Healthy
Conditions
Keywords
Healthy volunteer, Healthy, IBD, Inflammatory bowel disease
Brief summary
The purpose of this clinical trial is to learn about the safety and effects of the study medicine PF-07261271 for the potential treatment of Inflammatory Bowel Disease.
Interventions
DRUGPF-07261271
IV or SC
DRUGPlacebo
IV or SC
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy individuals as determined by medical evaluation * Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
Exclusion criteria
* Clinically significant medical conditions * History of HIV infection, hepatitis B, or hepatitis C * BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) * Clinically relevant ECG abnormalities * Previous study drug administration within 30 days or 5 half-lives of first planned dose * History of drug/alcohol abuse or \>20 cigarettes/day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort | From start of study intervention (Day 1) up to end of study, approximately up to 15 months | An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the last follow-up date, were considered as TEAEs. AEs included all SAEs and Non-SAEs. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs): MD Cohort | From start of study intervention (Day 1) up to end of study, approximately of 15.5 months | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the last follow-up date, were considered as TEAEs. AEs included all SAEs and Non-SAEs. |
| Number of Participants With Serious Adverse Events (SAEs): SAD Cohort | From start of study intervention (Day 1) up to end of study, approximately up to 15 months | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAEs were defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic or other medically significant event. |
| Number of Participants With Serious Adverse Events (SAEs): MD Cohort | From start of study intervention (Day 1) up to end of study, approximately of 15.5 months | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAEs were defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic or other medically significant event. |
| Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort | From start of study intervention (Day 1) up to end of study, approximately up to 15 months | Criteria for abnormal values of vital signs: systolic blood pressure (millimeters of mercury \[mmHg\]) value less than (\<) 90 mmHg, change greater than or equal to (\>=) 30 mmHg increase, change \>= 30 mmHg decrease; diastolic blood pressure (mmHg), value \<50 mmHg, change \>=20 mmHg increase, change \>=20 mmHg decrease; pulse rate (beats per minute \[bpm\]) value \<40bpm, value greater than (\>) 120bpm. Clinical significance was determined based on investigator's discretion. |
| Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: MD Cohort | From start of study intervention (Day 1) up to end of study, approximately of 15.5 months | Criteria for abnormal values of vital signs: systolic blood pressure (mmHg) value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; diastolic blood pressure (mmHg), value \<50 mmHg, change \>=20 mmHg increase, change \>=20 mmHg decrease; pulse rate (bpm) value \< 40bpm, value \> 120bpm. Clinical significance was determined based on investigator's discretion. |
| Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort | From start of study intervention (Day 1) up to end of study, approximately up to 15 months | Criteria:Hematology(Activated partial thromboplastin time\>1.1\*upper limit of normal(ULN); Basophils &eosinophils\>1.2\*ULN; erythrocytes,hematocrit,hemoglobin,lymphocytes,neutrophils \<0.8\*lower limit of normal(LLN); leukocytes \<0.6\*LLN, \>1.5\*ULN; monocytes \>1.2\*ULN; platelets \<0.5\*LLN; prothrombin international randomized ratio &prothrombin Time \>1.1\*ULN), clinical chemistry (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase \>3.0\*ULN; albumin, protein \<0.8\*LLN, \>1.2\*ULN; bicarbonate, calcium, chloride, potassium \<0.9\*LLN,\>1.1\*ULN; bilirubin \>1.5\*ULN; creatinine \>1.3\*ULN; glucose, Glucose-FASTING \<0.6\*LLN,\>1.5\*ULN; Sodium \<0.95\*LLN,\>1.05\*ULN; Urate: \>1.2\*ULN;Urea Nitrogen: \>1.3\*ULN),urinalysis(Bacteria \> 20;epithelial cells \>=6;granular, hyaline, RBC&WBC casts \>1;ketones,leukocyte esterase, nitrite, urine glucose, urine hemoglobin, urine protein\>=1,urine erythrocytes,leukocytes \>=20;pH(scalar)\<4.5,\>8.Clinical significance determined on investigator's discretion. |
| Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: MD Cohort | From start of study intervention (Day 1) up to end of study, approximately of 15.5 months | Criteria:Hematology(Activated partial thromboplastin time\>1.1\*upper limit of normal(ULN); Basophils &eosinophils\>1.2\*ULN; erythrocytes,hematocrit,hemoglobin,lymphocytes,neutrophils \<0.8\*lower limit of normal(LLN); leukocytes \<0.6\*LLN, \>1.5\*ULN; monocytes \>1.2\*ULN; platelets \<0.5\*LLN; prothrombin international randomized ratio &prothrombin Time \>1.1\*ULN), clinical chemistry (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase \>3.0\*ULN; albumin, protein \<0.8\*LLN, \>1.2\*ULN; bicarbonate, calcium, chloride, potassium \<0.9\*LLN,\>1.1\*ULN; bilirubin \>1.5\*ULN; creatinine \>1.3\*ULN; glucose, Glucose-FASTING \<0.6\*LLN,\>1.5\*ULN; Sodium \<0.95\*LLN,\>1.05\*ULN; Urate: \>1.2\*ULN;Urea Nitrogen: \>1.3\*ULN),urinalysis(Bacteria \> 20;epithelial cells \>=6;granular, hyaline, RBC&WBC casts \>1;ketones,leukocyte esterase, nitrite, urine glucose, urine hemoglobin, urine protein\>=1,urine erythrocytes,leukocytes \>=20;pH(scalar)\<4.5,\>8.Clinical significance determined on investigator's discretion. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort | From start of study intervention (Day 1) up to end of study, approximately up to 15 months | Criteria for abnormal values of ECG parameters: pulse rate (PR) interval greater than or equal to (\>=)300 milliseconds (msec); PR interval change \>=25 percent (%) or \>=50 %, QRS interval \>=140 msec and QRS interval change: \>=50%. QT interval using Fridericia's correction (QTcF) range from 450 msec to less than (\<)480 msec, less than (\<) 480 msec to maximum less than or equal to (\<=)500 msec, \>500 msec, \<=30 to \<60 msec and \>=60 msec. Only rows which included at least 1 participant with abnormality are reported in this outcome measure. Clinical significance was determined based on investigator's discretion. |
| Number of Participants With Clinically Significant Changes in ECG Abnormalities: MD Cohort | From start of study intervention (Day 1) up to end of study, approximately of 15.5 months | Criteria for abnormal values of ECG parameters: pulse rate (PR) interval greater than or equal to (\>=)300 milliseconds (msec); PR interval change \>=25 percent (%) or \>=50 %, QRS interval \>=140 msec and QRS interval change: \>=50%. QT interval using Fridericia's correction (QTcF) range from 450 msec to less than (\<)480 msec, less than (\<) 480 msec to maximum less than or equal to (\<=)500 msec, \>500 msec, \<=30 to \<60 msec and \>=60 msec. Only rows which included at least 1 participant with abnormality are reported in this outcome measure. Clinical significance was determined based on investigator's discretion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-drug Antibodies (ADA) Against PF-07261271: SAD Cohort | Baseline up to 15 months | ADA positive was defined as ADA titer \>= 100; ADA negative defined as ADA titer \< 100. Baseline was defined as the last pre-dose measurement |
| Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Time Point (AUClast) of PF-07261271: SAD Cohort | Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose | AUClast was determined using Linear Log trapezoidal method. |
| Number of Participants With NAb Against PF-07261271: MD Cohort | Baseline up to 15.5 months | NAb was determined by electrochemiluminescent (ECL) competitive ligand binding assay using the Meso Scale Discovery (MSD) platform. |
| Number of Participants With ADA Against PF-07261271: MD Cohort | Baseline up to 15.5 months | ADA positive defined as ADA titer \>= 100; ADA negative defined as ADA titer \< 100. Baseline was defined as the last pre-dose measurement. |
| Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07261271: SAD Cohort | Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose | AUCinf was determined as AUClast + (Clast\*/kel), where Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis. |
| Maximum Plasma Concentration (Cmax) of PF-07261271: SAD Cohort | Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose | Cmax was defined as maximum serum concentration. |
| Time to Maximum Plasma Concentration (Tmax) of PF-07261271: SAD Cohort | Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose | Tmax was defined as time for Cmax. |
