Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis, inflammatory skin disease
Brief summary
This is the first time PF-07242813 will be given to humans. The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of PF-07242813 in healthy participants and in participants with moderate to severe atopic dermatitis. An additional goal is to assess the pharmacodynamics of PF-07242813 in participants with moderate to severe AD, including potential effects on clinical signs and symptoms.
Interventions
DRUGPF-07242813
PF-07242813 given intravenously or subcutaneous
DRUGPlacebo
Placebo given intravenously or subcutaneous
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1 (Healthy Volunteer Cohorts): * BMI of 17.5 to 30.5 kg/m2; and BW\>50 kg (110 lbs) * Overtly healthy as determined by medical evaluation including medical history, physical examination, vital sign assessments, temperature, 12-lead ECGs, laboratory tests * Japanese cohort: healthy adults of Japanese descent, where parents and grandparents are Japanese * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol Inclusion Criteria Part 2 (Atopic Dermatitis Cohort): * Have a clinical diagnosis of chronic atopic dermatitis (also known as atopic eczema) for approximately 1 year prior to Day 1 and have the diagnosis of AD confirmed (Hanifin and Rajka criteria of AD). * Either have had an inadequate response to treatment with topical medications (for at least 4 consecutive weeks within 1 year of the first dose of the study drug) OR Have a documented reason why topical treatments are considered medically inappropriate (eg, because of important side effects or safety risks) within the last year. * Have moderate to severe AD (defined as having an affected BSA (captured as part of EASI) ≥10%, IGA ≥3, and EASI ≥12 at both the screening and baseline visits). * Generally healthy adult, with no significant comorbidities. * Mild or moderate asthma that is well-controlled (not requiring high dose inhaled corticosteroids, systemic \[oral or parenteral\] corticosteroids, or biologic asthma treatments). * BMI of 17.5 to 40 kg/m2; and a total body weight \>50 kg (110 lbs).
Exclusion criteria
Part 1 (Healthy Volunteer Cohorts): * Evidence of active, latent, or inadequately treated infection with TB; History of HIV, hepatitis B or C infection; positive testing for HIV, HepB, HepC except HepB vaccination * Medical or psychiatric condition that may increase the risk of study participation, or inappropriate for the study in investigator's judgement * History of any lymphoproliferative disorder, evidence or history of clinically significant diseases * History of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or judged clinically significant by the investigator within 6 months * Known history of or evidence of current endocrine disease * Exposure to live or attenuated vaccines within 28 days of screening. * Have any malignancies or a history of malignancies except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ. * Allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). * Have undergone significant trauma or major surgery within 1 month of 1st dose of study drug. * Use of prescription or nonprescription drugs, dietary or herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to 1st dose of study drug. * Females taking 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. * Positive urine drug test, alcohol intake more than 14 units per week or use of tobacco/nicotine containing products more than 5 cigarettes per day. * Treatment with an investigational drug within 28 days or 5 half-lives preceding the first dose of study treatment (whichever is longer). * Abnormal BP, ECG and lab tests including AST/ALT, total bilirubin and anterior pituitary hormones, at screenings and/or baseline, based on pre-specified criteria per protocol. * Unwilling or unable to comply with the Lifestyle guidance specified in this protocol (Lifestyle Considerations section).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants With Clinically Significant Findings in ECG | From pre-dose on week 1 to week 16 | Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator. |
| Part 2: Number of Participants With TEAEs and TESAEs | From start of study treatment on Day 1 to Week 16 | An 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. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs. |
| Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | From initiation of treatment to day 71 | Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator. |
| Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | From start of study treatment on Day 1 to Day 99 | Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator. |
| Part 2: Number of Participants With Clinically Significant Findings in Vital Signs | From start of study treatment on Day 1 to Week 16 | Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator. |
| Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | Baseline (last pre-dose measurement) to Day 71 | Pre-defined criteria for laboratory parameters were hemoglobin (HGB) (\<0.8\* Lower limit normal (LLN)), Erythrocyte (Ery). Mean Corpuscular (MC) Volume (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* Upper limit normal (ULN)), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure. |
| Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities | Baseline (last pre-dose measurement) to Day 99 | Pre-defined criteria for laboratory parameters were HGB (\<0.8\* LLN), Ery MCV (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* ULN), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure. |
| Part 2: Number of Participants With Laboratory Test Abnormalities | Baseline (last pre-dose measurement) to Week 16 | Pre-defined criteria for laboratory parameters were HGB (\<0.8\* LLN), Ery MCV (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* ULN), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure. |
| Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | From pre-dose up to 6 hours post dose on Day 1 | Cardiac telemetry was collected in Part 1 SAD cohorts only. Number of participants with any cardiac telemetry abnormalities were reported in this outcome measure. |
| Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | From pre-dose on Day 1 up to Day 71 | Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, corrected QT (QTc) intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator. |
| Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG | From pre-dose on Day 1 up to Day 99 | Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator. |
| Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | From start of study treatment on Day 1 to Day 71 | An 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. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs. |
| Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | From start of study treatment on Day 1 to Day 99 | An 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. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813 | Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV | AUCinf was determined as AUClast + (Clast divided by kel), where Clast = predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel= terminal phase rate constant. |
| Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV | — |
| Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV | — |
| Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV | t1/2 was determined by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the loglinear -concentration time- curve. |
| Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose) | Area under the serum concentration time- profile over the dosing interval tau where tau=2 weeks (336 hours). |
| Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose) | — |
| Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose) | — |
| Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose) | t1/2 was determined by Loge(2) per kel, where kel was the terminal phase rate constant calculated by a linear regression of the log/linear -concentration time- curve. |
| Part 2: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6 | Baseline, Week 6 | EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD. |
| Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV | AUClast was calculated using the linear/log trapezoidal method. |
Countries
United States
Participant flow
Recruitment details
The study was conducted in 2 parts: Part 1 was conducted in healthy adult participants and Part 2 was conducted in adult participants with moderate to severe atopic dermatitis (AD).
Pre-assignment details
A total of 122 participants (57 participants in single ascending dose \[SAD\] cohorts, 40 in multiple ascending dose \[MAD\] cohorts and 25 in AD cohorts) were enrolled across 5 centers in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: 0.3 mg IV SAD Healthy participants were administered a single dose of 0.3 milligrams (mg) PF-07242813 as an intravenous (IV) infusion. | 2 |
| Part 1: 1mg IV SAD Healthy participants were administered a single dose of 1 mg PF-07242813 as an intravenous (IV) infusion. | 2 |
| Part 1: 3 mg IV SAD Healthy participants were administered a single dose of 3 mg PF-07242813 as an intravenous (IV) infusion. | 2 |
| Part 1: 10 mg IV SAD Healthy participants were administered a single dose of 10 mg PF-07242813 as an intravenous (IV) infusion. | 6 |
| Part 1: 30 mg IV SAD Healthy participants were administered a single dose of 30 mg PF-07242813 as an intravenous (IV) infusion. | 6 |
| Part 1: 100 mg IV SAD Healthy participants were administered a single dose of 100 mg PF-07242813 as an intravenous (IV) infusion. | 6 |
| Part 1: 300 mg IV SAD Healthy participants were administered a single dose of 300 mg PF-07242813 as an intravenous (IV) infusion. | 6 |
| Part 1: 1000 mg IV SAD Healthy participants were administered a single dose of 1000 mg PF-07242813 as an intravenous (IV) infusion. | 6 |
| Part 1: 1000 mg IV SAD (Japanese Cohort) Healthy Japanese participants were administered a single dose of 1000 mg PF-07242813 as an IV infusion. | 4 |
| Part 1: 15 mg SC Q2W MAD Healthy participants were administered 15 mg PF-07242813 subcutaneously every 2 weeks (Q2W) for a total of 3 doses. | 6 |
| Part 1: 50 mg SC Q2W MAD Healthy participants were administered 50 mg PF-07242813 subcutaneously every 2 weeks (Q2W) for a total of 3 doses. | 6 |
| Part 1: 150 mg SC Q2W MAD Healthy participants were administered 150 mg PF-07242813 subcutaneously every 2 weeks (Q2W) for a total of 3 doses. | 6 |
| Part 1: 300 mg SC Q2W MAD Healthy participants were administered 300 mg PF-07242813 subcutaneously every 2 weeks (Q2W) for a total of 3 doses. | 6 |
| Part 1: 500 mg IV Q2W MAD Healthy participants were administered 500 mg PF-07242813 as IV infusion every 2 weeks (Q2W) for a total of 3 doses. | 6 |
| Part 1: Placebo SAD Healthy participants were administered a single dose of placebo as an IV infusion. | 17 |
| Part 1: Placebo SC MAD Healthy participants were administered placebo every 2 weeks (Q2W) for a total of 3 doses via the SC route. | 8 |
| Part 1: Placebo IV MAD Healthy participants were administered placebo every 2 weeks (Q2W) for a total of 3 doses as an IV infusion. | 2 |
| Part 2: 1000 mg IV AD Participants with atopic dermatitis were administered a single dose of 1000 mg PF-07242813 administered as an IV Infusion. | 16 |
| Part 2: Placebo IV AD Participants with atopic dermatitis were administered a single dose of placebo as an IV infusion. | 9 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Follow-Up | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Follow-Up | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Follow-Up | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 |
