up to 60 minutes on Day 1
Participants were monitored from start of study intervention infusion until the end of infusion to assess the infusion sites for erythema, induration, ecchymosis, pain, and pruritus, or other observed characteristics after study intervention.
Number of Participants With Laboratory Test Abnormalities
Time Frame: Day 1 up to maximum of Day 157
Laboratory test abnormalities included hematology: basophils/leukocytes greater than (\>)1.2\* upper limit of normal (ULN), eosinophils/leukocytes \>1.2\* ULN, monocytes/leukocytes \>1.2\* ULN; clinical chemistry: bilirubin \> 1.5\* ULN, aspartate aminotransferase \>3.0\* ULN, urate \>1.2\* ULN; urinalysis: ketones greater than or equal to (\>=)1, urine hemoglobin \>=1.
Number of Participants With Vital Sign Abnormalities of Pre-defined Criteria
Time Frame: From baseline (pre-dose measurement at Day 1) up to Day 157
Vital sign abnormalities were categorized as: a) supine systolic blood pressure: minimum: less than (\<) 90 millimeter of mercury (mmHg), maximum decrease from baseline: greater than or equal to (\>=) 30 mmHg, maximum increase from baseline: \>=30 mmHg; b) supine diastolic blood pressure: minimum: \<50 mmHg, maximum decrease from baseline: \>=20 mmHg, maximum increase from baseline: \>=20 mmHg; c) supine pulse rate: minimum \<40 beats per minute (bpm), maximum \>120 bpm. Number of participants with any vital sign abnormality were reported in this outcome measure.
Secondary Outcomes
- Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Dose Normalized AUCinf (AUCinf [dn]) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Dose Normalized AUClast (AUClast [dn]) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Area Under the Curve From Time Zero to 28 Days (672 Hours) Post-Dose (AUC28day) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48, 96, 336 and 672 hours post dose on Day 1)
- Dose Normalized Cmax (Cmax [dn]) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Maximum Observed Serum Concentration (Cmax) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Mean Residence Time (MRT) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Area Under the Curve From Time Zero to 14 Days (336 Hours) Post-Dose (AUC14day) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48, 96 and 336 hours post dose on Day 1)
- Terminal Half-Life (t1/2) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Systemic Clearance (CL) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Steady-State Volume of Distribution (Vss) of PF-06823859(Pre dose on Day 1; 1, 2, 6, 12, 24, 48 and 96 hours post-dose on Day 1; Anytime during site visit at Day 15, 29, 43, 57, 71, 99, 127, 157)
- Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) for PF-06823859(Day 1 maximum up to Day 157)