Type 2 Diabetes Mellitus
Conditions
Keywords
first in human, single dose, multiple dose, escalation, safety study, Type 2 Diabetes Mellitus
Brief summary
A first in human study to determine the safety, tolerability and pharmacokinetics of single and multiple ascending doses of PF-06293620 in subjects with Type 2 Diabetes Mellitus
Interventions
BIOLOGICALPF-06293620
subcutaneous, single dose 0.3 mg/kg
BIOLOGICALPlacebo
Subcutaneous normal saline single dose
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Men and women of non-childbearing potential with Type 2 Diabetes Mellitus * Subjects on stable doses of metformin \>/= 1500 mg daily (SAD cohorts) or \>/= 1000 mg daily (MAD cohorts) x 30 days prior to screening * HbA1c 7-10% (SAD Cohorts) or 6.5-10% (MAD cohorts) inclusive at screening * Fasting C-peptide \>1.12 ng/mL (SAD cohorts) or \>/= 0.8 mg/mL (MAD cohorts) at screening
Exclusion criteria
* History of Type 1 diabetes mellitus * Evidence of diabetic complications with significant end-organ damage * History of chronic pancreatitis or at high risk for pancreatitis * Poorly controlled hypertension * History of cardiovascular or cerebrovascular event or procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Days 1 to 85 for SAD cohorts and Days 1 to 169 for MAD cohorts; participants with positive anti-drug antibody (ADA) results were followed up to stabilization of ADA titers or up to 9 months after Day 169 visit. | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to Day 85 (for SAD cohorts) or Day 169 (for MAD cohorts) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs. Causality with the study treatment was determined by the investigator. |
| Number of Participants With Dose Limiting or Intolerable Adverse Events | Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts | Dose limiting or intolerable AEs were originally planned to be collected. However, this outcome measure was not actually summarized, since collection and monitoring of treatment-emergent AEs was performed during the study, and deemed sufficient to ensure the participants safety. |
| Number of Participants With Positive Anti-drug Antibody (ADA) Result | Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts | ADA against PF-06293620 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer \>=1.88 was considered positive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Clearance (CL/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration | Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | Apparent clearance (CL/F) of PF-06293620 was calculated as dose/AUCtau, where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours). |
| Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | AUClast(dn) of PF-06293620 was calculated as AUClast/dose, where AUClast was area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration. |
| Clearance (CL) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms. |
| Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | Apparent Clearance (CL/F) of PF-06293620 was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arms. |
| Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | Maximum serum concentration (Cmax) of PF-06293620 was observed directly from data. |
| Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | Time for Maximum serum concentration (Tmax) of PF-06293620 was observed directly from data as time of first occurrence. |
| Steady-state Volume of Distribution (Vss) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | Steady-state volume of distribution (Vss) of PF-06293620 was calculated as CL\*MRT, where MRT was the mean residence time calculated as (AUMCinf/AUCinf - infusion duration/2), AUMCinf was area under the moment curve from time 0 extrapolated to infinity; CL was the clearance. This outcome measure only applies to IV arms. |
| Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | Apparent Volume of Distribution (Vz/F) of PF-06293620 was calculated as dose/(AUCinf\*kel), where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time, kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. This outcome measure only applies to SC arms. |
| Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | Terminal elimination half-life (Thalf) of PF-06293620 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. |
| Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | AUCinf was calculated as AUClast +(Clast\*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. |
| Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | — |
| Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | Average Concentration (Cav) of PF-06293620 was calculated as AUCtau/tau, where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours). |
| Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06293620 (MAD Cohorts) After Day 57 Administration | Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | — |
| Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | Time for maximum serum concentration (Tmax) of PF-06293620 was observed directly from data as time of first occurrence. |
| Apparent Volume of Distribution (Vz/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration | Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | Apparent volume of distribution (Vz/F) of PF-06293620 was calculated as dose/(AUCtau/kel), where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours); and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. |
