Diabetes Mellitus, Type 1
Conditions
Keywords
Phase 1, RN168, Adults, Type 1 Diabetes, T1D
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of multiple doses of PF-06342674. Several dose levels will be evaluated.
Interventions
DRUGPlacebo
Placebo
BIOLOGICALPF-06342674 Dose A
Multiple SC Doses
BIOLOGICALPF-06342674 Dose B
Multiple SC Doses
BIOLOGICALPF-06342674 Dose C
Multiple SC Doses
BIOLOGICALPF-06342674 Dose D
Multiple SC Doses
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women and men age 18 and older. * Diagnosis of type 1 diabetes within 2 years of randomization. * Peak stimulated C-peptide levels ≥ 0.15 ng/mL.
Exclusion criteria
* Anticipated ongoing use of diabetes medications other than insulin. * Evidence or history of diabetic complications with significant end-organ damage. * Episode of severe hypoglycemia within 60 days of randomization. * Multiple hospitalizations for diabetic ketoacidosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1, Day 15, Day 29, Day 57, Day 85, and Day127 and follow-up visits | Number of participants with serum anti-PF-06342674 antibody response to the intramuscular tetanus vaccine was reported. Positive Anti-PF-06342674 Antibody response is defined as anti-tetanus toxoid immunoglobulin G (IgG) titer value \>=100 |
| Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Day 1 through Day 127 | Any blood glucose values \<55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Day 1 through Day 127 | The following laboratory test parameters were evaluated in this study: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),coagulation (partial thromboplastin time, prothrombin, and prothrombin international ratio), liver function(total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose, glycosylated, and hemoglobin), and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, urobilinogen, qualitative bilirubin, nitrites, leukocyte, esterase and microscopy). |
| Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Day 1 through Day 127 | Number of participants with vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: SBP \<90 millimeter of mercury(mmHg); Criterion B: DBP \<50 mmHg; Criterion C: pulse rate \< 40 beats per minute(BPM); Criterion D: pulse rate \>120 BPM |
| Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Day 1 through Day 127 | The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in systolic BP \>= 30 mmHg; Criterion B: maximum decrease from baseline in diastolic BP \>=20 mmHg |
| Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Day 1 through Day 127 | The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in systolic BP \>= 30 mmHg; Criterion B: maximum increase from baseline in diastolic BP \>= 20 mmHg |
| Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Day 1 through Day 127 | The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) \>=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) \>=200 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-\<480 msec; Criterion D: maximum QTcF interval 480-\<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) \>=500 msec |
| Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Day 1 through Day 127 | Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)\>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg \>= 25/50%; Criterion C: maximum QTcF interval increase from baseline 30\<=change\<60 msec; Criterion D: maximum QTcF interval increase from baseline change \>=60 msec. |
| Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) | Day 1 through Day 127 | Number of participants with dose limiting or intolerable treatment related adverse events (AEs) was reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. |
| Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) | Day 1 through Day 127 | Number of participants with all-causality treatment emergent adverse events were reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. TEAEs included both serious and non-serious AE |
| Number of Participants With Treatment-Related TEAEs | Day 1 through Day 127 | Number of participants with treatment-related TEAEs were reported. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. |
| Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Day 1 through Day 127 | TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE. |
| Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events | Day 1 through Day 127 | Number of participants with all-causality treatment-emergent hypoglycemic adverse events was reported. Any blood glucose values less than(\<)55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Oral Clearance (CL/F) on Day 71 | 0,1,4 hours post-dose on Day 71 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. On Day 71, 6 participants in cohort 1 had reportable CL/F values |
| Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | 0, 1, 4 hours post-dose on Day 1 and Day 71 | Maximum serum concentration was observed directly from data on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Cmax values |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | 0, 1, 4 hours post-dose on Day 1 and Day 71 | Time to reach maximum observed plasma concentration was observed directly from data as time of first occurrence on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Tmax values |
| Plasma Decay Half-Life (t1/2) on Day 71 | 0, 1, 4 hours post-dose on Day 71 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. On Day 71, 2 participants in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable values for t1/2 |
| Apparent Volume of Distribution (Vz/F) on Day 71 | 0, 1, 4 hours post-dose on Day 71 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. On Day 71, 1 participant in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable Vz/F values |
| Accumulation Ratio (Rac) on Day 71 | 0, 1, 4, hours post-dose on Day 71 | Accumulation ratio was calculated from AUCinf at last dose/AUCinf at first dose, where AUCinf is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). On Day 71, 3 participants in cohort 1 had reportable Rac values. |
| Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | 0,1,4 hours post-dose on Day 1 and Day 71 | Area under the concentration-time profile from time 0 to time tau (τ), the dosing interval, where tau = 168 hours for once a week dosing; tau = 336 hours for once every 2 weeks dosing. On Day 1, 3 participants in cohort 1 had reportable AUCtau values. On Day 71, 6 participants in cohort 1 and 2 participants in cohort 4 had reportable AUCtau values |
Countries
United States
Participant flow
Pre-assignment details
A total of 37 participants were assigned to study treatment (placebo: 7 subjects; PF-06342674: 30 subjects)
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | 7 |
| PF-06342674 1 mg/kg Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | 8 |
| PF-06342674 3 mg/kg Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | 9 |
| PF-06342674 6 mg/kg Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | 5 |
| PF-06342674 8 mg/kg Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | 8 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | PF-06342674 1 mg/kg | PF-06342674 3 mg/kg | PF-06342674 6 mg/kg | PF-06342674 8 mg/kg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 33.9 years STANDARD_DEVIATION 11.1 | 25.6 years STANDARD_DEVIATION 8.5 | 37.8 years STANDARD_DEVIATION 15.8 | 29 years STANDARD_DEVIATION 12.3 | 30.8 years STANDARD_DEVIATION 7.7 | 31.7 years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 6 Participants | 0 Participants | 4 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 22 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 6 / 8 | 6 / 9 | 4 / 5 | 5 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 | 1 / 9 | 0 / 5 | 0 / 8 |
