Diabetic Nephropathy
Conditions
Keywords
Diabetic nephropathy, type 2 diabetes, albuminuria, chemokine antagonist
Brief summary
The study hypothesis under test is that administration of a CCR2/5 antagonist to subjects with type 2 diabetes and overt nephropathy will result in a reduction in urinary albumin, a surrogate for improved glomerular filtration.
Interventions
DRUGPF-04634817
Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function
DRUGPlacebo
Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of type 2 diabetes together with stages 2, 3a, 3b or 4 CKD, based on an eGFR of 20-75 mL/min/1.73m2. * Evidence of persistent, overt albuminuria; defined as a UACR \>=300 mg/g (\>=33.9 mg/mmol) or UPCR \>=390 mg/g (44.1 mg/mmol), or equivalent, for 3 months or longer. * Stable background therapy of RAAS inhibition (ie, an ACE inhibitor and/or an ARB, which may also include an aldosterone antagonist in double RAAS but not triple RAAS inhibitor therapy) for at least 3 months before screening and to be maintained for the duration of the study.
Exclusion criteria
* Subjects with CKD resulting from type 1 diabetes or non-diabetic CKD. * Subjects who are diagnosed with autosomal dominant polycystic kidney disease (ADPCKD), severe peripheral vascular disease (PVD) or obstructive uropathy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 | Baseline and Week 12 | The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in UACR at Weeks 4, 8 and 16 | Baseline, Weeks 4, 8 and 16 | The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. |
| Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 | Baseline, Week 12, and Week 16 | Serum cystatin C may be a more reliable endogenous marker of GFR than serum creatinine. eGFR was calculated using the Cystatin Formula and normalized to 1.73 m\^2 body surface area. |
| Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Baseline, Weeks 4, 8, 12 and 16 | The presence of protein in the urine (proteinuria) often implies kidney disease. Protein and creatinine concentrations were obtained from spot urine samples. |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Baseline, Week 1, 4, 8, 12 and 16 | eGFR was calculated using the MDRD equation and normalized to 1.73 m\^2 body surface area. Age and corresponding creatinine at each visit (Weeks 1, 4, 8, 12 and 16) were used to calculate GFR |
| Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Baseline, Week 1, 4, 8, 12 and 16 | Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent. Change from baseline=creatinine level at Week 1, 4, 8, 12 or 16 minus baseline level where higher scores represented decreased kidney function. |
| Change From Baseline in Serum Cystatin C at Weeks 12 and 16 | Baseline, Week 12, and Week 16 | Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise. |
| Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Baseline, Weeks 4, 8, 12 and 16 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. As the average amount of plasma glucose increases, the fraction of HbA1c increases in a predictable way. |
| Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | 1, 2, 4 hours post-dose on Day 1; 2 hours post-dose on Weeks 1, 4, 8 and 12 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Baseline, Weeks 1, 4, 8, 12 and 16 | — |
| Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern | Baseline up to Week 16 (follow-up visit) | The following laboratory parameters were analyzed for abnormalities at any time point mentioned in the timeframe: clinical chemistry (sodium, potassium, chloride, bicarbonate, phosphate, glucose, blood urea nitrogen \[BUN\], creatinine, albumin, calcium, bilirubin \[total, direct, and indirect\], gamma-glutamyl transferase \[GGT\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], lactic dehydrogenase \[LDH\], alkaline phosphatase, creatine phosphokinase \[CPK\], uric acid, amylase and lipase); hematology (hemoglobin, hematocrit, red blood cell \[RBC\] count, white blood cell \[WBC\] count with differential, and platelet count); FSH (for postmenopausal women who had been amenorrheic for less than 2 years prior to screening). |
| Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Baseline, Weeks 1, 4 and 12 | Criteria for potentially clinically important ECG values were defined as: PR interval \>=300 milliseconds (msec) or \>=25%/50% increase when baseline is \>200 msec and ≥50% increase when baseline is less than or equal to (\<=)200 msec; QRS interval \>=140 msec or \>=50% increase from baseline (IFB); QTc \>=450 msec or \>=30 msec increase; corrected QT interval using Fridericia's formula (QTcF) \>=450 msec or \>=30 msec increase. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Baseline up to 28 days after last study drug administration | An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. A 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 are events between first dose of treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs. |
| Number of Participants With Increased Fasting Blood Glucose | Baseline up to Week 16 (follow-up visit) | — |
| Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Baseline, Weeks 1, 4, 8, 12 and 16 | — |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Baseline, Weeks 1, 4, 8, 12 and 16 | — |
Countries
Argentina, Australia, Canada, Germany, Hong Kong, Italy, Malaysia, Peru, Poland, Puerto Rico, Romania, South Korea, Spain, United States
Participant flow
Pre-assignment details
The primary entry criterion for participants was based on presence of macroalbuminuria (urine albumin to creatinine ratio \[UACR\] greater than or equal to (\>=)300 milligrams per gram (mg/g).