| Terminal Elimination Half-life (Thalf) of PF-06293620 (MAD Cohorts) After Day 57 Administration | Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | Terminal elimination half-life (Thalf) of PF-06293620 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. |
| Observed Accumulation Ratio Based on AUC (Rac) of PF-06293620 (MAD Cohorts) | Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | Observed accumulation ratio based on AUC (Rac) of PF-06293620 was calculated as AUCtau(Day57)/AUCtau(Day1). |
| Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of PF-06293620 (MAD Cohorts) | Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | Observed accumulation ratio based on Cmax (Rac,Cmax) of PF-06293620 was calculated as Cmax(Day57)/Cmax(Day1). |
| Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169 | Tau refers to the dosing interval, which was 4 weeks (672 hours). Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method. |
| Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | AUCinf(dn) was calculated as AUCinf/dose, where AUCinf is area under the serum concentration-time profile from time 0 extrapolated to infinite time. |
| Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts) | Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85 | Area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of PF-06293620 was determined using linear/log trapezoidal method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo SC (SAD Cohorts) One group of participants in the single-ascending dose (SAD) cohorts received a single dose of placebo matched to PF-06293620 by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 9 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) One group of participants in the single-ascending dose (SAD) cohorts received a single dose of PF-06293620 at 0.3 mg/kg by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 6 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) One group of participants in the single-ascending dose (SAD) cohorts received a single dose of PF-06293620 at 1.0 mg/kg by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 6 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) One group of participants in the single-ascending dose (SAD) cohorts received a single dose of PF-06293620 at 3.0 mg/kg by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 6 |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) One group of participants in the single-ascending dose (SAD) cohorts received a single dose of PF-06293620 at 6.0 mg/kg by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 9 |
| Placebo IV (SAD Cohorts) One group of participants in the single-ascending dose (SAD) cohorts received a single dose of placebo matched to PF-06293620 by intravenous (IV) infusion over approximately 60 minutes following an overnight fast of at least 10 hours. | 2 |
| PF-06293620 1.0 mg/kg IV (SAD Cohorts) One group of participants in the single-ascending dose (SAD) cohorts received a single dose of PF-06293620 at 1.0 mg/kg by intravenous (IV) infusion over approximately 60 minutes following an overnight fast of at least 10 hours. | 6 |
| Placebo SC (MAD Cohorts) One group of participants in the multiple-ascending dose (MAD) cohorts received placebo matched to PF-06293620 every 4 weeks (on Days 1, 29 and 57, deviation of plus or minus 2 days was allowed for Day 29 and Day 57 dosing) by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 8 |
| PF-06293620 50 mg SC (MAD Cohorts) One group of participants in the multiple-ascending dose (MAD) cohorts received PF-06293620 50 mg every 4 weeks (on Days 1, 29 and 57, deviation of plus or minus 2 days was allowed for Day 29 and Day 57 dosing) by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 8 |
| PF-06293620 75 mg SC (MAD Cohorts) One group of participants in the multiple-ascending dose (MAD) cohorts received PF-06293620 75 mg every 4 weeks (on Days 1, 29 and 57, deviation of plus or minus 2 days was allowed for Day 29 and Day 57 dosing) by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 16 |
| PF-06293620 150 mg SC (MAD Cohorts) One group of participants in the multiple-ascending dose (MAD) cohorts received PF-06293620 150 mg every 4 weeks (on Days 1, 29 and 57, deviation of plus or minus 2 days was allowed for Day 29 and Day 57 dosing) by subcutaneous (SC) injection to the abdomen following an overnight fast of at least 10 hours. | 8 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo SC (SAD Cohorts) | PF-06293620 0.3 mg/kg SC (SAD Cohorts) | PF-06293620 1.0 mg/kg SC (SAD Cohorts) | PF-06293620 3.0 mg/kg SC (SAD Cohorts) | PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Placebo IV (SAD Cohorts) | PF-06293620 1.0 mg/kg IV (SAD Cohorts) | Placebo SC (MAD Cohorts) | PF-06293620 50 mg SC (MAD Cohorts) | PF-06293620 75 mg SC (MAD Cohorts) | PF-06293620 150 mg SC (MAD Cohorts) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 years | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Age, Customized <18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized 45-64 years | 7 participants | 4 participants | 4 participants | 6 participants | 6 participants | 1 participants | 5 participants | 7 participants | 4 participants | 9 participants | 8 participants | 61 participants |