| Part 1: Treatment Phase | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Treatment Phase | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Treatment Phase | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Treatment Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 |
| Part 2: Follow-Up | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 2: Treatment Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 2: Treatment Phase | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 2: Treatment Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: 0.3 mg IV SAD | Part 1: 1mg IV SAD | Part 1: 3 mg IV SAD | Part 1: 10 mg IV SAD | Part 1: 30 mg IV SAD | Part 1: 100 mg IV SAD | Part 1: 300 mg IV SAD | Part 1: 1000 mg IV SAD | Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: 15 mg SC Q2W MAD | Part 1: 50 mg SC Q2W MAD | Part 1: 150 mg SC Q2W MAD | Part 1: 300 mg SC Q2W MAD | Part 1: 500 mg IV Q2W MAD | Part 1: Placebo SAD | Part 1: Placebo SC MAD | Part 1: Placebo IV MAD | Part 2: 1000 mg IV AD | Part 2: Placebo IV AD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 44 Years | 2 Participants | 2 Participants | 2 Participants | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 6 Participants | 2 Participants | 8 Participants | 5 Participants | 1 Participants | 14 Participants | 9 Participants | 84 Participants |
| Age, Customized 45 to 64 Years | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 4 Participants | 9 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 5 Participants | 11 Participants | 7 Participants | 1 Participants | 13 Participants | 7 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 0 Participants | 1 Participants | 6 Participants | 2 Participants | 31 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 4 Participants | 3 Participants | 4 Participants | 0 Participants | 4 Participants | 6 Participants | 2 Participants | 3 Participants | 2 Participants | 10 Participants | 7 Participants | 1 Participants | 6 Participants | 4 Participants | 69 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 4 Participants | 4 Participants | 28 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 6 Participants | 5 Participants | 3 Participants | 4 Participants | 5 Participants | 2 Participants | 6 Participants | 5 Participants | 4 Participants | 6 Participants | 5 Participants | 13 Participants | 6 Participants | 2 Participants | 12 Participants | 5 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 17 | 0 / 8 | 0 / 2 | 0 / 16 | 0 / 9 |
| other Total, other adverse events | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 2 / 6 | 0 / 17 | 0 / 8 | 0 / 2 | 1 / 16 | 1 / 9 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 1 / 17 | 0 / 8 | 0 / 2 | 0 / 16 | 1 / 9 |
Outcome results
Primary
Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.
Time frame: From pre-dose on Day 1 up to Day 99
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
| Part 1: 100 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
| Part 1: 300 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
Primary
Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs
Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.
Time frame: From start of study treatment on Day 1 to Day 99
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 100 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 300 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
Primary
Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities
Pre-defined criteria for laboratory parameters were HGB (\<0.8\* LLN), Ery MCV (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* ULN), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Time frame: Baseline (last pre-dose measurement) to Day 99
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 5 Participants |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 5 Participants |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| Part 1: 100 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 6 Participants |
| Part 1: 300 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
Primary
Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs
An 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. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.
Time frame: From start of study treatment on Day 1 to Day 99
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TEAEs | 3 Participants |
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TESAEs | 0 Participants |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TEAEs | 1 Participants |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TESAEs | 0 Participants |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TEAEs | 4 Participants |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TESAEs | 0 Participants |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TEAEs | 2 Participants |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TESAEs | 1 Participants |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TEAEs | 2 Participants |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TESAEs | 0 Participants |
| Part 1: 100 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TEAEs | 5 Participants |
| Part 1: 100 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TESAEs | 0 Participants |
| Part 1: 300 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TEAEs | 1 Participants |
| Part 1: 300 mg IV SAD | Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs | TESAEs | 0 Participants |
Primary
Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG)
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, corrected QT (QTc) intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.