| Terminal Elimination Half-life (t1/2) of PF-07261271: SAD Cohort | Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose | t1/2 was determined using Loge (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear -concentration time- curve. |
| Area Under the Concentration Time Profile From Time Zero to Time Tau (τ), the Dosing Interval (AUCtau) of PF-07261271: MD Cohort | Predose and 0, 2, 4, 8, 12, 48, 96, 192, 360, 720, 744, 1224, 1584, 1944, 2664, 4104, 4824, 5544, 6264, 6984, 7704, 8424, 9144 and 11304 hours post-dose on Day 1 and 29 | AUCtau was defined as area under the concentration time profile from time zero to time tau (τ), the dosing interval, where tau=672 hours for every 4-week dosing. AUCtau was determined by Linear Log trapezoidal method. |
| Cmax of PF-07261271: MD Cohort | Predose and 0, 2, 4, 8, 12, 48, 96, 192, 360, 720, 744, 1224, 1584, 1944, 2664, 4104, 4824, 5544, 6264, 6984, 7704, 8424, 9144 and 11304 hours post-dose on Day 1 and 29 | Cmax was defined as maximum serum concentration. |
| Tmax of PF-07261271: MD Cohort | Predose and 0, 2, 4, 8, 12, 48, 96, 192, 360, 720, 744, 1224, 1584, 1944, 2664, 4104, 4824, 5544, 6264, 6984, 7704, 8424, 9144 and 11304 hours post-dose on Day 1 and 29 | Tmax was defined as time for Cmax. |
| Number of Participants With Neutralizing Antibodies (NAb) Against PF-07261271: SAD Cohort | Baseline up to 15 months | NAb was determined by electrochemiluminescent (ECL) competitive ligand binding assay using the Meso Scale Discovery (MSD) platform. |
| Terminal Elimination Half-life (t1/2) of PF-07261271: MD Cohort | Predose and 0, 2, 4, 8, 12, 48, 96, 192, 360, 720, 744, 1224, 1584, 1944, 2664, 4104, 4824, 5544, 6264, 6984, 7704, 8424, 9144 and 11304 hours post-dose on Day 1 and 29 | t1/2 was determined using Loge (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear -concentration time- curve. |
Countries
United States
Participant flow
Recruitment details
A total of 35 participants (27 participants assigned to single ascending dose \[SAD\] cohorts and 8 participants assigned in the multiple doses \[MD\] cohorts) were enrolled in the study.
Pre-assignment details
In this study, dose have been reported from dose levels 1 to 4, wherein dose level 1 is the lowest dose and dose level 4 is the highest dose received by the study participants.
Participants by arm
| Arm | Count |
|---|---|
| SAD: Placebo Healthy participants who were randomized to receive placebo matched to PF-07261271 as single IV dose on Day 1. | 8 |
| SAD: PF-07261271 Dose Level 1 Healthy participants who were randomized to receive PF-07261271 Dose Level 1 as single IV dose on Day 1. | 2 |
| SAD: PF-07261271 Dose Level 2 Healthy participants who were randomized to receive PF-07261271 Dose level 2 as single IV dose on Day 1. | 2 |
| SAD: PF-07261271 Dose Level 3 Healthy participants who were randomized to receive PF-07261271 Dose level 3 as single IV dose on Day 1. | 4 |
| SAD: PF-07261271 Dose Level 4 Healthy participants who were randomized to receive PF-07261271 Dose level 4 as single IV dose on Day 1. | 6 |
| SAD: Placebo (Japanese Participants) Healthy Japanese participants who were randomized to receive placebo matched to PF-07261271 as single dose on Day 1. | 1 |
| SAD: PF-07261271 Dose Level 4 (Japanese Participants) Healthy Japanese participants who were randomized to receive PF-07261271 Dose level 4 as single IV dose on Day 1. | 4 |
| MD: Placebo Healthy participants who were randomized to receive placebo matched to PF-07261271 as repeated subcutaneous (SC) doses on Day 1 and Day 29. | 2 |
| MD: PF-07261271 Dose Level 3 Healthy participants who were randomized to receive PF-07261271 Dose level 3 repeated escalating SC doses on Day 1 and Day 29. | 6 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | SAD: Placebo | Total | MD: PF-07261271 Dose Level 3 | MD: Placebo | SAD: PF-07261271 Dose Level 4 (Japanese Participants) | SAD: Placebo (Japanese Participants) | SAD: PF-07261271 Dose Level 4 | SAD: PF-07261271 Dose Level 3 | SAD: PF-07261271 Dose Level 2 | SAD: PF-07261271 Dose Level 1 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-25 Years | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Customized 26-35 Years | 2 Participants | 12 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants |
| Age, Customized 36-45 Years | 2 Participants | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Greater than (>) 45 Years | 2 Participants | 14 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Age, Customized Less than (<) 18 Years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 29 Participants | 5 Participants | 2 Participants | 4 Participants | 1 Participants | 4 Participants | 4 Participants | 1 Participants | 2 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 |
| 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 |
| Race (NIH/OMB) Asian | 0 Participants | 6 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 |
| 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 |
| Race (NIH/OMB) White | 6 Participants | 23 Participants | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 3 Participants | 10 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 25 Participants | 4 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 3 Participants | 2 Participants | 1 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 2 | 0 / 2 | 0 / 4 | 0 / 6 | 0 / 1 | 0 / 4 | 0 / 2 | 0 / 6 |
| other Total, other adverse events | 4 / 8 | 1 / 2 | 1 / 2 | 3 / 4 | 2 / 6 | 0 / 1 | 1 / 4 | 2 / 2 | 5 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 2 | 0 / 2 | 0 / 4 | 0 / 6 | 0 / 1 | 0 / 4 | 0 / 2 | 0 / 6 |
Outcome results
Primary
Number of Participants With Clinically Significant Changes in ECG Abnormalities: MD Cohort
Criteria for abnormal values of ECG parameters: pulse rate (PR) interval greater than or equal to (\>=)300 milliseconds (msec); PR interval change \>=25 percent (%) or \>=50 %, QRS interval \>=140 msec and QRS interval change: \>=50%. QT interval using Fridericia's correction (QTcF) range from 450 msec to less than (\<)480 msec, less than (\<) 480 msec to maximum less than or equal to (\<=)500 msec, \>500 msec, \<=30 to \<60 msec and \>=60 msec. Only rows which included at least 1 participant with abnormality are reported in this outcome measure. Clinical significance was determined based on investigator's discretion.
Time frame: From start of study intervention (Day 1) up to end of study, approximately of 15.5 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Clinically Significant Changes in ECG Abnormalities: MD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Clinically Significant Changes in ECG Abnormalities: MD Cohort | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort
Criteria for abnormal values of ECG parameters: pulse rate (PR) interval greater than or equal to (\>=)300 milliseconds (msec); PR interval change \>=25 percent (%) or \>=50 %, QRS interval \>=140 msec and QRS interval change: \>=50%. QT interval using Fridericia's correction (QTcF) range from 450 msec to less than (\<)480 msec, less than (\<) 480 msec to maximum less than or equal to (\<=)500 msec, \>500 msec, \<=30 to \<60 msec and \>=60 msec. Only rows which included at least 1 participant with abnormality are reported in this outcome measure. Clinical significance was determined based on investigator's discretion.
Time frame: From start of study intervention (Day 1) up to end of study, approximately up to 15 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 2 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 3 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort | 0 Participants |
| SAD: Placebo (Japanese Participants) | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 (Japanese Participants) | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Abnormalities: SAD Cohort | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: MD Cohort
Criteria:Hematology(Activated partial thromboplastin time\>1.1\*upper limit of normal(ULN); Basophils &eosinophils\>1.2\*ULN; erythrocytes,hematocrit,hemoglobin,lymphocytes,neutrophils \<0.8\*lower limit of normal(LLN); leukocytes \<0.6\*LLN, \>1.5\*ULN; monocytes \>1.2\*ULN; platelets \<0.5\*LLN; prothrombin international randomized ratio &prothrombin Time \>1.1\*ULN), clinical chemistry (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase \>3.0\*ULN; albumin, protein \<0.8\*LLN, \>1.2\*ULN; bicarbonate, calcium, chloride, potassium \<0.9\*LLN,\>1.1\*ULN; bilirubin \>1.5\*ULN; creatinine \>1.3\*ULN; glucose, Glucose-FASTING \<0.6\*LLN,\>1.5\*ULN; Sodium \<0.95\*LLN,\>1.05\*ULN; Urate: \>1.2\*ULN;Urea Nitrogen: \>1.3\*ULN),urinalysis(Bacteria \> 20;epithelial cells \>=6;granular, hyaline, RBC&WBC casts \>1;ketones,leukocyte esterase, nitrite, urine glucose, urine hemoglobin, urine protein\>=1,urine erythrocytes,leukocytes \>=20;pH(scalar)\<4.5,\>8.Clinical significance determined on investigator's discretion.