Outcome results
Primary
Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade
TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 2 | 2 participants |
| Placebo | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 4 | 0 participants |
| Placebo | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 1 | 3 participants |
| Placebo | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 3 | 2 participants |
| Placebo | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 5 | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 3 | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 4 | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 5 | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 2 | 6 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 1 | 2 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 1 | 1 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 2 | 4 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 3 | 2 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 4 | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 5 | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 4 | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 3 | 2 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 1 | 3 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 5 | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 2 | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 3 | 1 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 4 | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 5 | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 2 | 4 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 1 | 1 participants |
Primary
Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs)
Number of participants with all-causality treatment emergent adverse events were reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. TEAEs included both serious and non-serious AE
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) | 7 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) | 8 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) | 7 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) | 5 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) | 6 participants |
Primary
Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events
Number of participants with all-causality treatment-emergent hypoglycemic adverse events was reported. Any blood glucose values less than(\<)55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia.
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events | 4 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events | 4 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events | 5 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events | 1 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events | 3 participants |
Primary
Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade
Any blood glucose values \<55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 4 | 0 participants |
| Placebo | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 1 | 1 participants |
| Placebo | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 5 | 0 participants |
| Placebo | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 2 | 1 participants |
| Placebo | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 3 | 2 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 4 | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 3 | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 2 | 4 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 5 | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 1 | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 3 | 1 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 1 | 1 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 2 | 3 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 4 | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 5 | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 5 | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 1 | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 4 | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 3 | 1 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 2 | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 3 | 1 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 4 | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 1 | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 5 | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade | Grade 2 | 2 participants |
Primary
Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs)
Number of participants with dose limiting or intolerable treatment related adverse events (AEs) was reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) | 1 participants |
Primary
Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value)
The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) \>=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) \>=200 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-\<480 msec; Criterion D: maximum QTcF interval 480-\<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) \>=500 msec
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion D | 0 participants |
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion A | 0 participants |
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion E | 0 participants |
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion B | 0 participants |
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion C | 1 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion D | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion C | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion B | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion E | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion A | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion C | 3 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion A | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion B | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion D | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion E | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion E | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion A | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion D | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion C | 1 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion B | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion C | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion D | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion A | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion E | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) | Criterion B | 0 participants |
Primary
Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline)
Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)\>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg \>= 25/50%; Criterion C: maximum QTcF interval increase from baseline 30\<=change\<60 msec; Criterion D: maximum QTcF interval increase from baseline change \>=60 msec.
