Rheumatoid Arthritis, Systemic Lupus Erythematosus
Conditions
Brief summary
This is a Phase 1 single and multiple dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06835375 in subjects with seropositive SLE or RA. The design is double-blind, sponsor open and placebo controlled. This study will include two parts: Part A and Part B. Part A will consist of single ascending dose cohorts, Part B of multiple ascending dose cohorts. This study will enroll up to a total of approximately 112 subjects at approximately 10 sites.
Interventions
DRUGPF-06835375
Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.
DRUGPlacebo
Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with Rheumatoid Arthritis: confirmed diagnosis according to 2010 ACR/EULAR criteria with symptom duration at least 6 months and positive with Rheumatoid Factor and/or anti citrullinated peptide antibody * Patients with Systemic Lupus Erythematosus: Confirmed diagnosis according to the SLICC Classification Criteria with symptom duration at least 6 months and at least one of the following: positive antinuclear antibody titer, positive anti-dsDNA, anti-Smith antibodies
Exclusion criteria
* Active central nervous system manifestations, systemic vasculitis or pleuro/pericarditis * Active lupus nephritis * Treatment with B cell depleting agents within 52 weeks prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicity (DLT) | From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | DLT was defined as any of the following events meeting the criteria: (1) \>=2 participants within a dose cohort developed Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade 3 adverse event considered to be serious in the same organ system or 1 participant developed a CTCAE v4.0 Grade 4 or higher SAE considered related to study drug; (2) 50% or more participants within a dose cohort experienced a CTCAE v4.0 Grade 3 or higher infusion reaction; (3) a confirmed or probable case of Progressive Multifocal Leukoencephalopathy was observed; (4) the mean exposure for the treatment group reached or exceeded the exposure stopping limit of Cav of 261 mg/mL, or, based on the observed data, the group mean Cav of the next planned dose was projected to exceed the exposure stopping limit. Cav = average serum concentration. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function. |
| Number of Participants With All-Causality and Treatment-Related TEAEs | From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. A 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; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Permanent Discontinuation Due to TEAEs | From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | Hematology included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein and creatine kinase. Urinalysis included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy and creatinine. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. Baseline was the last pre-dose measurement (first treatment for MAD cohorts). |
| Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | Criteria for abnormality in vital signs: supine pulse rate \<40 beats per minute (bpm) or \>120 bpm; standing pulse rate \<40 bpm or \>120 bpm; sitting systolic blood pressure (BP) \<90 mmHg, maximum increase or decrease from baseline of \>=30 mmHg; sitting diastolic BP \<50 mmHg, maximum increase or decrease from baseline of \>=20 mmHg. Baseline was defined as the last pre-dose measurement in Day 1. Only those categories in which at least 1 participant had data were reported. |
| Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | ECG abnormalities criteria included: 1) maximum QTc interval (ms): 450\<= QTc \<480, 480\<= QTc \<500, and QTc \>=500; QTc maximum increase from baseline (ms): 30\<= change \<60, and change \>=60; 2) maximum PR interval (ms): \>=300; PR increase from baseline (ms): baseline \>200 with 25% increase at maximum, baseline \<=200 with 50% increase at maximum; 3) maximum QRS (ms): \>=140; QRS increase from baseline (ms) \>=50%. QTcF indicates QT interval corrected using the Fridericia's formula. QTcB indicates QT interval corrected using the Bazett's formula. Baseline was defined as the average of the triplicate pre-dose recordings at Day 1. Only those categories in which at least 1 participant had data were reported. |
| Number of Participants With All-Causality and Treatment-Related Infections and Infestations | From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. The incidence of AEs by system organ class infections and infestations was reported here. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates | AUCtau is area under the serum concentration-time profile from time 0 to time tau, the dosing interval, where tau= 28 days. AUCtau for PF-06835375 was determined using linear/log trapezoidal method. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated. |
| AUClast of PF-06835375 Following Multiple Doses in Part B (MAD) | Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates | AUClast is the area under the curve from time zero to last quantifiable concentration. AUClast for PF-06835375 was determined using linear/log trapezoidal method. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated. |
| Minimum Observed Serum Trough Concentration (Cmin) of PF-06835375 Following Multiple Doses in Part B (MAD) | Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates | Cmin is minimum observed serum trough concentration. Cmin was observed directly from data. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated. |
