Non-alcoholic Steatohepatitis
Conditions
Keywords
Non-alcoholic steatohepatitis; Type 2 Diabetes Mellitus
Brief summary
This is a double-blind, placebo-controlled study in adults with non-alcoholic steatohepatitis and Type 2 Diabetes Mellitis on stable dose of metformin monotherapy. Participants will be treated for 16 weeks with placebo or 1 of 2 doses of investigational product to determine the effect on liver fat, HbA1c, safety, tolerability and pharmacodynamics.
Interventions
DRUGPlacebo
Placebo
DRUGPF-06835919
150 mg once daily
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Males, or females of nonchildbearing potential * 18 to 70 years of age * Type 2 Diabetes Mellitus * Liver fat \>/=8% by MRI-PDFF * On stable dose of metformin monotherapy for at least 2 months (at a dose of at least 500 mg daily)
Exclusion criteria
* History of other liver disease * Unable to have an MRI performed * Significant weight loss in the previous month and/or participant in current weight loss program * History of diabetic complications with end-organ damage
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Whole Liver Fat at Week 16 | Baseline, Week 16. | Whole liver fat was measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF). |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 | Baseline, Week 16. | A sufficient amount of blood was collected for the analysis of plasma HbA1c. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of Participants With Clinical Laboratory Abnormalities | Up to 21 weeks. | Clinical laboratory tests included hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy). The abnormality criteria were standard sponsor reporting criteria. |
| Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | Up to 21 weeks. | Vital signs data meeting the following criteria were reported: sitting diastolic blood pressure (DBP) \<50 mmHg or \>= 20 mmHg increase or \>= 20 mmHg decrease, sitting systolic blood pressure (SBP) blood pressure \<90 mmHg or \>=30 mmHg increase or \>=30 mmHg decrease. |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | Up to 21 weeks. | ECG data meeting the following criteria were reported: PR interval value \>=300 msec, QRS interval percent change \>= 50%, QTcF interval value \>450 msec and \<=480 msec, or change \>30 msec and \<=60 msec, or change \>60 msec. |
| Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. | Blood samples were collected to ensure sufficient serum for the analysis of hs-CRP. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to 21 weeks. | An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or that was considered to be an important medical event. An AE was considered TEAE if the event occurred during the on-treatment period. The causality of AEs were assessed by the investigator using clinical judgement. A severe AE was an event that prevents normal everyday activities. |
| Change From Baseline in Fasting Glucose Over 16 Weeks | From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. | A sufficient amount of blood was collected for the analysis of plasma glucose. |
| Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. | HOMA-IR values were derived from fasting plasma insulin and glucose values. Greater reduction from baseline in HOMA-IR scale values shows greater effects on glycemic metabolism. |
| Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. | ALT was assessed as one of the clinical laboratory chemistry tests. |
| Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | From Baseline to Week 2, Week, 4, Week 8, and Week 12. | A sufficient amount of blood was collected for the analysis of plasma HbA1c. |
| Change From Baseline in Fasting Insulin Over 16 Weeks | From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. | A sufficient amount of blood was collected for the analysis of plasma insulin. The unit of insulin is milli-international units per liter (mIU/L). |
| Number of Participants With Hypoglycemia TEAEs | Up to 21 weeks. | Hypoglycemic AEs were routinely monitored during participation in the study. Hypoglycemic AE was defined as 1 of the following: 1. Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemic AE but a plasma glucose value of \<70 milligram per deciliter (mg/dL) using glucometer; 2. Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemic AEs were accompanied with a glucose value of \<70 mg/dL using glucometer and the clinical picture included prompt resolution with food intake, subcutaneous glucagon or intravenous (IV) glucose; 3. Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemic AEs were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration of \<70 mg/dL, and the clinical picture included prompt resolution with food intake, subcutaneous glucagon, or IV glucose. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo All participants received placebo matched to PF-06835919 once daily (QD) for 16 Weeks. | 54 |
| PF-06835919 150 mg All participants received PF-06835919 150 mg QD for 16 Weeks. | 55 |
| PF-06835919 300 mg All participants received PF-06835919 300 mg QD for 16 Weeks. | 55 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Other reasons not specified | 1 | 1 | 3 |
| Overall Study | Protocol Violation | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | PF-06835919 150 mg | PF-06835919 300 mg |
|---|---|---|---|---|
| Age, Customized 18-64 Years | 117 Participants | 39 Participants | 38 Participants | 40 Participants |
| Age, Customized <18 Years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 65-84 Years | 47 Participants | 15 Participants | 17 Participants | 15 Participants |
| Age, Customized >=85 Years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants | 9 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 22 Participants | 6 Participants | 8 Participants | 8 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 126 Participants | 38 Participants | 43 Participants | 45 Participants |
| Sex: Female, Male Female | 93 Participants | 35 Participants | 26 Participants | 32 Participants |
| Sex: Female, Male Male | 71 Participants | 19 Participants | 29 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 55 | 0 / 55 |
| other Total, other adverse events | 7 / 54 | 10 / 55 | 1 / 55 |
| serious Total, serious adverse events | 0 / 54 | 1 / 55 | 0 / 55 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16
A sufficient amount of blood was collected for the analysis of plasma HbA1c.