Participants by arm
| Arm | Count |
|---|---|
| PF-04634817 200 mg/150 mg Participants were dosed orally at 150 mg (eGFR 20-\<30 mL/min/1.73 m\^2) or 200 mg (30-75 mL/min/1.73 m\^2) QD for 12 weeks. | 170 |
| Placebo Participants were dosed orally with matching placebo tablets QD for 12 weeks. | 56 |
| Total | 226 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 9 | 5 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Did Not Meet Entrance Criteria | 4 | 6 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Medication Error Without Associated AE | 0 | 1 | 0 |
| Overall Study | Other | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 7 | 1 |
Baseline characteristics
| Characteristic | PF-04634817 200 mg/150 mg | Total | Placebo |
|---|---|---|---|
| Age, Customized 18-44 years | 3 participants | 3 participants | 0 participants |
| Age, Customized 45-64 years | 78 participants | 109 participants | 31 participants |
| Age, Customized >=65 years | 89 participants | 114 participants | 25 participants |
| Age, Customized Less than (<) 18 years | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 36 Participants | 43 Participants | 7 Participants |
| Sex: Female, Male Male | 134 Participants | 183 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 30 | 40 / 140 | 15 / 56 |
| serious Total, serious adverse events | 6 / 30 | 11 / 140 | 5 / 56 |
Outcome results
Primary
Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12
The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.
Time frame: Baseline and Week 12
Population: The Full Analysis Set (FAS) was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-04634817 200 mg/150 mg | Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 | 13.27 percent (%) | 95% Confidence Interval 5.43 |
| Placebo | Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 | 5.02 percent (%) | 95% Confidence Interval 6.87 |
95% CI: [0.75, 1.09]ANCOVA
Secondary
Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16
Serum cystatin C may be a more reliable endogenous marker of GFR than serum creatinine. eGFR was calculated using the Cystatin Formula and normalized to 1.73 m\^2 body surface area.
Time frame: Baseline, Week 12, and Week 16
Population: The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 | Baseline (n=159,50) | 45.28 mL/min/1.73m^2 | Standard Deviation 14.22 |
| PF-04634817 200 mg/150 mg | Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 | Change From Baseline at Week 12 (n=135,44) | -1.10 mL/min/1.73m^2 | Standard Deviation 6.3 |
| PF-04634817 200 mg/150 mg | Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 | Change From Baseline at Week 16 (n=134,43) | -2.27 mL/min/1.73m^2 | Standard Deviation 6.77 |
| Placebo | Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 | Baseline (n=159,50) | 45.36 mL/min/1.73m^2 | Standard Deviation 14.94 |
| Placebo | Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 | Change From Baseline at Week 12 (n=135,44) | -0.70 mL/min/1.73m^2 | Standard Deviation 5.49 |
| Placebo | Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 | Change From Baseline at Week 16 (n=134,43) | -0.91 mL/min/1.73m^2 | Standard Deviation 6.3 |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16
eGFR was calculated using the MDRD equation and normalized to 1.73 m\^2 body surface area. Age and corresponding creatinine at each visit (Weeks 1, 4, 8, 12 and 16) were used to calculate GFR
Time frame: Baseline, Week 1, 4, 8, 12 and 16
Population: The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 1 (n=157,50) | -0.77 mL/min/1.73m^2 | Standard Deviation 5.8 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=147,47) | -1.60 mL/min/1.73m^2 | Standard Deviation 5.34 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=136,45) | -1.14 mL/min/1.73m^2 | Standard Deviation 5.7 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Baseline (n=159,51) | 41.80 mL/min/1.73m^2 | Standard Deviation 12.18 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=134,44) | -2.14 mL/min/1.73m^2 | Standard Deviation 6.42 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=157,51) | -1.07 mL/min/1.73m^2 | Standard Deviation 5.37 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=134,44) | -1.18 mL/min/1.73m^2 | Standard Deviation 5.58 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Baseline (n=159,51) | 41.65 mL/min/1.73m^2 | Standard Deviation 13.46 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 1 (n=157,50) | -0.35 mL/min/1.73m^2 | Standard Deviation 5.28 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=157,51) | -1.32 mL/min/1.73m^2 | Standard Deviation 5.12 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=136,45) | -1.03 mL/min/1.73m^2 | Standard Deviation 5.75 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=147,47) | -2.15 mL/min/1.73m^2 | Standard Deviation 6.83 |
Secondary
Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. As the average amount of plasma glucose increases, the fraction of HbA1c increases in a predictable way.