| B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | Screening, Day 1, 2, 4, 8, 15, 29, 36 (Part B only), 43, 57, 85, 113, and every 4 weeks until criteria for end of study met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | Blood samples for the assessment of B cell were collected and analyzed by flow cytometry. Baseline was defined as the average of screening and pre-dose measures. |
| Peak-to-trough Fluctuation (PTF) of PF-06835375 Following Multiple Doses in Part B (MAD) | Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates | PTF is peak-to-trough fluctuation at steady state. PTF = (Cmax-Cmin)/Cav. Cav is average serum concentration. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated. |
| Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Day 1, 15, 29, 43, 57, 85, 113, and every 4 weeks until criteria for end of study met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | To evaluate the immunogenicity as measured by presence of ADA and NAb in participants treated with PF-06835375. |
| Observed Accumulation Ratio (Rac) of PF-06835375 Following Multiple Doses in Part B (MAD) | Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates | Rac is observed accumulation ratio. Rac = Day 29 AUCtau / Day 1 AUCtau. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated. |
| cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | Screening, Day 1, 2, 4, 8, 15, 29, 36 (Part B only), 43, 57, 85, 113, and every 4 weeks until criteria for end of study met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B) | Blood samples for the assessment of circulating follicular T helper like (cTfh) cell were collected and analyzed by flow cytometry. Baseline was defined as the average of screening and pre-dose measures. |
| Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD) | Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates | Cmax is maximum observed serum concentration. Cmax for PF-06835375 was observed directly from data. |
| Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD) | Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates | Tmax is the time for Cmax. Tmax for PF-06835375 was observed directly from data as time of first occurrence. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD) | Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates | AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD) | Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates | AUClast is the area under the curve from time zero to last quantifiable concentration. AUClast for PF-06835375 was determined using linear/log trapezoidal method. |
| Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates | Cmax is maximum observed serum concentration. Cmax for PF-06835375 was observed directly from data. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated. |
| Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates | Tmax is the time for Cmax. Tmax for PF-06835375 was observed directly from data as time of first occurrence. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated. |
Countries
United States
Participant flow
Pre-assignment details
This study included two parts: Part A, consisting of 7 single ascending dose (SAD) cohorts (placebo and PF-06835375 0.03 mg, 0.1 mg, 0.3 mg, 1 mg, 3 mg, 6 mg); and Part B, consisting 6 multiple ascending dose (MAD) cohorts (placebo and PF-06835375 0.3 mg, 1 mg, 3 mg, 6 mg, 10 mg). In Part A (SAD), 32 participants were assigned to treatment, 1 of whom was not treated. In Part B (MAD), 42 participants were screened and treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV SAD Participants received single dose of placebo on Day 1 as an intravenous (IV) infusion. | 8 |
| PF-06835375 0.03 mg IV SAD Participants received single dose of PF-06835375 0.03 mg on Day 1 as an IV infusion. | 3 |
| PF-06835375 0.1 mg IV SAD Participants received single dose of PF-06835375 0.1 mg on Day 1 as an IV infusion. | 3 |
| PF-06835375 0.3 mg IV SAD Participants received single dose of PF-06835375 0.3 mg on Day 1 as an IV infusion. | 3 |
| PF-06835375 1 mg IV SAD Participants received single dose of PF-06835375 1 mg on Day 1 as an IV infusion. | 3 |
| PF-06835375 3 mg IV SAD Participants received single dose of PF-06835375 3 mg on Day 1 as an IV infusion. | 6 |
| PF-06835375 6 mg IV SAD Participants received single dose of PF-06835375 6 mg on Day 1 as an IV infusion. | 5 |
| Placebo SC MAD Participants received two doses of placebo subcutaneously (SC) with first dose on Day 1 and the repeated dose on Day 29. | 11 |
| PF-06835375 0.3 mg SC MAD Participants received two doses of PF-06835375 0.3 mg SC with first dose on Day 1 and the repeated dose on Day 29. | 6 |
| PF-06835375 1 mg SC MAD Participants received two doses of PF-06835375 1 mg SC with first dose on Day 1 and the repeated dose on Day 29. | 6 |
| PF-06835375 3 mg SC MAD Participants received two doses of PF-06835375 3 mg SC with first dose on Day 1 and the repeated dose on Day 29. | 7 |
| PF-06835375 6 mg SC MAD Participants received two doses of PF-06835375 6 mg SC with first dose on Day 1 and the repeated dose on Day 29. | 6 |