Time frame: From start of study intervention (Day 1) up to end of study, approximately of 15.5 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: MD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: MD Cohort | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort
Criteria:Hematology(Activated partial thromboplastin time\>1.1\*upper limit of normal(ULN); Basophils &eosinophils\>1.2\*ULN; erythrocytes,hematocrit,hemoglobin,lymphocytes,neutrophils \<0.8\*lower limit of normal(LLN); leukocytes \<0.6\*LLN, \>1.5\*ULN; monocytes \>1.2\*ULN; platelets \<0.5\*LLN; prothrombin international randomized ratio &prothrombin Time \>1.1\*ULN), clinical chemistry (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase \>3.0\*ULN; albumin, protein \<0.8\*LLN, \>1.2\*ULN; bicarbonate, calcium, chloride, potassium \<0.9\*LLN,\>1.1\*ULN; bilirubin \>1.5\*ULN; creatinine \>1.3\*ULN; glucose, Glucose-FASTING \<0.6\*LLN,\>1.5\*ULN; Sodium \<0.95\*LLN,\>1.05\*ULN; Urate: \>1.2\*ULN;Urea Nitrogen: \>1.3\*ULN),urinalysis(Bacteria \> 20;epithelial cells \>=6;granular, hyaline, RBC&WBC casts \>1;ketones,leukocyte esterase, nitrite, urine glucose, urine hemoglobin, urine protein\>=1,urine erythrocytes,leukocytes \>=20;pH(scalar)\<4.5,\>8.Clinical significance determined on investigator's discretion.
Time frame: From start of study intervention (Day 1) up to end of study, approximately up to 15 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 2 | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 3 | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort | 0 Participants |
| SAD: Placebo (Japanese Participants) | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 (Japanese Participants) | Number of Participants With Clinically Significant Changes in Laboratory Abnormalities: SAD Cohort | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: MD Cohort
Criteria for abnormal values of vital signs: systolic blood pressure (mmHg) value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; diastolic blood pressure (mmHg), value \<50 mmHg, change \>=20 mmHg increase, change \>=20 mmHg decrease; pulse rate (bpm) value \< 40bpm, value \> 120bpm. Clinical significance was determined based on investigator's discretion.
Time frame: From start of study intervention (Day 1) up to end of study, approximately of 15.5 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: MD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: MD Cohort | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort
Criteria for abnormal values of vital signs: systolic blood pressure (millimeters of mercury \[mmHg\]) value less than (\<) 90 mmHg, change greater than or equal to (\>=) 30 mmHg increase, change \>= 30 mmHg decrease; diastolic blood pressure (mmHg), value \<50 mmHg, change \>=20 mmHg increase, change \>=20 mmHg decrease; pulse rate (beats per minute \[bpm\]) value \<40bpm, value greater than (\>) 120bpm. Clinical significance was determined based on investigator's discretion.
Time frame: From start of study intervention (Day 1) up to end of study, approximately up to 15 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 2 | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 3 | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort | 0 Participants |
| SAD: Placebo (Japanese Participants) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 (Japanese Participants) | Number of Participants With Clinically Significant Changes in Vital Signs Abnormalities: SAD Cohort | 0 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs): MD Cohort
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAEs were defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic or other medically significant event.
Time frame: From start of study intervention (Day 1) up to end of study, approximately of 15.5 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Serious Adverse Events (SAEs): MD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Serious Adverse Events (SAEs): MD Cohort | 0 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs): SAD Cohort
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAEs were defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic or other medically significant event.
Time frame: From start of study intervention (Day 1) up to end of study, approximately up to 15 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Serious Adverse Events (SAEs): SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Serious Adverse Events (SAEs): SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 2 | Number of Participants With Serious Adverse Events (SAEs): SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 3 | Number of Participants With Serious Adverse Events (SAEs): SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 | Number of Participants With Serious Adverse Events (SAEs): SAD Cohort | 0 Participants |
| SAD: Placebo (Japanese Participants) | Number of Participants With Serious Adverse Events (SAEs): SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 (Japanese Participants) | Number of Participants With Serious Adverse Events (SAEs): SAD Cohort | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs): MD Cohort
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the last follow-up date, were considered as TEAEs. AEs included all SAEs and Non-SAEs.