Time frame: From pre-dose on Day 1 up to Day 71
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
| Part 1: Placebo SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) | 0 Participants |
Primary
Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs
Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.
Time frame: From initiation of treatment to day 71
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: Placebo SAD | Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
Primary
Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities
Pre-defined criteria for laboratory parameters were hemoglobin (HGB) (\<0.8\* Lower limit normal (LLN)), Erythrocyte (Ery). Mean Corpuscular (MC) Volume (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* Upper limit normal (ULN)), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Time frame: Baseline (last pre-dose measurement) to Day 71
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| Part 1: Placebo SAD | Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities | 12 Participants |
Primary
Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An 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. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.
Time frame: From start of study treatment on Day 1 to Day 71
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 0 Participants |
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 0 Participants |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 0 Participants |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 2 Participants |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 0 Participants |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 2 Participants |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 1 Participants |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 1 Participants |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 2 Participants |
| Part 1: Placebo SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| Part 1: Placebo SAD | Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participants |
Primary
Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities
Cardiac telemetry was collected in Part 1 SAD cohorts only. Number of participants with any cardiac telemetry abnormalities were reported in this outcome measure.
Time frame: From pre-dose up to 6 hours post dose on Day 1
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention. This outcome was planned to be analyzed for SAD cohorts only as pre-specified in protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
| Part 1: Placebo SAD | Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities | 0 Participants |
Primary
Part 2: Number of Participants With Clinically Significant Findings in ECG
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.
Time frame: From pre-dose on week 1 to week 16
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 2: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
| Part 1: 1mg IV SAD | Part 2: Number of Participants With Clinically Significant Findings in ECG | 0 Participants |
Primary
Part 2: Number of Participants With Clinically Significant Findings in Vital Signs
Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.
Time frame: From start of study treatment on Day 1 to Week 16
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 2: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
| Part 1: 1mg IV SAD | Part 2: Number of Participants With Clinically Significant Findings in Vital Signs | 0 Participants |
Primary
Part 2: Number of Participants With Laboratory Test Abnormalities
Pre-defined criteria for laboratory parameters were HGB (\<0.8\* LLN), Ery MCV (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* ULN), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Time frame: Baseline (last pre-dose measurement) to Week 16
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 2: Number of Participants With Laboratory Test Abnormalities | 11 Participants |
| Part 1: 1mg IV SAD | Part 2: Number of Participants With Laboratory Test Abnormalities | 9 Participants |
Primary
Part 2: Number of Participants With TEAEs and TESAEs
An 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. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.
Time frame: From start of study treatment on Day 1 to Week 16
Population: Safety analysis set consisted of all participants randomly assigned to study intervention and who received at least one dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 2: Number of Participants With TEAEs and TESAEs | TEAEs | 4 Participants |
| Part 1: 0.3 mg IV SAD | Part 2: Number of Participants With TEAEs and TESAEs | TESAEs | 0 Participants |
| Part 1: 1mg IV SAD | Part 2: Number of Participants With TEAEs and TESAEs | TEAEs | 5 Participants |
| Part 1: 1mg IV SAD | Part 2: Number of Participants With TEAEs and TESAEs | TESAEs | 1 Participants |
Secondary
Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813
Area under the serum concentration time- profile over the dosing interval tau where tau=2 weeks (336 hours).