| PF-06835375 10 mg SC MAD Participants received two doses of PF-06835375 10 mg SC with first dose on Day 1 and the repeated dose on Day 29. | 6 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo IV SAD | PF-06835375 0.03 mg IV SAD | PF-06835375 0.1 mg IV SAD | PF-06835375 0.3 mg IV SAD | PF-06835375 1 mg IV SAD | PF-06835375 3 mg IV SAD | PF-06835375 6 mg IV SAD | Placebo SC MAD | PF-06835375 0.3 mg SC MAD | PF-06835375 1 mg SC MAD | PF-06835375 3 mg SC MAD | PF-06835375 6 mg SC MAD | PF-06835375 10 mg SC MAD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.00 Years STANDARD_DEVIATION 11.58 | 53.33 Years STANDARD_DEVIATION 11.02 | 47.33 Years STANDARD_DEVIATION 15.53 | 57.33 Years STANDARD_DEVIATION 6.03 | 54.00 Years STANDARD_DEVIATION 10.15 | 52.33 Years STANDARD_DEVIATION 13.95 | 54.00 Years STANDARD_DEVIATION 5.66 | 48.64 Years STANDARD_DEVIATION 13.6 | 52.00 Years STANDARD_DEVIATION 10.56 | 54.17 Years STANDARD_DEVIATION 7.7 | 53.57 Years STANDARD_DEVIATION 8.2 | 61.67 Years STANDARD_DEVIATION 10.8 | 58.50 Years STANDARD_DEVIATION 9.25 | 53.26 Years STANDARD_DEVIATION 10.71 |
| Age, Customized <18 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 18-44 | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 15 Participants |
| Age, Customized 45-64 | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 5 Participants | 6 Participants | 4 Participants | 6 Participants | 5 Participants | 2 Participants | 3 Participants | 48 Participants |
| Age, Customized >=65 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 9 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 6 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 4 Participants | 9 Participants | 6 Participants | 4 Participants | 6 Participants | 5 Participants | 5 Participants | 54 Participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 6 Participants | 5 Participants | 11 Participants | 5 Participants | 4 Participants | 7 Participants | 5 Participants | 4 Participants | 65 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 5 | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 8 / 8 | 3 / 3 | 3 / 3 | 2 / 3 | 3 / 3 | 6 / 6 | 5 / 5 | 9 / 11 | 4 / 6 | 4 / 6 | 5 / 7 | 4 / 6 | 6 / 6 |
| serious Total, serious adverse events | 1 / 8 | 1 / 3 | 0 / 3 | 1 / 3 | 0 / 3 | 0 / 6 | 0 / 5 | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With All-Causality and Treatment-Related Infections and Infestations
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. The incidence of AEs by system organ class infections and infestations was reported here.
Time frame: From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 1 Participants |
| Placebo IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 4 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 2 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 3 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 2 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 3 Participants |
| Placebo SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| Placebo SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 3 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 2 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 3 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 2 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with treatment-related Infections and Infestations | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With All-Causality and Treatment-Related Infections and Infestations | Number of Participants with all-causality Infections and Infestations | 2 Participants |
Primary
Number of Participants With All-Causality and Treatment-Related TEAEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. A 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; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| Placebo IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 8 Participants |
| Placebo IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 3 Participants |
| Placebo IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 1 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 3 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 1 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 3 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 2 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 3 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 2 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 6 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 6 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 5 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 3 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| Placebo SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| Placebo SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 3 Participants |
| Placebo SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| Placebo SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 9 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 4 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 3 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 4 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 5 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 5 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 2 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 4 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality TEAEs | 6 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of Participants with treatment-related TEAEs | 2 Participants |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis
Hematology included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein and creatine kinase. Urinalysis included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy and creatinine. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. Baseline was the last pre-dose measurement (first treatment for MAD cohorts).