Time frame: Baseline, Weeks 4, 8, 12 and 16
Population: The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=137,44) | -0.01 percent | Standard Deviation 0.76 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Baseline (n=159,51) | 7.51 percent | Standard Deviation 1.22 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=157,51) | 0.03 percent | Standard Deviation 0.46 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=147,46) | -0.02 percent | Standard Deviation 0.64 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=133,44) | 0.04 percent | Standard Deviation 0.89 |
| Placebo | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=133,44) | -0.04 percent | Standard Deviation 1.13 |
| Placebo | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=147,46) | -0.08 percent | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Baseline (n=159,51) | 7.91 percent | Standard Deviation 1.42 |
| Placebo | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=137,44) | -0.06 percent | Standard Deviation 0.81 |
| Placebo | Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=157,51) | -0.04 percent | Standard Deviation 0.46 |
Secondary
Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16
Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent. Change from baseline=creatinine level at Week 1, 4, 8, 12 or 16 minus baseline level where higher scores represented decreased kidney function.
Time frame: Baseline, Week 1, 4, 8, 12 and 16
Population: The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Baseline (n=159,51) | 1.72 milligrams per deciliter (mg/dL) | Standard Deviation 0.51 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 1 (n=158,50) | 0.05 milligrams per deciliter (mg/dL) | Standard Deviation 0.22 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=157,51) | 0.06 milligrams per deciliter (mg/dL) | Standard Deviation 0.21 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=147,47) | 0.06 milligrams per deciliter (mg/dL) | Standard Deviation 0.21 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=137,45) | 0.05 milligrams per deciliter (mg/dL) | Standard Deviation 0.24 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=134,44) | 0.09 milligrams per deciliter (mg/dL) | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=137,45) | 0.08 milligrams per deciliter (mg/dL) | Standard Deviation 0.2 |
| Placebo | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Baseline (n=159,51) | 1.77 milligrams per deciliter (mg/dL) | Standard Deviation 0.51 |
| Placebo | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=147,47) | 0.09 milligrams per deciliter (mg/dL) | Standard Deviation 0.24 |
| Placebo | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 1 (n=158,50) | 0.03 milligrams per deciliter (mg/dL) | Standard Deviation 0.17 |
| Placebo | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=134,44) | 0.09 milligrams per deciliter (mg/dL) | Standard Deviation 0.29 |
| Placebo | Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=157,51) | 0.11 milligrams per deciliter (mg/dL) | Standard Deviation 0.3 |
Secondary
Change From Baseline in Serum Cystatin C at Weeks 12 and 16
Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise.