Time frame: From start of study intervention (Day 1) up to end of study, approximately of 15.5 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs): MD Cohort | 2 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): MD Cohort | 5 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the last follow-up date, were considered as TEAEs. AEs included all SAEs and Non-SAEs.
Time frame: From start of study intervention (Day 1) up to end of study, approximately up to 15 months
Population: Safety analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort | 4 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort | 1 Participants |
| SAD: PF-07261271 Dose Level 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort | 1 Participants |
| SAD: PF-07261271 Dose Level 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort | 3 Participants |
| SAD: PF-07261271 Dose Level 4 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort | 2 Participants |
| SAD: Placebo (Japanese Participants) | Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort | 0 Participants |
| SAD: PF-07261271 Dose Level 4 (Japanese Participants) | Number of Participants With Treatment Emergent Adverse Events (TEAEs): SAD Cohort | 1 Participants |
Secondary
Area Under the Concentration Time Profile From Time Zero to Time Tau (τ), the Dosing Interval (AUCtau) of PF-07261271: MD Cohort
AUCtau was defined as area under the concentration time profile from time zero to time tau (τ), the dosing interval, where tau=672 hours for every 4-week dosing. AUCtau was determined by Linear Log trapezoidal method.
Time frame: Predose and 0, 2, 4, 8, 12, 48, 96, 192, 360, 720, 744, 1224, 1584, 1944, 2664, 4104, 4824, 5544, 6264, 6984, 7704, 8424, 9144 and 11304 hours post-dose on Day 1 and 29
Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAD: Placebo | Area Under the Concentration Time Profile From Time Zero to Time Tau (τ), the Dosing Interval (AUCtau) of PF-07261271: MD Cohort | Day 1 | 17600000 Nanograms*hour per milliliter | Geometric Coefficient of Variation 27 |
| SAD: Placebo | Area Under the Concentration Time Profile From Time Zero to Time Tau (τ), the Dosing Interval (AUCtau) of PF-07261271: MD Cohort | Day 29 | 27900000 Nanograms*hour per milliliter | Geometric Coefficient of Variation 22 |
Secondary
Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Time Point (AUClast) of PF-07261271: SAD Cohort
AUClast was determined using Linear Log trapezoidal method.
Time frame: Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose
Population: Pharmacokinetic (PK) parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD: Placebo | Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Time Point (AUClast) of PF-07261271: SAD Cohort | NA Nanograms*hour per milliliter | — |
| SAD: PF-07261271 Dose Level 1 | Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Time Point (AUClast) of PF-07261271: SAD Cohort | NA Nanograms*hour per milliliter | — |
| SAD: PF-07261271 Dose Level 2 | Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Time Point (AUClast) of PF-07261271: SAD Cohort | 65600000 Nanograms*hour per milliliter | Geometric Coefficient of Variation 35 |
| SAD: PF-07261271 Dose Level 3 | Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Time Point (AUClast) of PF-07261271: SAD Cohort | 324100000 Nanograms*hour per milliliter | Geometric Coefficient of Variation 18 |
| SAD: PF-07261271 Dose Level 4 | Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Time Point (AUClast) of PF-07261271: SAD Cohort | 345000000 Nanograms*hour per milliliter | Geometric Coefficient of Variation 28 |
Secondary
Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07261271: SAD Cohort
AUCinf was determined as AUClast + (Clast\*/kel), where Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time frame: Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose
Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD: Placebo | Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07261271: SAD Cohort | NA Nanograms*hour per milliliter | — |
| SAD: PF-07261271 Dose Level 1 | Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07261271: SAD Cohort | NA Nanograms*hour per milliliter | — |
| SAD: PF-07261271 Dose Level 2 | Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07261271: SAD Cohort | 61010000 Nanograms*hour per milliliter | Geometric Coefficient of Variation 36 |
| SAD: PF-07261271 Dose Level 3 | Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07261271: SAD Cohort | 332600000 Nanograms*hour per milliliter | Geometric Coefficient of Variation 18 |
| SAD: PF-07261271 Dose Level 4 | Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07261271: SAD Cohort | 368100000 Nanograms*hour per milliliter | Geometric Coefficient of Variation 28 |
Secondary
Cmax of PF-07261271: MD Cohort
Cmax was defined as maximum serum concentration.