Time frame: From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| Placebo IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 1 Participants |
| Placebo IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 1 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| Placebo SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| Placebo SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| Placebo SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 1 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver function tests (AST and ALT increased) | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated liver enzymes (AST and ALT increased) | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Elevated creatine phosphokinase (CPK) | 0 Participants |
Primary
Number of Participants With Dose-Limiting Toxicity (DLT)
DLT was defined as any of the following events meeting the criteria: (1) \>=2 participants within a dose cohort developed Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade 3 adverse event considered to be serious in the same organ system or 1 participant developed a CTCAE v4.0 Grade 4 or higher SAE considered related to study drug; (2) 50% or more participants within a dose cohort experienced a CTCAE v4.0 Grade 3 or higher infusion reaction; (3) a confirmed or probable case of Progressive Multifocal Leukoencephalopathy was observed; (4) the mean exposure for the treatment group reached or exceeded the exposure stopping limit of Cav of 261 mg/mL, or, based on the observed data, the group mean Cav of the next planned dose was projected to exceed the exposure stopping limit. Cav = average serum concentration.
Time frame: From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo IV SAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Placebo SC MAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
Primary
Number of Participants With Permanent Discontinuation Due to TEAEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo IV SAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| Placebo SC MAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 1 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Permanent Discontinuation Due to TEAEs | 0 Participants |
Primary
Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria
ECG abnormalities criteria included: 1) maximum QTc interval (ms): 450\<= QTc \<480, 480\<= QTc \<500, and QTc \>=500; QTc maximum increase from baseline (ms): 30\<= change \<60, and change \>=60; 2) maximum PR interval (ms): \>=300; PR increase from baseline (ms): baseline \>200 with 25% increase at maximum, baseline \<=200 with 50% increase at maximum; 3) maximum QRS (ms): \>=140; QRS increase from baseline (ms) \>=50%. QTcF indicates QT interval corrected using the Fridericia's formula. QTcB indicates QT interval corrected using the Bazett's formula. Baseline was defined as the average of the triplicate pre-dose recordings at Day 1. Only those categories in which at least 1 participant had data were reported.
Time frame: From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 1 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 2 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 4 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 0 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 2 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 4 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 1 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 2 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 1 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 1 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 2 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 1 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 2 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 1 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 1 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 2 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 3 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 4 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 4 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 6 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 3 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 2 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 2 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 1 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 1 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 1 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 3 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 1 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 3 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 2 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 1 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 2 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 1 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 1 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcF Interval (ms) <480 | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcB Maximum Increase From Baseline (ms) <60 | 3 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QTcB Interval (ms) >=500 | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcB Interval (ms) <500 | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 450<= Maximum QTcB Interval (ms) <480 | 3 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | Maximum QRS (ms) >=140 | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 480<= Maximum QTcF Interval (ms) <500 | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria | 30<= QTcF Maximum Increase From Baseline (ms) <60 | 0 Participants |
Primary
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria
Criteria for abnormality in vital signs: supine pulse rate \<40 beats per minute (bpm) or \>120 bpm; standing pulse rate \<40 bpm or \>120 bpm; sitting systolic blood pressure (BP) \<90 mmHg, maximum increase or decrease from baseline of \>=30 mmHg; sitting diastolic BP \<50 mmHg, maximum increase or decrease from baseline of \>=20 mmHg. Baseline was defined as the last pre-dose measurement in Day 1. Only those categories in which at least 1 participant had data were reported.
Time frame: From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 3 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 1 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 4 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| Placebo IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 2 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 1 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 1 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 2 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 3 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 2 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 1 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 1 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 3 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 1 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 1 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 4 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 0 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 1 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 0 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 3 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 4 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 0 Participants |
| Placebo SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 1 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 2 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 2 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 2 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 3 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 2 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 1 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 1 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 1 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 2 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Diastolic BP <50 mmHg | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Sitting Systolic BP <90 mmHg | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Diastolic BP >= 20 mmHg | 2 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Increase from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Maximum Decrease from Baseline in Sitting Systolic BP >= 30 mmHg | 1 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.