| Age, Customized >=65 years | 2 participants | 2 participants | 2 participants | 0 participants | 2 participants | 0 participants | 0 participants | 1 participants | 4 participants | 7 participants | 0 participants | 20 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 5 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 7 Participants | 7 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 6 Participants | 0 Participants | 2 Participants | 6 Participants | 4 Participants | 9 Participants | 1 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 4 Participants | 3 Participants | 4 Participants | 0 Participants | 0 Participants | 4 Participants | 3 Participants | 9 Participants | 1 Participants | 34 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 2 Participants | 3 Participants | 5 Participants | 2 Participants | 6 Participants | 4 Participants | 5 Participants | 7 Participants | 7 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 2 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 16 | 0 / 8 |
| other Total, other adverse events | 5 / 9 | 3 / 6 | 3 / 6 | 5 / 6 | 5 / 9 | 0 / 2 | 3 / 6 | 4 / 8 | 4 / 8 | 11 / 16 | 7 / 8 |
| serious Total, serious adverse events | 0 / 9 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 2 | 0 / 6 | 0 / 8 | 0 / 8 | 1 / 16 | 2 / 8 |
Outcome results
Primary
Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to Day 85 (for SAD cohorts) or Day 169 (for MAD cohorts) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs. Causality with the study treatment was determined by the investigator.
Time frame: Days 1 to 85 for SAD cohorts and Days 1 to 169 for MAD cohorts; participants with positive anti-drug antibody (ADA) results were followed up to stabilization of ADA titers or up to 9 months after Day 169 visit.
Population: The safety analysis population included all participants who received any amount of dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 1 participants |
| Placebo SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| Placebo SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 5 participants |
| Placebo SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 0 participants |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 1 participants |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 0 participants |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 3 participants |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 0 participants |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 0 participants |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 3 participants |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 3 participants |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 5 participants |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 0 participants |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 3 participants |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 0 participants |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 5 participants |
| Placebo IV (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| Placebo IV (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 0 participants |
| Placebo IV (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 0 participants |
| Placebo IV (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 0 participants |
| PF-06293620 1.0 mg/kg IV (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 1 participants |
| PF-06293620 1.0 mg/kg IV (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| PF-06293620 1.0 mg/kg IV (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 3 participants |
| PF-06293620 1.0 mg/kg IV (SAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 0 participants |
| Placebo SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 0 participants |
| Placebo SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 1 participants |
| Placebo SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| Placebo SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 4 participants |
| PF-06293620 50 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 4 participants |
| PF-06293620 50 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| PF-06293620 50 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 1 participants |
| PF-06293620 50 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 0 participants |
| PF-06293620 75 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 4 participants |
| PF-06293620 75 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 1 participants |
| PF-06293620 75 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 11 participants |
| PF-06293620 75 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| PF-06293620 150 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality SAE | 2 participants |
| PF-06293620 150 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related SAE | 0 participants |
| PF-06293620 150 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | Treatment-related AE | 5 participants |
| PF-06293620 150 mg SC (MAD Cohorts) | Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events | All-causality AE | 8 participants |
Primary
Number of Participants With Dose Limiting or Intolerable Adverse Events
Dose limiting or intolerable AEs were originally planned to be collected. However, this outcome measure was not actually summarized, since collection and monitoring of treatment-emergent AEs was performed during the study, and deemed sufficient to ensure the participants safety.
Time frame: Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts
Population: Data for this outcome measure were not collected.
Primary
Number of Participants With Positive Anti-drug Antibody (ADA) Result
ADA against PF-06293620 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer \>=1.88 was considered positive.