Time frame: Predose and 0, 2, 4, 8, 12, 48, 96, 192, 360, 720, 744, 1224, 1584, 1944, 2664, 4104, 4824, 5544, 6264, 6984, 7704, 8424, 9144 and 11304 hours post-dose on Day 1 and 29
Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAD: Placebo | Cmax of PF-07261271: MD Cohort | Day 1 | 34120 Nanograms*hour per milliliter | Geometric Coefficient of Variation 28 |
| SAD: Placebo | Cmax of PF-07261271: MD Cohort | Day 29 | 49600 Nanograms*hour per milliliter | Geometric Coefficient of Variation 28 |
Secondary
Maximum Plasma Concentration (Cmax) of PF-07261271: SAD Cohort
Cmax was defined as maximum serum concentration.
Time frame: Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose
Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD: Placebo | Maximum Plasma Concentration (Cmax) of PF-07261271: SAD Cohort | NA Nanograms per milliliter | — |
| SAD: PF-07261271 Dose Level 1 | Maximum Plasma Concentration (Cmax) of PF-07261271: SAD Cohort | NA Nanograms per milliliter | — |
| SAD: PF-07261271 Dose Level 2 | Maximum Plasma Concentration (Cmax) of PF-07261271: SAD Cohort | 143300 Nanograms per milliliter | Geometric Coefficient of Variation 21 |
| SAD: PF-07261271 Dose Level 3 | Maximum Plasma Concentration (Cmax) of PF-07261271: SAD Cohort | 372800 Nanograms per milliliter | Geometric Coefficient of Variation 17 |
| SAD: PF-07261271 Dose Level 4 | Maximum Plasma Concentration (Cmax) of PF-07261271: SAD Cohort | 313900 Nanograms per milliliter | Geometric Coefficient of Variation 31 |
Secondary
Number of Participants With ADA Against PF-07261271: MD Cohort
ADA positive defined as ADA titer \>= 100; ADA negative defined as ADA titer \< 100. Baseline was defined as the last pre-dose measurement.
Time frame: Baseline up to 15.5 months
Population: Immunogenicity data analysis was performed on the safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With ADA Against PF-07261271: MD Cohort | 6 Participants |
Secondary
Number of Participants With Anti-drug Antibodies (ADA) Against PF-07261271: SAD Cohort
ADA positive was defined as ADA titer \>= 100; ADA negative defined as ADA titer \< 100. Baseline was defined as the last pre-dose measurement
Time frame: Baseline up to 15 months
Population: Immunogenicity data analysis was performed on the safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Anti-drug Antibodies (ADA) Against PF-07261271: SAD Cohort | 2 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Anti-drug Antibodies (ADA) Against PF-07261271: SAD Cohort | 2 Participants |
| SAD: PF-07261271 Dose Level 2 | Number of Participants With Anti-drug Antibodies (ADA) Against PF-07261271: SAD Cohort | 4 Participants |
| SAD: PF-07261271 Dose Level 3 | Number of Participants With Anti-drug Antibodies (ADA) Against PF-07261271: SAD Cohort | 6 Participants |
| SAD: PF-07261271 Dose Level 4 | Number of Participants With Anti-drug Antibodies (ADA) Against PF-07261271: SAD Cohort | 4 Participants |
Secondary
Number of Participants With NAb Against PF-07261271: MD Cohort
NAb was determined by electrochemiluminescent (ECL) competitive ligand binding assay using the Meso Scale Discovery (MSD) platform.
Time frame: Baseline up to 15.5 months
Population: Immunogenicity data analysis was performed on the safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With NAb Against PF-07261271: MD Cohort | 5 Participants |
Secondary
Number of Participants With Neutralizing Antibodies (NAb) Against PF-07261271: SAD Cohort
NAb was determined by electrochemiluminescent (ECL) competitive ligand binding assay using the Meso Scale Discovery (MSD) platform.