Time frame: Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose)
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Here, 'Number Analyzed' signifies number of participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 1 | 296000 Nanogram*hour/milliliter | Standard Deviation 47 |
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 29 | 615300 Nanogram*hour/milliliter | Standard Deviation 39 |
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 15 | 503400 Nanogram*hour/milliliter | Standard Deviation 39 |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 15 | 2294000 Nanogram*hour/milliliter | Standard Deviation 37 |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 1 | 981600 Nanogram*hour/milliliter | Standard Deviation 46 |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 29 | 3172000 Nanogram*hour/milliliter | Standard Deviation 32 |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 15 | 10160000 Nanogram*hour/milliliter | Standard Deviation 4 |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 1 | 5543000 Nanogram*hour/milliliter | Standard Deviation 23 |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 29 | 11880000 Nanogram*hour/milliliter | Standard Deviation 14 |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 1 | 12560000 Nanogram*hour/milliliter | Standard Deviation 36 |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 29 | 24500000 Nanogram*hour/milliliter | Standard Deviation 13 |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 15 | 19190000 Nanogram*hour/milliliter | Standard Deviation 20 |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 15 | 50040000 Nanogram*hour/milliliter | Standard Deviation 28 |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 1 | 27290000 Nanogram*hour/milliliter | Standard Deviation 24 |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 | Day 29 | 68840000 Nanogram*hour/milliliter | Standard Deviation 27 |
Secondary
Part 1: MAD Cohorts: Cmax for PF-07242813
Time frame: Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose)
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Here, 'Number Analyzed' signifies number of participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 1 | 1087 Nanogram per milliliter | Geometric Coefficient of Variation 43 |
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 29 | 1778 Nanogram per milliliter | Geometric Coefficient of Variation 75 |
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 15 | 1828 Nanogram per milliliter | Geometric Coefficient of Variation 33 |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 15 | 8052 Nanogram per milliliter | Geometric Coefficient of Variation 38 |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 1 | 3619 Nanogram per milliliter | Geometric Coefficient of Variation 39 |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 29 | 10470 Nanogram per milliliter | Geometric Coefficient of Variation 33 |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 15 | 39470 Nanogram per milliliter | Geometric Coefficient of Variation 19 |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 1 | 21380 Nanogram per milliliter | Geometric Coefficient of Variation 13 |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 29 | 41080 Nanogram per milliliter | Geometric Coefficient of Variation 19 |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 1 | 48550 Nanogram per milliliter | Geometric Coefficient of Variation 36 |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 29 | 83590 Nanogram per milliliter | Geometric Coefficient of Variation 16 |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 15 | 76130 Nanogram per milliliter | Geometric Coefficient of Variation 40 |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 15 | 266100 Nanogram per milliliter | Geometric Coefficient of Variation 32 |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 1 | 163800 Nanogram per milliliter | Geometric Coefficient of Variation 18 |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Cmax for PF-07242813 | Day 29 | 332900 Nanogram per milliliter | Geometric Coefficient of Variation 20 |
Secondary
Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813
t1/2 was determined by Loge(2) per kel, where kel was the terminal phase rate constant calculated by a linear regression of the log/linear -concentration time- curve.
Time frame: Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose)
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Day 29 | 111 Hours | Standard Deviation 190 |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Day 29 | 210.5 Hours | Standard Deviation 82.674 |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Day 29 | 352.8 Hours | Standard Deviation 99.704 |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Day 29 | 475.5 Hours | Standard Deviation 140.58 |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Day 29 | 474.0 Hours | Standard Deviation 98.346 |
| Unknown | Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Day 1 | — Hours | — |
| Unknown | Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | Day 15 | — Hours | — |
Secondary
Part 1: MAD Cohorts: Tmax for PF-07242813
Time frame: Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose)
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Here, 'Number Analyzed' signifies number of participants evaluable for the specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 29 | 168.50 Hours |
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 1 | 96.00 Hours |
| Part 1: 0.3 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 15 | 168.00 Hours |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 1 | 216.05 Hours |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 29 | 157.50 Hours |
| Part 1: 1mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 15 | 156.00 Hours |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 1 | 96.00 Hours |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 15 | 96.20 Hours |
| Part 1: 3 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 29 | 135.00 Hours |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 15 | 48.00 Hours |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 1 | 72.00 Hours |
| Part 1: 10 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 29 | 72.60 Hours |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 1 | 1.61 Hours |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 29 | 4.00 Hours |
| Part 1: 30 mg IV SAD | Part 1: MAD Cohorts: Tmax for PF-07242813 | Day 15 | 2.00 Hours |
Secondary
Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813
AUCinf was determined as AUClast + (Clast divided by kel), where Clast = predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel= terminal phase rate constant.
Time frame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Here, 'Overall Number of Participants Analyzed' signifies number of participants with evaluable results for this outcome measure. Data was not summarized for PK parameters if less than 3 participants had evaluable data values as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813 | 92700 Nanogram*hour/milliliter | — |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813 | 555100 Nanogram*hour/milliliter | Geometric Coefficient of Variation 28 |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813 | 1912000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 24 |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813 | 9790000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 27 |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813 | 46510000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 19 |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813 | 153700000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 21 |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813 | 173700000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 20 |
Secondary
Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813
AUClast was calculated using the linear/log trapezoidal method.