Time frame: Baseline, Week 12, and Week 16
Population: The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Cystatin C at Weeks 12 and 16 | Baseline (n=159,51) | 1.54 mg/dL | Standard Deviation 0.43 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Cystatin C at Weeks 12 and 16 | Change From Baseline at Week 12 (n=136,45) | 0.03 mg/dL | Standard Deviation 0.25 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Serum Cystatin C at Weeks 12 and 16 | Change From Baseline at Week 16 (n=134,44) | 0.05 mg/dL | Standard Deviation 0.26 |
| Placebo | Change From Baseline in Serum Cystatin C at Weeks 12 and 16 | Baseline (n=159,51) | 1.52 mg/dL | Standard Deviation 0.41 |
| Placebo | Change From Baseline in Serum Cystatin C at Weeks 12 and 16 | Change From Baseline at Week 12 (n=136,45) | 0.03 mg/dL | Standard Deviation 0.21 |
| Placebo | Change From Baseline in Serum Cystatin C at Weeks 12 and 16 | Change From Baseline at Week 16 (n=134,44) | 0.06 mg/dL | Standard Deviation 0.25 |
Secondary
Change From Baseline in UACR at Weeks 4, 8 and 16
The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.
Time frame: Baseline, Weeks 4, 8 and 16
Population: The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in UACR at Weeks 4, 8 and 16 | Baseline (n=157,50) | 127.41 mg/millimolar creatinine (mmolCr) | Geometric Coefficient of Variation 96 |
| PF-04634817 200 mg/150 mg | Change From Baseline in UACR at Weeks 4, 8 and 16 | Change From Baseline at Week 4 (n=148,46) | 0.89 mg/millimolar creatinine (mmolCr) | Geometric Coefficient of Variation 66 |
| PF-04634817 200 mg/150 mg | Change From Baseline in UACR at Weeks 4, 8 and 16 | Change From Baseline at Week 8 (n=134,43) | 0.90 mg/millimolar creatinine (mmolCr) | Geometric Coefficient of Variation 62 |
| PF-04634817 200 mg/150 mg | Change From Baseline in UACR at Weeks 4, 8 and 16 | Change From Baseline at Week 16 (n=126,37) | 0.93 mg/millimolar creatinine (mmolCr) | Geometric Coefficient of Variation 72 |
| Placebo | Change From Baseline in UACR at Weeks 4, 8 and 16 | Change From Baseline at Week 16 (n=126,37) | 0.92 mg/millimolar creatinine (mmolCr) | Geometric Coefficient of Variation 56 |
| Placebo | Change From Baseline in UACR at Weeks 4, 8 and 16 | Baseline (n=157,50) | 121.80 mg/millimolar creatinine (mmolCr) | Geometric Coefficient of Variation 88 |
| Placebo | Change From Baseline in UACR at Weeks 4, 8 and 16 | Change From Baseline at Week 8 (n=134,43) | 0.94 mg/millimolar creatinine (mmolCr) | Geometric Coefficient of Variation 57 |
| Placebo | Change From Baseline in UACR at Weeks 4, 8 and 16 | Change From Baseline at Week 4 (n=148,46) | 0.91 mg/millimolar creatinine (mmolCr) | Geometric Coefficient of Variation 88 |
Secondary
Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16
The presence of protein in the urine (proteinuria) often implies kidney disease. Protein and creatinine concentrations were obtained from spot urine samples.
Time frame: Baseline, Weeks 4, 8, 12 and 16
Population: The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Baseline (n=155,49) | 185.42 mg/mmolCr | Geometric Coefficient of Variation 97 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=125,42) | 0.92 mg/mmolCr | Geometric Coefficient of Variation 58 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=130,42) | 0.92 mg/mmolCr | Geometric Coefficient of Variation 50 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=125,36) | 0.95 mg/mmolCr | Geometric Coefficient of Variation 58 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=143,45) | 0.93 mg/mmolCr | Geometric Coefficient of Variation 47 |
| Placebo | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=125,36) | 0.92 mg/mmolCr | Geometric Coefficient of Variation 55 |
| Placebo | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=143,45) | 0.92 mg/mmolCr | Geometric Coefficient of Variation 76 |
| Placebo | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Baseline (n=155,49) | 176.31 mg/mmolCr | Geometric Coefficient of Variation 82 |
| Placebo | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=130,42) | 0.94 mg/mmolCr | Geometric Coefficient of Variation 46 |
| Placebo | Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=125,42) | 0.92 mg/mmolCr | Geometric Coefficient of Variation 79 |
Secondary
Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12
Time frame: 1, 2, 4 hours post-dose on Day 1; 2 hours post-dose on Weeks 1, 4, 8 and 12
Population: The PK Concentration Analysis Set is defined as all participants in the FAS for whom a PK sample was obtained and analyzed; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Day 1: 1 Hour Post-Dose (n=29,124) | 434.5 ng/mL | Geometric Coefficient of Variation 65 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Day 1: 2 Hours Post-Dose (n=30,139) | 579.3 ng/mL | Geometric Coefficient of Variation 37 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Day 1: 4 Hours Post-Dose (n=29,137) | 497.4 ng/mL | Geometric Coefficient of Variation 38 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 1: Pre-Dose (n=28,131) | 294.4 ng/mL | Geometric Coefficient of Variation 60 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 1: 2 Hours Post-Dose (n=28,132) | 884.8 ng/mL | Geometric Coefficient of Variation 42 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 4: Pre-Dose (n=25,126) | 231.3 ng/mL | Geometric Coefficient of Variation 51 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 4: 2 Hours Post-Dose (n=24,122) | 785.8 ng/mL | Geometric Coefficient of Variation 45 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 8: Pre-Dose (n=23,113) | 310.2 ng/mL | Geometric Coefficient of Variation 79 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 8: 2 Hours Post-Dose (n=23,114) | 730.0 ng/mL | Geometric Coefficient of Variation 70 |