Time frame: From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 2 Participants |
| Placebo IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 1 Participants |
| Placebo IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 1 Participants |
| Placebo IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 3 Participants |
| Placebo IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 4 Participants |
| Placebo IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 1 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 2 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 1 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 2 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 1 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 0 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 2 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 3 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 2 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 2 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 4 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 3 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 3 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 0 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 1 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 4 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 1 Participants |
| Placebo SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 0 Participants |
| Placebo SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 4 Participants |
| Placebo SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 5 Participants |
| Placebo SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| Placebo SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 3 Participants |
| Placebo SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 2 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 0 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 3 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 2 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 0 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 3 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 4 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 3 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 2 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 1 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 1 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 3 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 1 Participants |
| PF-06835375 6 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 1 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (treatment-related) | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (all causalities) | 3 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (treatment-related) | 1 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate (all causalities) | 3 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe (all causalities) | 0 Participants |
| PF-06835375 10 mg SC MAD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild (treatment-related) | 1 Participants |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD)
AUCtau is area under the serum concentration-time profile from time 0 to time tau, the dosing interval, where tau= 28 days. AUCtau for PF-06835375 was determined using linear/log trapezoidal method. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated.
Time frame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo IV SAD | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 9309 ng*hr/mL | Geometric Coefficient of Variation 62 |
| Placebo IV SAD | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 1964 ng*hr/mL | Geometric Coefficient of Variation 130 |
| PF-06835375 0.03 mg IV SAD | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 11010 ng*hr/mL | Geometric Coefficient of Variation 84 |
| PF-06835375 0.03 mg IV SAD | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 25610 ng*hr/mL | Geometric Coefficient of Variation 125 |
| PF-06835375 0.1 mg IV SAD | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 76450 ng*hr/mL | Geometric Coefficient of Variation 142 |
| PF-06835375 0.1 mg IV SAD | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 28070 ng*hr/mL | Geometric Coefficient of Variation 251 |
| PF-06835375 0.3 mg IV SAD | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 88540 ng*hr/mL | Geometric Coefficient of Variation 154 |
| PF-06835375 0.3 mg IV SAD | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 70630 ng*hr/mL | Geometric Coefficient of Variation 202 |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD)
AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time.
Time frame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD) | NA nanogram*hour/milliliter (ng*hr/mL) | — |
| PF-06835375 0.1 mg IV SAD | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD) | 1573 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 2409 |
| PF-06835375 0.3 mg IV SAD | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD) | 7467 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 84 |
| PF-06835375 1 mg IV SAD | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD) | 88190 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| PF-06835375 3 mg IV SAD | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD) | 288000 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD)
AUClast is the area under the curve from time zero to last quantifiable concentration. AUClast for PF-06835375 was determined using linear/log trapezoidal method.
Time frame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD) | NA ng*hr/mL | — |
| PF-06835375 0.03 mg IV SAD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD) | NA ng*hr/mL | — |
| PF-06835375 0.1 mg IV SAD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD) | 1380 ng*hr/mL | Geometric Coefficient of Variation 2950 |
| PF-06835375 0.3 mg IV SAD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD) | 7327 ng*hr/mL | Geometric Coefficient of Variation 85 |
| PF-06835375 1 mg IV SAD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD) | 87120 ng*hr/mL | Geometric Coefficient of Variation 36 |
| PF-06835375 3 mg IV SAD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD) | 287400 ng*hr/mL | Geometric Coefficient of Variation 30 |
Secondary
AUClast of PF-06835375 Following Multiple Doses in Part B (MAD)
AUClast is the area under the curve from time zero to last quantifiable concentration. AUClast for PF-06835375 was determined using linear/log trapezoidal method. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated.