Time frame: Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts
Population: The safety analysis population included all participants who received any amount of dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo SC (SAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 1 participants |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 5 participants |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 2 participants |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 1 participants |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 2 participants |
| Placebo IV (SAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 0 participants |
| PF-06293620 1.0 mg/kg IV (SAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 1 participants |
| Placebo SC (MAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 0 participants |
| PF-06293620 50 mg SC (MAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 5 participants |
| PF-06293620 75 mg SC (MAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 7 participants |
| PF-06293620 150 mg SC (MAD Cohorts) | Number of Participants With Positive Anti-drug Antibody (ADA) Result | 4 participants |
Secondary
Apparent Clearance (CL/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration
Apparent clearance (CL/F) of PF-06293620 was calculated as dose/AUCtau, where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours).
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Apparent Clearance (CL/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 38.19 mL/hr | Geometric Coefficient of Variation 60 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Apparent Clearance (CL/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 25.07 mL/hr | Geometric Coefficient of Variation 57 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Apparent Clearance (CL/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 24.53 mL/hr | Geometric Coefficient of Variation 47 |
Secondary
Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts)
Apparent Clearance (CL/F) of PF-06293620 was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arms.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts) | 83.20 mL/hr | — |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts) | 44.93 mL/hr | Geometric Coefficient of Variation 45 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts) | 42.05 mL/hr | Geometric Coefficient of Variation 47 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts) | 27.67 mL/hr | Geometric Coefficient of Variation 49 |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration
Apparent volume of distribution (Vz/F) of PF-06293620 was calculated as dose/(AUCtau/kel), where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours); and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Apparent Volume of Distribution (Vz/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 13.43 liters | Geometric Coefficient of Variation 38 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Apparent Volume of Distribution (Vz/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 10.45 liters | Geometric Coefficient of Variation 52 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Apparent Volume of Distribution (Vz/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 12.09 liters | Geometric Coefficient of Variation 40 |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts)
Apparent Volume of Distribution (Vz/F) of PF-06293620 was calculated as dose/(AUCinf\*kel), where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time, kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. This outcome measure only applies to SC arms.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts) | 21.10 liters | — |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts) | 16.25 liters | Geometric Coefficient of Variation 43 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts) | 20.63 liters | Geometric Coefficient of Variation 44 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts) | 18.17 liters | Geometric Coefficient of Variation 48 |
Secondary
Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration
Tau refers to the dosing interval, which was 4 weeks (672 hours). Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method.
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SC (SAD Cohorts) | Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 609.6 mcg*hr/mL | Geometric Coefficient of Variation 137 |
| Placebo SC (SAD Cohorts) | Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 1309 mcg*hr/mL | Geometric Coefficient of Variation 60 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 802.5 mcg*hr/mL | Geometric Coefficient of Variation 79 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 2991 mcg*hr/mL | Geometric Coefficient of Variation 57 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 2752 mcg*hr/mL | Geometric Coefficient of Variation 73 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 6121 mcg*hr/mL | Geometric Coefficient of Variation 48 |
Secondary
Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts)
AUCinf was calculated as AUClast +(Clast\*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts) | 300 microgram*hour/milliliter (mcg*hr/mL) | — |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts) | 1716 microgram*hour/milliliter (mcg*hr/mL) | Geometric Coefficient of Variation 46 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts) | 6306 microgram*hour/milliliter (mcg*hr/mL) | Geometric Coefficient of Variation 54 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts) | 19440 microgram*hour/milliliter (mcg*hr/mL) | Geometric Coefficient of Variation 56 |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts) | 6775 microgram*hour/milliliter (mcg*hr/mL) | Geometric Coefficient of Variation 12 |
Secondary
Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts)
Area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of PF-06293620 was determined using linear/log trapezoidal method.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts) | 128.3 mcg*hr/mL | Geometric Coefficient of Variation 54 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts) | 1619 mcg*hr/mL | Geometric Coefficient of Variation 46 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts) | 5945 mcg*hr/mL | Geometric Coefficient of Variation 53 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts) | 18080 mcg*hr/mL | Geometric Coefficient of Variation 58 |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts) | 6509 mcg*hr/mL | Geometric Coefficient of Variation 13 |
Secondary
Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration
Average Concentration (Cav) of PF-06293620 was calculated as AUCtau/tau, where AUCtau was area under the concentration-time profile from time 0 to time tau, and tau was the dosing interval, 4 weeks (672 hours).