Time frame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Data was not summarized for PK parameters if less than 3 participants had evaluable data values as pre-specified in the statistical analysis plan; hence, individual values were reported for 0.3 mg IV SAD, 1 mg IV SAD and 3 mg IV SAD cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | NA Nanogram*hour/milliliter | — |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | NA Nanogram*hour/milliliter | — |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | NA Nanogram*hour/milliliter | — |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | 546200 Nanogram*hour/milliliter | Geometric Coefficient of Variation 29 |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | 1834000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 22 |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | 9349000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 23 |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | 38990000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 31 |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | 133800000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 17 |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813 | 155900000 Nanogram*hour/milliliter | Geometric Coefficient of Variation 17 |
Secondary
Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813
Time frame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Data was not summarized for PK parameters if less than 3 participants had evaluable data values as pre-specified in the statistical analysis plan; hence, individual values were reported for 0.3 mg IV SAD, 1 mg IV SAD and 3 mg IV SAD cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | NA Nanogram per milliliter | — |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | NA Nanogram per milliliter | — |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | NA Nanogram per milliliter | — |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | 3271 Nanogram per milliliter | Geometric Coefficient of Variation 23 |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | 8397 Nanogram per milliliter | Geometric Coefficient of Variation 48 |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | 33250 Nanogram per milliliter | Geometric Coefficient of Variation 34 |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | 110200 Nanogram per milliliter | Geometric Coefficient of Variation 24 |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | 362000 Nanogram per milliliter | Geometric Coefficient of Variation 11 |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813 | 445900 Nanogram per milliliter | Geometric Coefficient of Variation 10 |
Secondary
Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813
t1/2 was determined by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the loglinear -concentration time- curve.
Time frame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Here, 'Overall Number of Participants Analyzed' signifies number of participants with evaluable results for this outcome measure. Data was not summarized for PK parameters if less than 3 participants had evaluable data values as pre-specified in the statistical analysis plan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | NA Hours | — |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | 138.0 Hours | Geometric Coefficient of Variation 38.152 |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | 170.8 Hours | Geometric Coefficient of Variation 46.3 |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | 256.0 Hours | Geometric Coefficient of Variation 65.396 |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | 434.6 Hours | Geometric Coefficient of Variation 50.708 |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | 557.8 Hours | Geometric Coefficient of Variation 118.48 |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 | 545.5 Hours | Geometric Coefficient of Variation 80.707 |
Secondary
Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813
Time frame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
Population: The PK parameter set consisted of all randomized participants who received at least 1 dose of study intervention and who have at least 1 of the PK parameters of interest calculated. Data was not summarized for PK parameters if less than 3 participants had evaluable data values as pre-specified in the statistical analysis plan; hence, individual values were reported for 0.3 mg IV SAD, 1 mg IV SAD and 3 mg IV SAD cohorts.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | NA Hours |
| Part 1: 1mg IV SAD | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | NA Hours |
| Part 1: 3 mg IV SAD | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | NA Hours |
| Part 1: 10 mg IV SAD | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | 2.00 Hours |
| Part 1: 30 mg IV SAD | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | 2.00 Hours |
| Part 1: 100 mg IV SAD | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | 1.61 Hours |
| Part 1: 300 mg IV SAD | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | 2.00 Hours |
| Part 1: 1000 mg IV SAD | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | 2.00 Hours |
| Part 1: 1000 mg IV SAD (Japanese Cohort) | Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813 | 1.22 Hours |
Secondary
Part 2: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6
EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.
Time frame: Baseline, Week 6
Population: Modified Intention to Treat (mITT) population consisted of all randomized participants assigned to study intervention and who applied at least 1 dose of study intervention. One participant was randomized twice under different participant ID (PID) at two different sites. The participant was included in the efficacy analyses under the first PID. The participant enrolled under the second PID was included in mITT per mITT definition, but was excluded from efficacy analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: 0.3 mg IV SAD | Part 2: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6 | -38.2 Percent change |
| Part 1: 1mg IV SAD | Part 2: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6 | -43.8 Percent change |
p-value: 0.634390% CI: [-21.4, 32.6]ANCOVA