Time frame: Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | AUClast of PF-06835375 Following Multiple Doses in Part B (MAD) | 9346 ng*hr/mL | Geometric Coefficient of Variation 61 |
| PF-06835375 0.03 mg IV SAD | AUClast of PF-06835375 Following Multiple Doses in Part B (MAD) | 22050 ng*hr/mL | Geometric Coefficient of Variation 146 |
| PF-06835375 0.1 mg IV SAD | AUClast of PF-06835375 Following Multiple Doses in Part B (MAD) | 84370 ng*hr/mL | Geometric Coefficient of Variation 160 |
| PF-06835375 0.3 mg IV SAD | AUClast of PF-06835375 Following Multiple Doses in Part B (MAD) | 96610 ng*hr/mL | Geometric Coefficient of Variation 141 |
Secondary
B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375
Blood samples for the assessment of B cell were collected and analyzed by flow cytometry. Baseline was defined as the average of screening and pre-dose measures.
Time frame: Screening, Day 1, 2, 4, 8, 15, 29, 36 (Part B only), 43, 57, 85, 113, and every 4 weeks until criteria for end of study met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All enrolled participants who received at least 1 dose of study treatment and had at least 1 pharmacodynamic measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 37.693 Percentage of decrease from baseline | Geometric Coefficient of Variation 43.0477 |
| PF-06835375 0.03 mg IV SAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 67.283 Percentage of decrease from baseline | Geometric Coefficient of Variation 29.3555 |
| PF-06835375 0.1 mg IV SAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 84.978 Percentage of decrease from baseline | Geometric Coefficient of Variation 5.9053 |
| PF-06835375 0.3 mg IV SAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 94.052 Percentage of decrease from baseline | Geometric Coefficient of Variation 2.4246 |
| PF-06835375 1 mg IV SAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 98.546 Percentage of decrease from baseline | Geometric Coefficient of Variation 0.1627 |
| PF-06835375 3 mg IV SAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 98.588 Percentage of decrease from baseline | Geometric Coefficient of Variation 1.0295 |
| PF-06835375 6 mg IV SAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 99.326 Percentage of decrease from baseline | Geometric Coefficient of Variation 0.3272 |
| Placebo SC MAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 41.854 Percentage of decrease from baseline | Geometric Coefficient of Variation 52.5341 |
| PF-06835375 0.3 mg SC MAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 91.056 Percentage of decrease from baseline | Geometric Coefficient of Variation 12.6425 |
| PF-06835375 1 mg SC MAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 99.650 Percentage of decrease from baseline | Geometric Coefficient of Variation 0.4036 |
| PF-06835375 3 mg SC MAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 99.287 Percentage of decrease from baseline | Geometric Coefficient of Variation 0.63 |
| PF-06835375 6 mg SC MAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 99.278 Percentage of decrease from baseline | Geometric Coefficient of Variation 1.4476 |
| PF-06835375 10 mg SC MAD | B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 99.134 Percentage of decrease from baseline | Geometric Coefficient of Variation 0.9983 |
Secondary
Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD)
Cmax is maximum observed serum concentration. Cmax for PF-06835375 was observed directly from data. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated.
Time frame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo IV SAD | Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 5.743 ng/mL | Geometric Coefficient of Variation 148 |
| Placebo IV SAD | Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 26.92 ng/mL | Geometric Coefficient of Variation 68 |
| PF-06835375 0.03 mg IV SAD | Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 89.68 ng/mL | Geometric Coefficient of Variation 93 |
| PF-06835375 0.03 mg IV SAD | Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 34.82 ng/mL | Geometric Coefficient of Variation 79 |
| PF-06835375 0.1 mg IV SAD | Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 77.72 ng/mL | Geometric Coefficient of Variation 150 |
| PF-06835375 0.1 mg IV SAD | Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 209.6 ng/mL | Geometric Coefficient of Variation 115 |
| PF-06835375 0.3 mg IV SAD | Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 257.8 ng/mL | Geometric Coefficient of Variation 204 |
| PF-06835375 0.3 mg IV SAD | Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 262.1 ng/mL | Geometric Coefficient of Variation 224 |
Secondary
cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375
Blood samples for the assessment of circulating follicular T helper like (cTfh) cell were collected and analyzed by flow cytometry. Baseline was defined as the average of screening and pre-dose measures.