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK concentration population included all enrolled participants treated who had at least 1 measurable concentration value.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SC (SAD Cohorts) | Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 0.9067 mcg/mL | Geometric Coefficient of Variation 137 |
| Placebo SC (SAD Cohorts) | Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 1.948 mcg/mL | Geometric Coefficient of Variation 60 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 1.194 mcg/mL | Geometric Coefficient of Variation 79 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 4.449 mcg/mL | Geometric Coefficient of Variation 57 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 4.096 mcg/mL | Geometric Coefficient of Variation 73 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 9.102 mcg/mL | Geometric Coefficient of Variation 48 |
Secondary
Clearance (CL) of PF-06293620 (SAD Cohorts)
Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Clearance (CL) of PF-06293620 (SAD Cohorts) | 14.72 mL/hr | Geometric Coefficient of Variation 16 |
Secondary
Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts)
AUCinf(dn) was calculated as AUCinf/dose, where AUCinf is area under the serum concentration-time profile from time 0 extrapolated to infinite time.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts) | 12.00 mcg*hr/mL/mg | — |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts) | 22.24 mcg*hr/mL/mg | Geometric Coefficient of Variation 45 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts) | 23.79 mcg*hr/mL/mg | Geometric Coefficient of Variation 47 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts) | 36.13 mcg*hr/mL/mg | Geometric Coefficient of Variation 49 |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts) | 67.94 mcg*hr/mL/mg | Geometric Coefficient of Variation 16 |
90% CI: [8.44, 36.95]
90% CI: [21.64, 49.51]
90% CI: [23.6, 51.95]
90% CI: [36.36, 77.78]
Secondary
Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts)
AUClast(dn) of PF-06293620 was calculated as AUClast/dose, where AUClast was area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts) | 4.779 mcg*hr/mL/mg | Geometric Coefficient of Variation 58 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts) | 21.01 mcg*hr/mL/mg | Geometric Coefficient of Variation 44 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts) | 22.47 mcg*hr/mL/mg | Geometric Coefficient of Variation 47 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts) | 33.59 mcg*hr/mL/mg | Geometric Coefficient of Variation 50 |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts) | 65.26 mcg*hr/mL/mg | Geometric Coefficient of Variation 18 |
90% CI: [4.7, 11.4]
90% CI: [20.67, 50.12]
90% CI: [22.57, 52.52]
90% CI: [34.26, 77.31]
Secondary
Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06293620 (MAD Cohorts) After Day 57 Administration
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The pharmacokinetic (PK) concentration population included all enrolled participants treated who had at least 1 measurable (greater than lower limit of quantification) concentration value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 0.7555 µg/mL | Geometric Coefficient of Variation 94 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 1.979 µg/mL | Geometric Coefficient of Variation 72 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 5.456 µg/mL | Geometric Coefficient of Variation 48 |
Secondary
Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK concentration population included all enrolled participants treated who had at least 1 measurable concentration value.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 1.526 mcg/mL | Geometric Coefficient of Variation 139 |
| Placebo SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 1.989 mcg/mL | Geometric Coefficient of Variation 183 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 1.706 mcg/mL | Geometric Coefficient of Variation 72 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 6.012 mcg/mL | Geometric Coefficient of Variation 65 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 5.184 mcg/mL | Geometric Coefficient of Variation 73 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 11.74 mcg/mL | Geometric Coefficient of Variation 56 |
Secondary
Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts)
Maximum serum concentration (Cmax) of PF-06293620 was observed directly from data.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The pharmacokinetic (PK) concentration population included all enrolled participants treated who had at least 1 measurable (greater than lower limit of quantification) concentration value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts) | 0.3907 mcg/mL | Geometric Coefficient of Variation 58 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts) | 2.896 mcg/mL | Geometric Coefficient of Variation 48 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts) | 7.222 mcg/mL | Geometric Coefficient of Variation 52 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts) | 22.30 mcg/mL | Geometric Coefficient of Variation 62 |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts) | 27.64 mcg/mL | Geometric Coefficient of Variation 20 |
Secondary
Observed Accumulation Ratio Based on AUC (Rac) of PF-06293620 (MAD Cohorts)
Observed accumulation ratio based on AUC (Rac) of PF-06293620 was calculated as AUCtau(Day57)/AUCtau(Day1).