| PF-04634817 200 mg/150 mg | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 12 (n=20,113) | 320.1 ng/mL | Geometric Coefficient of Variation 75 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 8: Pre-Dose (n=23,113) | 245.2 ng/mL | Geometric Coefficient of Variation 77 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Day 1: 1 Hour Post-Dose (n=29,124) | 524.4 ng/mL | Geometric Coefficient of Variation 83 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 4: Pre-Dose (n=25,126) | 239.5 ng/mL | Geometric Coefficient of Variation 87 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Day 1: 2 Hours Post-Dose (n=30,139) | 602.9 ng/mL | Geometric Coefficient of Variation 52 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 12 (n=20,113) | 252.3 ng/mL | Geometric Coefficient of Variation 84 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Day 1: 4 Hours Post-Dose (n=29,137) | 547.7 ng/mL | Geometric Coefficient of Variation 46 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 4: 2 Hours Post-Dose (n=24,122) | 918 ng/mL | Geometric Coefficient of Variation 55 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 1: Pre-Dose (n=28,131) | 231.2 ng/mL | Geometric Coefficient of Variation 73 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 8: 2 Hours Post-Dose (n=23,114) | 895 ng/mL | Geometric Coefficient of Variation 57 |
| Placebo | Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 | Week 1: 2 Hours Post-Dose (n=28,132) | 865.0 ng/mL | Geometric Coefficient of Variation 55 |
Other Pre-specified
Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16
Time frame: Baseline, Weeks 1, 4, 8, 12 and 16
Population: The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Baseline (n=167,53) | 93.8 kilograms (kg) | Standard Deviation 23.97 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 1 (n=163,53) | 0.0 kilograms (kg) | Standard Deviation 1.03 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=153,49) | -0.0 kilograms (kg) | Standard Deviation 1.74 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=141,47) | 0.1 kilograms (kg) | Standard Deviation 2.45 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=134,45) | 0.3 kilograms (kg) | Standard Deviation 2.66 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=137,45) | -0.1 kilograms (kg) | Standard Deviation 2.79 |
| Placebo | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=134,45) | 0.7 kilograms (kg) | Standard Deviation 3.02 |
| Placebo | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Baseline (n=167,53) | 95.1 kilograms (kg) | Standard Deviation 25.95 |
| Placebo | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=141,47) | 0.7 kilograms (kg) | Standard Deviation 2.74 |
| Placebo | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 1 (n=163,53) | 0.3 kilograms (kg) | Standard Deviation 1.42 |
| Placebo | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=137,45) | 0.2 kilograms (kg) | Standard Deviation 3.37 |
| Placebo | Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=153,49) | 0.4 kilograms (kg) | Standard Deviation 3.29 |
Other Pre-specified
Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16
Time frame: Baseline, Weeks 1, 4, 8, 12 and 16
Population: The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Baseline (n=168,53) | 68.7 beats per minute (bpm) | Standard Deviation 9.74 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 1 (n=164,53) | 0.1 beats per minute (bpm) | Standard Deviation 5.86 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=154,49) | 0.3 beats per minute (bpm) | Standard Deviation 6.01 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=142,47) | 0.2 beats per minute (bpm) | Standard Deviation 6.54 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=134,45) | 0.2 beats per minute (bpm) | Standard Deviation 7.03 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=138,45) | 1.4 beats per minute (bpm) | Standard Deviation 8.22 |
| Placebo | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 12 (n=134,45) | 0.5 beats per minute (bpm) | Standard Deviation 7.33 |
| Placebo | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Baseline (n=168,53) | 69.3 beats per minute (bpm) | Standard Deviation 9.3 |
| Placebo | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 8 (n=142,47) | 1.4 beats per minute (bpm) | Standard Deviation 6.77 |
| Placebo | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 1 (n=164,53) | -0.7 beats per minute (bpm) | Standard Deviation 5.63 |