Time frame: Screening, Day 1, 2, 4, 8, 15, 29, 36 (Part B only), 43, 57, 85, 113, and every 4 weeks until criteria for end of study met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All enrolled participants who received at least 1 dose of study treatment and had at least 1 pharmacodynamic measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 45.227 Percentage of decrease from baseline | Geometric Coefficient of Variation 48.6385 |
| PF-06835375 0.03 mg IV SAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 62.360 Percentage of decrease from baseline | Geometric Coefficient of Variation 23.1206 |
| PF-06835375 0.1 mg IV SAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 84.994 Percentage of decrease from baseline | Geometric Coefficient of Variation 11.2007 |
| PF-06835375 0.3 mg IV SAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 89.324 Percentage of decrease from baseline | Geometric Coefficient of Variation 6.3399 |
| PF-06835375 1 mg IV SAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 98.675 Percentage of decrease from baseline | Geometric Coefficient of Variation 1.2762 |
| PF-06835375 3 mg IV SAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 97.283 Percentage of decrease from baseline | Geometric Coefficient of Variation 3.0481 |
| PF-06835375 6 mg IV SAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 97.789 Percentage of decrease from baseline | Geometric Coefficient of Variation 3.1257 |
| Placebo SC MAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 58.116 Percentage of decrease from baseline | Geometric Coefficient of Variation 52.5069 |
| PF-06835375 0.3 mg SC MAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 89.540 Percentage of decrease from baseline | Geometric Coefficient of Variation 14.8599 |
| PF-06835375 1 mg SC MAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 95.442 Percentage of decrease from baseline | Geometric Coefficient of Variation 5.3905 |
| PF-06835375 3 mg SC MAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 96.683 Percentage of decrease from baseline | Geometric Coefficient of Variation 1.8503 |
| PF-06835375 6 mg SC MAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 97.721 Percentage of decrease from baseline | Geometric Coefficient of Variation 1.6523 |
| PF-06835375 10 mg SC MAD | cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 | 98.118 Percentage of decrease from baseline | Geometric Coefficient of Variation 0.8825 |
Secondary
Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD)
Cmax is maximum observed serum concentration. Cmax for PF-06835375 was observed directly from data.
Time frame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD) | NA nanogram/milliliter (ng/mL) | — |
| PF-06835375 0.03 mg IV SAD | Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD) | NA nanogram/milliliter (ng/mL) | — |
| PF-06835375 0.1 mg IV SAD | Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD) | 103.0 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 197 |
| PF-06835375 0.3 mg IV SAD | Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD) | 208.7 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| PF-06835375 1 mg IV SAD | Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD) | 994.7 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 29 |
| PF-06835375 3 mg IV SAD | Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD) | 2645 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
Secondary
Minimum Observed Serum Trough Concentration (Cmin) of PF-06835375 Following Multiple Doses in Part B (MAD)
Cmin is minimum observed serum trough concentration. Cmin was observed directly from data. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated.
Time frame: Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | Minimum Observed Serum Trough Concentration (Cmin) of PF-06835375 Following Multiple Doses in Part B (MAD) | NA ng/mL | — |
| PF-06835375 0.03 mg IV SAD | Minimum Observed Serum Trough Concentration (Cmin) of PF-06835375 Following Multiple Doses in Part B (MAD) | 6.075 ng/mL | Geometric Coefficient of Variation 80 |
| PF-06835375 0.1 mg IV SAD | Minimum Observed Serum Trough Concentration (Cmin) of PF-06835375 Following Multiple Doses in Part B (MAD) | 11.81 ng/mL | Geometric Coefficient of Variation 434 |
| PF-06835375 0.3 mg IV SAD | Minimum Observed Serum Trough Concentration (Cmin) of PF-06835375 Following Multiple Doses in Part B (MAD) | 9.410 ng/mL | Geometric Coefficient of Variation 199 |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375
To evaluate the immunogenicity as measured by presence of ADA and NAb in participants treated with PF-06835375.