Time frame: Baseline, Week 16.
Population: The FAS included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants who were in the FAS and had the HbA1c value at Week 16 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 | -0.14 Percent of HbA1c | Standard Deviation 0.947 |
| PF-06835919 150 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 | -0.24 Percent of HbA1c | Standard Deviation 0.779 |
| PF-06835919 300 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 | -0.32 Percent of HbA1c | Standard Deviation 0.764 |
p-value: 0.633690% CI: [-0.36, 0.2]Mixed Models Analysis
p-value: 0.126690% CI: [-0.52, 0.02]Mixed Models Analysis
Primary
Percent Change From Baseline in Whole Liver Fat at Week 16
Whole liver fat was measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF).
Time frame: Baseline, Week 16.
Population: The full analysis set (FAS) included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants who were in the FAS and had the liver fat value at Week 16 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Whole Liver Fat at Week 16 | -3.21 Percent change | Standard Deviation 26.997 |
| PF-06835919 150 mg | Percent Change From Baseline in Whole Liver Fat at Week 16 | -16.12 Percent change | Standard Deviation 22.773 |
| PF-06835919 300 mg | Percent Change From Baseline in Whole Liver Fat at Week 16 | -4.36 Percent change | Standard Deviation 45.825 |
p-value: 0.069690% CI: [-22.37, -1.25]ANCOVA
p-value: 0.028890% CI: [-24.18, -3.89]ANCOVA
Secondary
Change From Baseline in Fasting Glucose Over 16 Weeks
A sufficient amount of blood was collected for the analysis of plasma glucose.
Time frame: From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Population: The FAS included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants who were in the FAS and had the glucose values at each timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 12 | 8.94 milligram per deciliter (mg/dL) | Standard Deviation 40.207 |
| Placebo | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 8 | 6.55 milligram per deciliter (mg/dL) | Standard Deviation 36.609 |
| Placebo | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 2 | 7.27 milligram per deciliter (mg/dL) | Standard Deviation 25.844 |
| Placebo | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 4 | 5.42 milligram per deciliter (mg/dL) | Standard Deviation 33.198 |
| Placebo | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 16 | 3.42 milligram per deciliter (mg/dL) | Standard Deviation 40.723 |
| PF-06835919 150 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 8 | -2.40 milligram per deciliter (mg/dL) | Standard Deviation 51.102 |
| PF-06835919 150 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 2 | 0.88 milligram per deciliter (mg/dL) | Standard Deviation 32.783 |
| PF-06835919 150 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 4 | -7.41 milligram per deciliter (mg/dL) | Standard Deviation 39.87 |
| PF-06835919 150 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 12 | -6.45 milligram per deciliter (mg/dL) | Standard Deviation 47.793 |
| PF-06835919 150 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 16 | -4.17 milligram per deciliter (mg/dL) | Standard Deviation 43.868 |
| PF-06835919 300 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 16 | -10.69 milligram per deciliter (mg/dL) | Standard Deviation 56.683 |
| PF-06835919 300 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 12 | -12.02 milligram per deciliter (mg/dL) | Standard Deviation 45.748 |
| PF-06835919 300 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 2 | -6.35 milligram per deciliter (mg/dL) | Standard Deviation 42.66 |
| PF-06835919 300 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 8 | -2.87 milligram per deciliter (mg/dL) | Standard Deviation 55.355 |
| PF-06835919 300 mg | Change From Baseline in Fasting Glucose Over 16 Weeks | Week 4 | -4.47 milligram per deciliter (mg/dL) | Standard Deviation 41.63 |
Secondary
Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks
HOMA-IR values were derived from fasting plasma insulin and glucose values. Greater reduction from baseline in HOMA-IR scale values shows greater effects on glycemic metabolism.