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion C | 1 participants |
| Placebo | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion D | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion D | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion C | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion D | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion C | 2 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion D | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion C | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion D | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion C | 1 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
The following laboratory test parameters were evaluated in this study: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),coagulation (partial thromboplastin time, prothrombin, and prothrombin international ratio), liver function(total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose, glycosylated, and hemoglobin), and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, urobilinogen, qualitative bilirubin, nitrites, leukocyte, esterase and microscopy).
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 7 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 7 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 8 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 5 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 7 participants |
Primary
Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit
Number of participants with serum anti-PF-06342674 antibody response to the intramuscular tetanus vaccine was reported. Positive Anti-PF-06342674 Antibody response is defined as anti-tetanus toxoid immunoglobulin G (IgG) titer value \>=100
Time frame: Day 1, Day 15, Day 29, Day 57, Day 85, and Day127 and follow-up visits
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Positive | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Positive | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Negative | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Positive | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Negative | 2 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Positive | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Negative | 2 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Positive | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Positive | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Negative | 1 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Negative | 2 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Negative | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Negative | 1 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Negative | 1 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Negative | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Positive | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Positive | 0 participants |
| Placebo | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Positive | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Positive | 2 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Negative | 2 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Negative | 3 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Positive | 1 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Positive | 5 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Positive | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Negative | 3 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Negative | 6 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Positive | 4 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Negative | 1 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Positive | 4 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Negative | 4 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Positive | 4 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Negative | 8 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Negative | 1 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Negative | 4 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Positive | 1 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Positive | 6 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Positive | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Negative | 9 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Negative | 6 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Positive | 2 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Negative | 6 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Positive | 2 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Negative | 4 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Positive | 4 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Negative | 4 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Positive | 3 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Negative | 5 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Positive | 2 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Negative | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Positive | 3 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Negative | 1 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Positive | 1 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Negative | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Positive | 1 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Negative | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Negative | 3 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Negative | 4 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Positive | 5 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Positive | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Negative | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Positive | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Negative | 5 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Positive | 5 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Negative | 5 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Negative | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Positive | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Positive | 5 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Negative | 5 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Negative | 1 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Positive | 4 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Positive | 2 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Positive | 1 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Negative | 4 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Negative | 7 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 57 Positive | 1 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Negative | 3 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Negative | 8 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Positive | 6 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 29 Positive | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Negative | 8 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Negative | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up3 Positive | 1 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Negative | 2 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Positive | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 127 Negative | 2 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up2 Positive | 1 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 85 Positive | 4 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Follow-up1 Positive | 5 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 15 Negative | 8 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit | Day 1 Positive | 0 participants |
Primary
Number of Participants With Treatment-Related TEAEs
Number of participants with treatment-related TEAEs were reported. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug.
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Related TEAEs | 5 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Treatment-Related TEAEs | 6 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Treatment-Related TEAEs | 6 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Treatment-Related TEAEs | 4 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Treatment-Related TEAEs | 5 participants |
Primary
Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values)
Number of participants with vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: SBP \<90 millimeter of mercury(mmHg); Criterion B: DBP \<50 mmHg; Criterion C: pulse rate \< 40 beats per minute(BPM); Criterion D: pulse rate \>120 BPM
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion A | 0 participants |
| Placebo | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion B | 1 participants |
| Placebo | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion C | 1 participants |
| Placebo | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion D | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion A | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion D | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion B | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion C | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion D | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion B | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion C | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion A | 1 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion A | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion B | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion D | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion C | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion D | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion C | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion B | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) | Criterion A | 0 participants |
Primary
Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline)
The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in systolic BP \>= 30 mmHg; Criterion B: maximum decrease from baseline in diastolic BP \>=20 mmHg
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion A | 0 participants |
| Placebo | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion B | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion A | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion B | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion A | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion B | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion B | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion A | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion A | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) | Criterion B | 1 participants |
Primary
Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline)
The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in systolic BP \>= 30 mmHg; Criterion B: maximum increase from baseline in diastolic BP \>= 20 mmHg
Time frame: Day 1 through Day 127
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 1 participants |
| Placebo | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
| Cohort 1 PF-06342674 1 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
| Cohort 2 PF-06342674 3 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 1 participants |
| Cohort 4 PF-06342674 6 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion A | 0 participants |
| Cohort 3 PF-06342674 8 mg/kg | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) | Criterion B | 0 participants |
Secondary
Accumulation Ratio (Rac) on Day 71
Accumulation ratio was calculated from AUCinf at last dose/AUCinf at first dose, where AUCinf is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). On Day 71, 3 participants in cohort 1 had reportable Rac values.