| Placebo | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 16 (n=138,45) | -0.1 beats per minute (bpm) | Standard Deviation 6.92 |
| Placebo | Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 | Change From Baseline at Week 4 (n=154,49) | -1.0 beats per minute (bpm) | Standard Deviation 6.63 |
Other Pre-specified
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16
Time frame: Baseline, Weeks 1, 4, 8, 12 and 16
Population: The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP: Baseline (n=168,53) | 140.4 millimeters of mercury (mm Hg) | Standard Deviation 13.96 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 1 (n=164,53) | -0.8 millimeters of mercury (mm Hg) | Standard Deviation 12.75 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 4 (n=154,49) | -0.5 millimeters of mercury (mm Hg) | Standard Deviation 15.43 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 8 (n=142,47) | -3.4 millimeters of mercury (mm Hg) | Standard Deviation 12.94 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 12 (n=134,45) | -2.0 millimeters of mercury (mm Hg) | Standard Deviation 13.28 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 16 (n=138,45) | -2.4 millimeters of mercury (mm Hg) | Standard Deviation 15.14 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP: Baseline (n=168,53) | 75.9 millimeters of mercury (mm Hg) | Standard Deviation 8.97 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 1 (n=164,53) | -0.2 millimeters of mercury (mm Hg) | Standard Deviation 6.94 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 4 (n=154,49) | 0.1 millimeters of mercury (mm Hg) | Standard Deviation 8.23 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 8 (n=142,47) | -1.9 millimeters of mercury (mm Hg) | Standard Deviation 7.46 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 12 (n=134,45) | -0.9 millimeters of mercury (mm Hg) | Standard Deviation 6.88 |
| PF-04634817 200 mg/150 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 16 (n=138,45) | -1.7 millimeters of mercury (mm Hg) | Standard Deviation 7.98 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 12 (n=134,45) | -0.2 millimeters of mercury (mm Hg) | Standard Deviation 6.69 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP: Baseline (n=168,53) | 139.9 millimeters of mercury (mm Hg) | Standard Deviation 13.6 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP: Baseline (n=168,53) | 77.1 millimeters of mercury (mm Hg) | Standard Deviation 6.88 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 1 (n=164,53) | -1.6 millimeters of mercury (mm Hg) | Standard Deviation 12.87 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 8 (n=142,47) | -1.5 millimeters of mercury (mm Hg) | Standard Deviation 7.05 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 4 (n=154,49) | -1.6 millimeters of mercury (mm Hg) | Standard Deviation 14.19 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 1 (n=164,53) | -2.7 millimeters of mercury (mm Hg) | Standard Deviation 7.58 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 8 (n=142,47) | -1.1 millimeters of mercury (mm Hg) | Standard Deviation 13.71 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 16 (n=138,45) | 0.9 millimeters of mercury (mm Hg) | Standard Deviation 8.4 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 12 (n=134,45) | -1.3 millimeters of mercury (mm Hg) | Standard Deviation 13.23 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine DBP:Change From Baseline Week 4 (n=154,49) | -1.8 millimeters of mercury (mm Hg) | Standard Deviation 7.47 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 | Supine SBP:Change From Baseline Week 16 (n=138,45) | -0.3 millimeters of mercury (mm Hg) | Standard Deviation 14.41 |
Other Pre-specified
Number of Participants With Increased Fasting Blood Glucose
Time frame: Baseline up to Week 16 (follow-up visit)
Population: The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; number of participants analyzed (N) is number of evaluable participants for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04634817 200 mg/150 mg | Number of Participants With Increased Fasting Blood Glucose | 1 participants |
| Placebo | Number of Participants With Increased Fasting Blood Glucose | 0 participants |
Other Pre-specified
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern
The following laboratory parameters were analyzed for abnormalities at any time point mentioned in the timeframe: clinical chemistry (sodium, potassium, chloride, bicarbonate, phosphate, glucose, blood urea nitrogen \[BUN\], creatinine, albumin, calcium, bilirubin \[total, direct, and indirect\], gamma-glutamyl transferase \[GGT\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], lactic dehydrogenase \[LDH\], alkaline phosphatase, creatine phosphokinase \[CPK\], uric acid, amylase and lipase); hematology (hemoglobin, hematocrit, red blood cell \[RBC\] count, white blood cell \[WBC\] count with differential, and platelet count); FSH (for postmenopausal women who had been amenorrheic for less than 2 years prior to screening).