Time frame: From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Population: The FAS included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants who were in the FAS and had the HOMA-IR values at each timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 12 | 1.84 HOMA-IR scale | Standard Deviation 6.045 |
| Placebo | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 8 | 1.32 HOMA-IR scale | Standard Deviation 5.161 |
| Placebo | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 2 | 1.09 HOMA-IR scale | Standard Deviation 4.573 |
| Placebo | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 4 | 1.28 HOMA-IR scale | Standard Deviation 5.455 |
| Placebo | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 16 | 0.82 HOMA-IR scale | Standard Deviation 3.768 |
| PF-06835919 150 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 8 | 2.94 HOMA-IR scale | Standard Deviation 11.062 |
| PF-06835919 150 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 2 | 2.17 HOMA-IR scale | Standard Deviation 12.473 |
| PF-06835919 150 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 4 | 0.02 HOMA-IR scale | Standard Deviation 5.452 |
| PF-06835919 150 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 12 | 8.92 HOMA-IR scale | Standard Deviation 63.895 |
| PF-06835919 150 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 16 | 8.26 HOMA-IR scale | Standard Deviation 45.267 |
| PF-06835919 300 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 16 | 3.45 HOMA-IR scale | Standard Deviation 29.22 |
| PF-06835919 300 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 12 | 0.98 HOMA-IR scale | Standard Deviation 7.778 |
| PF-06835919 300 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 2 | 0.36 HOMA-IR scale | Standard Deviation 6.318 |
| PF-06835919 300 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 8 | -0.49 HOMA-IR scale | Standard Deviation 6.683 |
| PF-06835919 300 mg | Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks | Week 4 | -1.04 HOMA-IR scale | Standard Deviation 4.407 |
Secondary
Change From Baseline in Fasting Insulin Over 16 Weeks
A sufficient amount of blood was collected for the analysis of plasma insulin. The unit of insulin is milli-international units per liter (mIU/L).
Time frame: From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Population: The FAS included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants who were in the FAS and had the insulin values at each timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 2 | 1.79 mIU/L | Standard Deviation 9.275 |
| Placebo | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 12 | 3.00 mIU/L | Standard Deviation 13.202 |
| Placebo | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 8 | 2.56 mIU/L | Standard Deviation 12.617 |
| Placebo | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 16 | 1.99 mIU/L | Standard Deviation 8.862 |
| Placebo | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 4 | 2.22 mIU/L | Standard Deviation 12.723 |
| PF-06835919 150 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 8 | 13.01 mIU/L | Standard Deviation 63.009 |
| PF-06835919 150 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 2 | 2.94 mIU/L | Standard Deviation 14.375 |
| PF-06835919 150 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 4 | 1.65 mIU/L | Standard Deviation 20.118 |
| PF-06835919 150 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 12 | 9.70 mIU/L | Standard Deviation 65.593 |
| PF-06835919 150 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 16 | 17.94 mIU/L | Standard Deviation 101.553 |
| PF-06835919 300 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 16 | 4.84 mIU/L | Standard Deviation 39.099 |
| PF-06835919 300 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 12 | 3.52 mIU/L | Standard Deviation 19.148 |
| PF-06835919 300 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 2 | 1.53 mIU/L | Standard Deviation 16.837 |
| PF-06835919 300 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 8 | -0.45 mIU/L | Standard Deviation 16.336 |
| PF-06835919 300 mg | Change From Baseline in Fasting Insulin Over 16 Weeks | Week 4 | -2.47 mIU/L | Standard Deviation 10.672 |
Secondary
Change From Baseline in HbA1c at All Timepoints Other Than Week 16
A sufficient amount of blood was collected for the analysis of plasma HbA1c.