Time frame: 0, 1, 4, hours post-dose on Day 71
Population: All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. On Day 71, 3 participants in cohort 1 had reportable Rac values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Accumulation Ratio (Rac) on Day 71 | 1.115 Ratio | Geometric Coefficient of Variation 48 |
| Cohort 1 PF-06342674 1 mg/kg | Accumulation Ratio (Rac) on Day 71 | 1.532 Ratio | Geometric Coefficient of Variation 28 |
| Cohort 2 PF-06342674 3 mg/kg | Accumulation Ratio (Rac) on Day 71 | NA Ratio | — |
| Cohort 4 PF-06342674 6 mg/kg | Accumulation Ratio (Rac) on Day 71 | 1.355 Ratio | Geometric Coefficient of Variation 19 |
Secondary
Apparent Oral Clearance (CL/F) on Day 71
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. On Day 71, 6 participants in cohort 1 had reportable CL/F values
Time frame: 0,1,4 hours post-dose on Day 71
Population: All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. Day 71, 6 participants in cohort 1 had reportable CL/F values
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Oral Clearance (CL/F) on Day 71 | 2.340 mL/hr/kg | Geometric Coefficient of Variation 58 |
| Cohort 1 PF-06342674 1 mg/kg | Apparent Oral Clearance (CL/F) on Day 71 | 1.477 mL/hr/kg | Geometric Coefficient of Variation 29 |
| Cohort 2 PF-06342674 3 mg/kg | Apparent Oral Clearance (CL/F) on Day 71 | NA mL/hr/kg | — |
| Cohort 4 PF-06342674 6 mg/kg | Apparent Oral Clearance (CL/F) on Day 71 | 1.017 mL/hr/kg | Geometric Coefficient of Variation 42 |
Secondary
Apparent Volume of Distribution (Vz/F) on Day 71
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. On Day 71, 1 participant in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable Vz/F values
Time frame: 0, 1, 4 hours post-dose on Day 71
Population: All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. On Day 71, 1 participant in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable Vz/F values
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Volume of Distribution (Vz/F) on Day 71 | NA mL/kg | — |
| Cohort 1 PF-06342674 1 mg/kg | Apparent Volume of Distribution (Vz/F) on Day 71 | 141.2 mL/kg | Geometric Coefficient of Variation 18 |
| Cohort 2 PF-06342674 3 mg/kg | Apparent Volume of Distribution (Vz/F) on Day 71 | NA mL/kg | — |
| Cohort 4 PF-06342674 6 mg/kg | Apparent Volume of Distribution (Vz/F) on Day 71 | 129.5 mL/kg | Geometric Coefficient of Variation 18 |
Secondary
Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71
Area under the concentration-time profile from time 0 to time tau (τ), the dosing interval, where tau = 168 hours for once a week dosing; tau = 336 hours for once every 2 weeks dosing. On Day 1, 3 participants in cohort 1 had reportable AUCtau values. On Day 71, 6 participants in cohort 1 and 2 participants in cohort 4 had reportable AUCtau values
Time frame: 0,1,4 hours post-dose on Day 1 and Day 71
Population: All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. On Day 1, 3 participants in cohort 1 had reportable AUCtau values. On Day 71, 6 participants in cohort 1 and 2 participants in cohort 4 had reportable AUCtau values
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | Day 1 | 384900 ng*hr/mL | Geometric Coefficient of Variation 43 |
| Placebo | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | Day 71 | 426700 ng*hr/mL | Geometric Coefficient of Variation 58 |
| Cohort 1 PF-06342674 1 mg/kg | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | Day 71 | 2029000 ng*hr/mL | Geometric Coefficient of Variation 29 |
| Cohort 1 PF-06342674 1 mg/kg | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | Day 1 | 1323000 ng*hr/mL | Geometric Coefficient of Variation 43 |
| Cohort 2 PF-06342674 3 mg/kg | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | Day 1 | 2570000 ng*hr/mL | Geometric Coefficient of Variation 31 |
| Cohort 2 PF-06342674 3 mg/kg | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | Day 71 | NA ng*hr/mL | — |