Time frame: Baseline up to Week 16 (follow-up visit)
Population: The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; number of participants analyzed (N) is number of evaluable participants for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04634817 200 mg/150 mg | Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern | 154 participants |
| Placebo | Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern | 49 participants |
Other Pre-specified
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Criteria for potentially clinically important ECG values were defined as: PR interval \>=300 milliseconds (msec) or \>=25%/50% increase when baseline is \>200 msec and ≥50% increase when baseline is less than or equal to (\<=)200 msec; QRS interval \>=140 msec or \>=50% increase from baseline (IFB); QTc \>=450 msec or \>=30 msec increase; corrected QT interval using Fridericia's formula (QTcF) \>=450 msec or \>=30 msec increase.
Time frame: Baseline, Weeks 1, 4 and 12
Population: The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; n=number of participants analyzed in respective arms for category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum PR Interval >=300 msec (n=164,55) | 3 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTc Interval 480-<500 msec (n=169,56) | 4 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QRS Complex >=140 msec (n=169,56) | 2 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QT Interval >=500 msec (n=169,56) | 0 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTc Interval 450-<480 msec (n=169,56) | 23 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTc Interval >=500 msec (n=169,56) | 0 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTcF Interval 450-<480 msec (n=169,56) | 11 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTcF Interval 480-<500 msec (n=169,56) | 1 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTcF Interval >=500 msec (n=169,56) | 1 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | PR Interval >=25/50% IFB (n=163,53) | 3 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QRS Complex >=50% IFB (n=169,55) | 3 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTc Interval 30-<60 msec IFB (n=169,55) | 15 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTc Interval >=60 msec IFB (n=169,55) | 0 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 30-<60 msec IFB (n=169,55) | 8 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval >=60 msec IFB (n=169,55) | 1 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval >=60 msec IFB (n=169,55) | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTcF Interval 480-<500 msec (n=169,56) | 1 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | PR Interval >=25/50% IFB (n=163,53) | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum PR Interval >=300 msec (n=164,55) | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTc Interval 30-<60 msec IFB (n=169,55) | 4 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QRS Complex >=140 msec (n=169,56) | 1 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTcF Interval >=500 msec (n=169,56) | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QT Interval >=500 msec (n=169,56) | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 30-<60 msec IFB (n=169,55) | 3 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTc Interval 450-<480 msec (n=169,56) | 11 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTc Interval 480-<500 msec (n=169,56) | 1 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTc Interval >=60 msec IFB (n=169,55) | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTc Interval >=500 msec (n=169,56) | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QRS Complex >=50% IFB (n=169,55) | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | Maximum QTcF Interval 450-<480 msec (n=169,56) | 5 participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. A 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 are events between first dose of treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.
Time frame: Baseline up to 28 days after last study drug administration
Population: The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04634817 200 mg/150 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 106 participants |
| PF-04634817 200 mg/150 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 17 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 36 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 5 participants |