Time frame: From Baseline to Week 2, Week, 4, Week 8, and Week 12.
Population: The FAS included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants who were in the FAS and had the HbA1c values at each timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 2 | -0.14 Percent of HbA1c | Standard Deviation 0.626 |
| Placebo | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 4 | -0.09 Percent of HbA1c | Standard Deviation 0.428 |
| Placebo | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 8 | -0.11 Percent of HbA1c | Standard Deviation 0.588 |
| Placebo | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 12 | -0.12 Percent of HbA1c | Standard Deviation 0.816 |
| PF-06835919 150 mg | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 12 | -0.15 Percent of HbA1c | Standard Deviation 0.748 |
| PF-06835919 150 mg | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 2 | -0.11 Percent of HbA1c | Standard Deviation 0.592 |
| PF-06835919 150 mg | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 8 | -0.22 Percent of HbA1c | Standard Deviation 0.698 |
| PF-06835919 150 mg | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 4 | -0.17 Percent of HbA1c | Standard Deviation 0.633 |
| PF-06835919 300 mg | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 12 | -0.28 Percent of HbA1c | Standard Deviation 0.681 |
| PF-06835919 300 mg | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 4 | -0.21 Percent of HbA1c | Standard Deviation 0.357 |
| PF-06835919 300 mg | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 8 | -0.27 Percent of HbA1c | Standard Deviation 0.588 |
| PF-06835919 300 mg | Change From Baseline in HbA1c at All Timepoints Other Than Week 16 | Week 2 | -0.07 Percent of HbA1c | Standard Deviation 0.256 |
Secondary
Cumulative Number of Participants With Clinical Laboratory Abnormalities
Clinical laboratory tests included hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy). The abnormality criteria were standard sponsor reporting criteria.
Time frame: Up to 21 weeks.
Population: The safety analysis set included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants with evaluable laboratory values were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Cumulative Number of Participants With Clinical Laboratory Abnormalities | 52 Participants |
| PF-06835919 150 mg | Cumulative Number of Participants With Clinical Laboratory Abnormalities | 52 Participants |
| PF-06835919 300 mg | Cumulative Number of Participants With Clinical Laboratory Abnormalities | 51 Participants |
Secondary
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria
ECG data meeting the following criteria were reported: PR interval value \>=300 msec, QRS interval percent change \>= 50%, QTcF interval value \>450 msec and \<=480 msec, or change \>30 msec and \<=60 msec, or change \>60 msec.
Time frame: Up to 21 weeks.
Population: The safety analysis set included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants with evaluable ECG data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval change >30 msec and <=60 msec | 1 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval value >450 msec and <= 480 msec | 3 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | PR interval value >= 300 msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QRS interval percent change >= 50% | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval change >60 msec | 1 Participants |
| PF-06835919 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval value >450 msec and <= 480 msec | 2 Participants |
| PF-06835919 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | PR interval value >= 300 msec | 1 Participants |
| PF-06835919 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QRS interval percent change >= 50% | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval change >30 msec and <=60 msec | 5 Participants |
| PF-06835919 150 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval change >60 msec | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval change >60 msec | 1 Participants |
| PF-06835919 300 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval change >30 msec and <=60 msec | 1 Participants |
| PF-06835919 300 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | PR interval value >= 300 msec | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QTcF interval value >450 msec and <= 480 msec | 2 Participants |
| PF-06835919 300 mg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria | QRS interval percent change >= 50% | 1 Participants |
Secondary
Number of Participants With Hypoglycemia TEAEs
Hypoglycemic AEs were routinely monitored during participation in the study. Hypoglycemic AE was defined as 1 of the following: 1. Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemic AE but a plasma glucose value of \<70 milligram per deciliter (mg/dL) using glucometer; 2. Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemic AEs were accompanied with a glucose value of \<70 mg/dL using glucometer and the clinical picture included prompt resolution with food intake, subcutaneous glucagon or intravenous (IV) glucose; 3. Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemic AEs were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration of \<70 mg/dL, and the clinical picture included prompt resolution with food intake, subcutaneous glucagon, or IV glucose.