| Cohort 4 PF-06342674 6 mg/kg | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | Day 1 | 5805000 ng*hr/mL | Geometric Coefficient of Variation 28 |
| Cohort 4 PF-06342674 6 mg/kg | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 | Day 71 | 7869000 ng*hr/mL | Geometric Coefficient of Variation 42 |
Secondary
Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71
Maximum serum concentration was observed directly from data on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Cmax values
Time frame: 0, 1, 4 hours post-dose on Day 1 and Day 71
Population: All enrolled participants treated who had at least 1 concentration value. On Day 71, 2 participants in cohort 4 had reportable Cmax values
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | Day 1 | 2114 ng/mL | Geometric Coefficient of Variation 83 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | Day 71 | 2612 ng/mL | Geometric Coefficient of Variation 89 |
| Cohort 1 PF-06342674 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | Day 71 | 10600 ng/mL | Geometric Coefficient of Variation 22 |
| Cohort 1 PF-06342674 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | Day 1 | 8512 ng/mL | Geometric Coefficient of Variation 42 |
| Cohort 2 PF-06342674 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | Day 71 | NA ng/mL | — |
| Cohort 2 PF-06342674 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | Day 1 | 20890 ng/mL | Geometric Coefficient of Variation 29 |
| Cohort 4 PF-06342674 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | Day 1 | 31610 ng/mL | Geometric Coefficient of Variation 27 |
| Cohort 4 PF-06342674 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 | Day 71 | 39870 ng/mL | Geometric Coefficient of Variation 34 |
Secondary
Plasma Decay Half-Life (t1/2) on Day 71
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. On Day 71, 2 participants in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable values for t1/2
Time frame: 0, 1, 4 hours post-dose on Day 71
Population: All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. On Day 71, 2 participants in cohort 1 , 5 participants in cohort 2, and 7 participants in cohort 3 had reportable values for t1/2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Decay Half-Life (t1/2) on Day 71 | NA hr | — |
| Cohort 1 PF-06342674 1 mg/kg | Plasma Decay Half-Life (t1/2) on Day 71 | 64.62 hr | Standard Deviation 7.34 |
| Cohort 2 PF-06342674 3 mg/kg | Plasma Decay Half-Life (t1/2) on Day 71 | NA hr | — |
| Cohort 4 PF-06342674 6 mg/kg | Plasma Decay Half-Life (t1/2) on Day 71 | 85.54 hr | Standard Deviation 23.54 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71
Time to reach maximum observed plasma concentration was observed directly from data as time of first occurrence on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Tmax values
Time frame: 0, 1, 4 hours post-dose on Day 1 and Day 71
Population: All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed.On Day 71, 2 participants in cohort 4 had reportable Tmax values
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | Day 1 | 48.8 hr | Full Range 83 |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | Day 71 | 48.9 hr | Full Range 89 |
| Cohort 1 PF-06342674 1 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | Day 71 | 60.2 hr | Full Range 22 |
| Cohort 1 PF-06342674 1 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | Day 1 | 48.9 hr | Full Range 42 |
| Cohort 2 PF-06342674 3 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | Day 1 | 48.1 hr | Full Range 29 |
| Cohort 2 PF-06342674 3 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | Day 71 | NA hr | — |
| Cohort 4 PF-06342674 6 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | Day 71 | 86.3 hr | Full Range 34 |
| Cohort 4 PF-06342674 6 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 | Day 1 | 51.8 hr | Full Range 27 |