Time frame: Baseline up to 15 months
Population: Immunogenicity data analysis was performed on the safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: Placebo | Number of Participants With Neutralizing Antibodies (NAb) Against PF-07261271: SAD Cohort | 2 Participants |
| SAD: PF-07261271 Dose Level 1 | Number of Participants With Neutralizing Antibodies (NAb) Against PF-07261271: SAD Cohort | 2 Participants |
| SAD: PF-07261271 Dose Level 2 | Number of Participants With Neutralizing Antibodies (NAb) Against PF-07261271: SAD Cohort | 4 Participants |
| SAD: PF-07261271 Dose Level 3 | Number of Participants With Neutralizing Antibodies (NAb) Against PF-07261271: SAD Cohort | 5 Participants |
| SAD: PF-07261271 Dose Level 4 | Number of Participants With Neutralizing Antibodies (NAb) Against PF-07261271: SAD Cohort | 2 Participants |
Secondary
Terminal Elimination Half-life (t1/2) of PF-07261271: MD Cohort
t1/2 was determined using Loge (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear -concentration time- curve.
Time frame: Predose and 0, 2, 4, 8, 12, 48, 96, 192, 360, 720, 744, 1224, 1584, 1944, 2664, 4104, 4824, 5544, 6264, 6984, 7704, 8424, 9144 and 11304 hours post-dose on Day 1 and 29
Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD: Placebo | Terminal Elimination Half-life (t1/2) of PF-07261271: MD Cohort | 1150 Hours | Standard Deviation 856.4 |
Secondary
Terminal Elimination Half-life (t1/2) of PF-07261271: SAD Cohort
t1/2 was determined using Loge (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear -concentration time- curve.
Time frame: Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose
Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD: Placebo | Terminal Elimination Half-life (t1/2) of PF-07261271: SAD Cohort | NA Hours | — |
| SAD: PF-07261271 Dose Level 1 | Terminal Elimination Half-life (t1/2) of PF-07261271: SAD Cohort | NA Hours | — |
| SAD: PF-07261271 Dose Level 2 | Terminal Elimination Half-life (t1/2) of PF-07261271: SAD Cohort | 330.7 Hours | Standard Deviation 193.29 |
| SAD: PF-07261271 Dose Level 3 | Terminal Elimination Half-life (t1/2) of PF-07261271: SAD Cohort | 1533 Hours | Standard Deviation 324.39 |
| SAD: PF-07261271 Dose Level 4 | Terminal Elimination Half-life (t1/2) of PF-07261271: SAD Cohort | 1529 Hours | Standard Deviation 1018.5 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of PF-07261271: SAD Cohort
Tmax was defined as time for Cmax.
Time frame: Predose and 0, 2, 4, 8, 12, 24, 48, 72, 192, 360, 768, 1104, 1464, 2184, 4344, 5064, 5784, 6504, 7224, 7944, 8664, 10824 hours post dose
Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SAD: Placebo | Time to Maximum Plasma Concentration (Tmax) of PF-07261271: SAD Cohort | NA Hours |
| SAD: PF-07261271 Dose Level 1 | Time to Maximum Plasma Concentration (Tmax) of PF-07261271: SAD Cohort | NA Hours |
| SAD: PF-07261271 Dose Level 2 | Time to Maximum Plasma Concentration (Tmax) of PF-07261271: SAD Cohort | 2.12 Hours |
| SAD: PF-07261271 Dose Level 3 | Time to Maximum Plasma Concentration (Tmax) of PF-07261271: SAD Cohort | 3.13 Hours |
| SAD: PF-07261271 Dose Level 4 | Time to Maximum Plasma Concentration (Tmax) of PF-07261271: SAD Cohort | 5.26 Hours |
Secondary
Tmax of PF-07261271: MD Cohort
Tmax was defined as time for Cmax.
Time frame: Predose and 0, 2, 4, 8, 12, 48, 96, 192, 360, 720, 744, 1224, 1584, 1944, 2664, 4104, 4824, 5544, 6264, 6984, 7704, 8424, 9144 and 11304 hours post-dose on Day 1 and 29
Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-07261271 and who had at least 1 of the PK parameters of interest calculated. Here, 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SAD: Placebo | Tmax of PF-07261271: MD Cohort | Day 1 | 253 Hours |
| SAD: Placebo | Tmax of PF-07261271: MD Cohort | Day 29 | 170 Hours |