Time frame: Up to 21 weeks.
Population: The safety analysis set included all participants randomly assigned to treatment and who took at least 1 dose of treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Hypoglycemia TEAEs | Asymptomatic hypoglycemia | 1 Participants |
| Placebo | Number of Participants With Hypoglycemia TEAEs | Severe hypoglycemia | 0 Participants |
| Placebo | Number of Participants With Hypoglycemia TEAEs | Documented symptomatic hypoglycemia | 0 Participants |
| Placebo | Number of Participants With Hypoglycemia TEAEs | Probable symptomatic hypoglycemia | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Hypoglycemia TEAEs | Probable symptomatic hypoglycemia | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Hypoglycemia TEAEs | Asymptomatic hypoglycemia | 1 Participants |
| PF-06835919 150 mg | Number of Participants With Hypoglycemia TEAEs | Documented symptomatic hypoglycemia | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Hypoglycemia TEAEs | Severe hypoglycemia | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Hypoglycemia TEAEs | Probable symptomatic hypoglycemia | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Hypoglycemia TEAEs | Severe hypoglycemia | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Hypoglycemia TEAEs | Documented symptomatic hypoglycemia | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Hypoglycemia TEAEs | Asymptomatic hypoglycemia | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or that was considered to be an important medical event. An AE was considered TEAE if the event occurred during the on-treatment period. The causality of AEs were assessed by the investigator using clinical judgement. A severe AE was an event that prevents normal everyday activities.
Time frame: Up to 21 weeks.
Population: The safety analysis set included all participants randomly assigned to treatment and who took at least 1 dose of treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Treatment-related TEAEs | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued from study due to All-causality TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality Severe TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality TEAEs | 22 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with dose reductions or temporary discontinuation due to All-causality TEAEs | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued study drug due to All-causality TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality Serious TEAEs | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality Severe TEAEs | 2 Participants |
| PF-06835919 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality TEAEs | 25 Participants |
| PF-06835919 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Treatment-related TEAEs | 4 Participants |
| PF-06835919 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality Serious TEAEs | 1 Participants |
| PF-06835919 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued from study due to All-causality TEAEs | 1 Participants |
| PF-06835919 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued study drug due to All-causality TEAEs | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with dose reductions or temporary discontinuation due to All-causality TEAEs | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued from study due to All-causality TEAEs | 1 Participants |
| PF-06835919 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with Treatment-related TEAEs | 1 Participants |
| PF-06835919 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with dose reductions or temporary discontinuation due to All-causality TEAEs | 1 Participants |
| PF-06835919 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued study drug due to All-causality TEAEs | 1 Participants |
| PF-06835919 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality Severe TEAEs | 1 Participants |
| PF-06835919 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality Serious TEAEs | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with All-causality TEAEs | 18 Participants |
Secondary
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria
Vital signs data meeting the following criteria were reported: sitting diastolic blood pressure (DBP) \<50 mmHg or \>= 20 mmHg increase or \>= 20 mmHg decrease, sitting systolic blood pressure (SBP) blood pressure \<90 mmHg or \>=30 mmHg increase or \>=30 mmHg decrease.
Time frame: Up to 21 weeks.