Time frame: Day 1, 15, 29, 43, 57, 85, 113, and every 4 weeks until criteria for end of study met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Population: All enrolled participants who received at least 1 dose of study treatment and had at least 1 pharmacodynamic measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 0 Participants |
| Placebo IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 0 Participants |
| PF-06835375 0.03 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 0 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 1 Participants |
| PF-06835375 0.1 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 1 Participants |
| PF-06835375 0.3 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 1 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 3 Participants |
| PF-06835375 1 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 3 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 2 Participants |
| PF-06835375 3 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 2 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 2 Participants |
| PF-06835375 6 mg IV SAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 3 Participants |
| Placebo SC MAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 1 Participants |
| Placebo SC MAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 3 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 1 Participants |
| PF-06835375 0.3 mg SC MAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 1 Participants |
| PF-06835375 1 mg SC MAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 1 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive NAb | 2 Participants |
| PF-06835375 3 mg SC MAD | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 | Number of ADA or NAb evaluable participants with positive ADA | 2 Participants |
Secondary
Observed Accumulation Ratio (Rac) of PF-06835375 Following Multiple Doses in Part B (MAD)
Rac is observed accumulation ratio. Rac = Day 29 AUCtau / Day 1 AUCtau. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated.
Time frame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | Observed Accumulation Ratio (Rac) of PF-06835375 Following Multiple Doses in Part B (MAD) | NA ratio | — |
| PF-06835375 0.03 mg IV SAD | Observed Accumulation Ratio (Rac) of PF-06835375 Following Multiple Doses in Part B (MAD) | 2.410 ratio | Geometric Coefficient of Variation 74 |
| PF-06835375 0.1 mg IV SAD | Observed Accumulation Ratio (Rac) of PF-06835375 Following Multiple Doses in Part B (MAD) | 2.977 ratio | Geometric Coefficient of Variation 79 |
| PF-06835375 0.3 mg IV SAD | Observed Accumulation Ratio (Rac) of PF-06835375 Following Multiple Doses in Part B (MAD) | 2.001 ratio | Geometric Coefficient of Variation 209 |
Secondary
Peak-to-trough Fluctuation (PTF) of PF-06835375 Following Multiple Doses in Part B (MAD)
PTF is peak-to-trough fluctuation at steady state. PTF = (Cmax-Cmin)/Cav. Cav is average serum concentration. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated.
Time frame: Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV SAD | Peak-to-trough Fluctuation (PTF) of PF-06835375 Following Multiple Doses in Part B (MAD) | NA ratio | — |
| PF-06835375 0.03 mg IV SAD | Peak-to-trough Fluctuation (PTF) of PF-06835375 Following Multiple Doses in Part B (MAD) | 2.037 ratio | Geometric Coefficient of Variation 26 |
| PF-06835375 0.1 mg IV SAD | Peak-to-trough Fluctuation (PTF) of PF-06835375 Following Multiple Doses in Part B (MAD) | 1.687 ratio | Geometric Coefficient of Variation 31 |
| PF-06835375 0.3 mg IV SAD | Peak-to-trough Fluctuation (PTF) of PF-06835375 Following Multiple Doses in Part B (MAD) | 1.830 ratio | Geometric Coefficient of Variation 35 |
Secondary
Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD)
Tmax is the time for Cmax. Tmax for PF-06835375 was observed directly from data as time of first occurrence.
Time frame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo IV SAD | Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD) | NA hour (hr) |
| PF-06835375 0.03 mg IV SAD | Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD) | NA hour (hr) |
| PF-06835375 0.1 mg IV SAD | Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD) | 2.17 hour (hr) |
| PF-06835375 0.3 mg IV SAD | Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD) | 2.08 hour (hr) |
| PF-06835375 1 mg IV SAD | Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD) | 2.24 hour (hr) |
| PF-06835375 3 mg IV SAD | Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD) | 3.96 hour (hr) |
Secondary
Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD)
Tmax is the time for Cmax. Tmax for PF-06835375 was observed directly from data as time of first occurrence. There were less than 3 quantifiable concentrations for participants in PF-06835375 0.3 mg SC MAD cohort, therefore the serum PK parameters were not calculated.
Time frame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo IV SAD | Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 170 hr |
| Placebo IV SAD | Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 169 hr |
| PF-06835375 0.03 mg IV SAD | Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 169 hr |
| PF-06835375 0.03 mg IV SAD | Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 168 hr |
| PF-06835375 0.1 mg IV SAD | Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 169 hr |
| PF-06835375 0.1 mg IV SAD | Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 171 hr |
| PF-06835375 0.3 mg IV SAD | Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 1 | 144 hr |
| PF-06835375 0.3 mg IV SAD | Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) | Day 29 | 121 hr |