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Observed Accumulation Ratio Based on AUC (Rac) of PF-06293620 (MAD Cohorts) | 1.833 ratio | Geometric Coefficient of Variation 64 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Observed Accumulation Ratio Based on AUC (Rac) of PF-06293620 (MAD Cohorts) | 3.446 ratio | Geometric Coefficient of Variation 36 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Observed Accumulation Ratio Based on AUC (Rac) of PF-06293620 (MAD Cohorts) | 2.148 ratio | Geometric Coefficient of Variation 30 |
Secondary
Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of PF-06293620 (MAD Cohorts)
Observed accumulation ratio based on Cmax (Rac,Cmax) of PF-06293620 was calculated as Cmax(Day57)/Cmax(Day1).
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of PF-06293620 (MAD Cohorts) | 1.302 ratio | Geometric Coefficient of Variation 114 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of PF-06293620 (MAD Cohorts) | 3.257 ratio | Geometric Coefficient of Variation 42 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of PF-06293620 (MAD Cohorts) | 2.188 ratio | Geometric Coefficient of Variation 22 |
Secondary
Steady-state Volume of Distribution (Vss) of PF-06293620 (SAD Cohorts)
Steady-state volume of distribution (Vss) of PF-06293620 was calculated as CL\*MRT, where MRT was the mean residence time calculated as (AUMCinf/AUCinf - infusion duration/2), AUMCinf was area under the moment curve from time 0 extrapolated to infinity; CL was the clearance. This outcome measure only applies to IV arms.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Steady-state Volume of Distribution (Vss) of PF-06293620 (SAD Cohorts) | 7.095 liters | Geometric Coefficient of Variation 21 |
Secondary
Terminal Elimination Half-life (Thalf) of PF-06293620 (MAD Cohorts) After Day 57 Administration
Terminal elimination half-life (Thalf) of PF-06293620 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Terminal Elimination Half-life (Thalf) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 10.37 days | Standard Deviation 2.22 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Terminal Elimination Half-life (Thalf) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 12.72 days | Standard Deviation 4.21 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Terminal Elimination Half-life (Thalf) of PF-06293620 (MAD Cohorts) After Day 57 Administration | 14.50 days | Standard Deviation 2.81 |
Secondary
Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts)
Terminal elimination half-life (Thalf) of PF-06293620 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts) | 7.33 days | — |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts) | 10.95 days | Standard Deviation 3.74 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts) | 14.66 days | Standard Deviation 4.21 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts) | 19.23 days | Standard Deviation 3.45 |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts) | 14.37 days | Standard Deviation 3.13 |
Secondary
Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration
Time for maximum serum concentration (Tmax) of PF-06293620 was observed directly from data as time of first occurrence.
Time frame: Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 240 hours |
| Placebo SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 168 hours |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 252 hours |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 144 hours |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 1 | 360 hours |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration | Day 57 | 120 hours |
Secondary
Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts)
Time for Maximum serum concentration (Tmax) of PF-06293620 was observed directly from data as time of first occurrence.
Time frame: Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85
Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts) | 168 hours | Full Range 58 |
| PF-06293620 0.3 mg/kg SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts) | 168 hours | Full Range 48 |
| PF-06293620 1.0 mg/kg SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts) | 252 hours | Full Range 52 |
| PF-06293620 3.0 mg/kg SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts) | 168 hours | Full Range 62 |
| PF-06293620 6.0 mg/kg SC (SAD Cohorts) | Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts) | 1.00 hours | Full Range 20 |