Population: The safety analysis set included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants with evaluable vital signs data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP value <50 mmHg | 1 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP change >= 20 mmHg increase | 3 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP change >=20 mmHg decrease | 3 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP value <90 mmHg | 1 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP change >= 30 mmHg increase | 3 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP change >=30 mmHg decrease | 5 Participants |
| PF-06835919 150 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP change >=30 mmHg decrease | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP value <50 mmHg | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP value <90 mmHg | 0 Participants |
| PF-06835919 150 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP change >= 30 mmHg increase | 1 Participants |
| PF-06835919 150 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP change >= 20 mmHg increase | 3 Participants |
| PF-06835919 150 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP change >=20 mmHg decrease | 1 Participants |
| PF-06835919 300 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP change >= 20 mmHg increase | 2 Participants |
| PF-06835919 300 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP change >=20 mmHg decrease | 2 Participants |
| PF-06835919 300 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP change >=30 mmHg decrease | 2 Participants |
| PF-06835919 300 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP value <90 mmHg | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | DBP value <50 mmHg | 0 Participants |
| PF-06835919 300 mg | Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria | SBP change >= 30 mmHg increase | 4 Participants |
Secondary
Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks
ALT was assessed as one of the clinical laboratory chemistry tests.
Time frame: From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Population: The FAS included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants who were in the FAS and had the ALT values at each timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 2 | 2.4 Percent change | Standard Deviation 34.69 |
| Placebo | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 12 | -3.4 Percent change | Standard Deviation 32.14 |
| Placebo | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 8 | 6.7 Percent change | Standard Deviation 63.32 |
| Placebo | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 16 | 20.4 Percent change | Standard Deviation 78.74 |
| Placebo | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 4 | 2.3 Percent change | Standard Deviation 29.13 |
| PF-06835919 150 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 8 | -6.3 Percent change | Standard Deviation 23.72 |
| PF-06835919 150 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 2 | -8.8 Percent change | Standard Deviation 20.43 |
| PF-06835919 150 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 4 | -4.1 Percent change | Standard Deviation 29.51 |
| PF-06835919 150 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 12 | -7.9 Percent change | Standard Deviation 29.01 |
| PF-06835919 150 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 16 | -7.8 Percent change | Standard Deviation 29.36 |
| PF-06835919 300 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 16 | -9.8 Percent change | Standard Deviation 25.89 |
| PF-06835919 300 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 12 | -10.7 Percent change | Standard Deviation 23.96 |
| PF-06835919 300 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 2 | -6.0 Percent change | Standard Deviation 22.36 |
| PF-06835919 300 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 8 | -10.5 Percent change | Standard Deviation 29.16 |
| PF-06835919 300 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks | Week 4 | -5.4 Percent change | Standard Deviation 27.86 |
Secondary
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks
Blood samples were collected to ensure sufficient serum for the analysis of hs-CRP.
Time frame: From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Population: The FAS included all participants randomly assigned to treatment and who took at least 1 dose of treatment. Participants who were in the FAS and had the hs-CRP values at each timepoint were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 12 | 31.29 Percent change | Standard Deviation 86.516 |
| Placebo | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 8 | 93.82 Percent change | Standard Deviation 446.72 |
| Placebo | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 2 | 40.26 Percent change | Standard Deviation 129.051 |
| Placebo | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 4 | 50.64 Percent change | Standard Deviation 195.742 |
| Placebo | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 16 | 102.16 Percent change | Standard Deviation 449.453 |
| PF-06835919 150 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 8 | 13.09 Percent change | Standard Deviation 62.564 |
| PF-06835919 150 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 2 | 19.11 Percent change | Standard Deviation 85.912 |
| PF-06835919 150 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 4 | 38.46 Percent change | Standard Deviation 185.938 |
| PF-06835919 150 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 12 | 14.99 Percent change | Standard Deviation 62.415 |
| PF-06835919 150 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 16 | 9.37 Percent change | Standard Deviation 57.144 |
| PF-06835919 300 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 16 | 7.11 Percent change | Standard Deviation 109.031 |
| PF-06835919 300 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 12 | -9.68 Percent change | Standard Deviation 90.926 |
| PF-06835919 300 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 2 | 17.50 Percent change | Standard Deviation 159.122 |
| PF-06835919 300 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 8 | -17.23 Percent change | Standard Deviation 51.612 |
| PF-06835919 300 mg | Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks | Week 4 | -18.25 Percent change | Standard Deviation 41.961 |