Renal Impairment
Conditions
Brief summary
This study is a phase 1 non-randomized, open-label, single-dose, parallel-group study of PF 04965842 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with moderate renal impairment (Part 2).
Detailed description
This is a Phase 1 non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-04965842 after a single 200 mg oral dose. Subjects will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: A total of approximately16 subjects will be enrolled; approximately 8 subjects with severe renal impairment and approximately 8 with normal renal function. After statistical evaluation of results from Part 1, Part 2 may be conducted and approximately 8 subjects with moderate renal impairment will be enrolled. The total duration of participation from the Screening Visit to Day 4 will be a maximum of 31 days and from the Screening Visit to Follow-up Contact/Visit will be a maximum of 67 days.
Interventions
DRUGPF-04965842
PF 04965842 is a janus kinase (JAK) 1 inhibitor that is currently being developed for the treatment of atopic dermatitis (AD).
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Part 1 will be conducted. The 8 subjects from the renal impaired group will be recruited before recruiting the 8 subjects without renal impairment function in Part 1. After statistical evaluation of results from Part 1, Part 2 may be conducted.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Breath alcohol test at Screening and Day -1 must be negative. * Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m2; and a total body weight \>50 kg (110 lb). Additional inclusion criteria for subjects with renal impairment: * Meet the following eGFR criteria during the screening period based on the MDRD equation: * Severe renal impairment: eGFR \<30 mL/min, but not requiring hemodialysis. * Moderate renal impairment (Part 2 only): eGFR ≥30 mL/min and \<60 mL/min. * Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included). * Stable concomitant drug regimen.
Exclusion criteria
* Renal transplant recipients. * Urinary incontinence without catheterization. * Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), evidence of any infection (including influenza) within the past 7 days prior to baseline, history of disseminated herpes simplex infection or recurrent or disseminated herpes zoster. * Subjects with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. * History of or current positive results for human immunodeficiency virus, Hepatitis B, Hepatitis C. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2) | 0 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. | Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2). |
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842 | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. | Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time. |
| Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. | Maximum observed plasma concentration for active metabolite, PF-06471658 (M1). |
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. | Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1). |
| Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. | Maximum observed plasma concentration for active metabolite, PF-07055087 (M2). |
| Maximum Observed Plasma Concentration (Cmax) for PF-04965842 | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose | Maximum observed plasma PF-04965842 concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Baseline, post-dose on Day 1, Day 2 and Day 4. | Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria. |
| Number of Participants With Clinically Significant Vital Sign Values | Day 1 (pre-dose) and Day 4 | Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator. |
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values | Baseline, post-dose on Day 1 and on Day 4 | Clinical significance of ECG data was assessed by the investigator. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Baseline up to Follow-Up (Day 36) | Adverse events (AEs): any untoward medical occurrence in a clinical investigation subject administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Causality to study treatment was determined by the investigator. |
Countries
Belgium, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normal Renal Function Participants were selected and categorized into the normal renal function group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula \>=90 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. | 8 |
| Moderate Renal Impairment Participants were selected and categorized into the moderate renal impairment group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula \>=30 and \<60 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. | 7 |
| Severe Renal Impairment Participants were selected and categorized into the severe renal impairment group with the estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) formula \<30 mL/min on Day -1 and not requiring dialysis. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. | 8 |
| Total | 23 |
Baseline characteristics
| Characteristic | Normal Renal Function | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|
| Age, Continuous | 59.8 Years STANDARD_DEVIATION 4.71 | 65.7 Years STANDARD_DEVIATION 8.34 | 61.0 Years STANDARD_DEVIATION 14.46 | 62.0 Years STANDARD_DEVIATION 9.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 7 Participants | 19 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 1 / 8 | 1 / 7 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842
Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842 | 4827 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 65 |
| Moderate Renal Impairment | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842 | 8828 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Severe Renal Impairment | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842 | 5855 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 73 |
Comparison: Test: the moderate renal impairment group; Reference: the normal renal function group90% CI: [117.09, 285.71]ANOVA
Comparison: Test: the severe renal impairment group; Reference: the normal renal function group90% CI: [68.32, 215.41]ANOVA
Primary
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1)
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1) | 872.6 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 44 |
| Moderate Renal Impairment | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1) | 1346 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| Severe Renal Impairment | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1) | 2505 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 45 |
Comparison: Test: the moderate renal impairment group; Reference: the normal renal function group90% CI: [105.11, 226.26]ANOVA
Comparison: Test: the severe renal impairment group; Reference: the normal renal function group90% CI: [196.72, 418.89]ANOVA
Primary
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2)
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2).
Time frame: 0 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2) | 1476 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| Moderate Renal Impairment | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2) | 3981 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| Severe Renal Impairment | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2) | 8433 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
Comparison: Test: the moderate renal impairment group; Reference: the normal renal function group90% CI: [196.61, 370.18]ANOVA
Comparison: Test: the severe renal impairment group; Reference: the normal renal function group90% CI: [447.27, 730.05]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax) for PF-04965842
Maximum observed plasma PF-04965842 concentration.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) for PF-04965842 | 1174 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) for PF-04965842 | 1626 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) for PF-04965842 | 1164 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 80 |
Comparison: Test: the moderate renal impairment group; Reference: the normal renal function group.90% CI: [93.74, 204.61]ANOVA
Comparison: Test: the severe renal impairment group; Reference: the normal renal function group90% CI: [57.3, 171.43]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1)
Maximum observed plasma concentration for active metabolite, PF-06471658 (M1).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1) | 193.7 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 54 |
| Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1) | 192.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 65 |
| Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1) | 325.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 81 |
Comparison: Test: the moderate renal impairment group; Reference: the normal renal function group90% CI: [59.8, 165.57]ANOVA
Comparison: Test: the severe renal impairment group; Reference: the normal renal function group90% CI: [97.2, 289.64]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)
Maximum observed plasma concentration for active metabolite, PF-07055087 (M2).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2) | 241.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2) | 331.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2) | 429.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Comparison: Test: the moderate renal impairment group; Reference: the normal renal function group90% CI: [106.82, 176.81]ANOVA
Comparison: Test: the severe renal impairment group; Reference: the normal renal function group90% CI: [135.91, 232.92]ANOVA
Secondary
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values
Clinical significance of ECG data was assessed by the investigator.
Time frame: Baseline, post-dose on Day 1 and on Day 4
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Normal Renal Function | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values | 0 Participants |
| Severe Renal Impairment | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Vital Sign Values
Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator.
Time frame: Day 1 (pre-dose) and Day 4
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Normal Renal Function | Number of Participants With Clinically Significant Vital Sign Values | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Clinically Significant Vital Sign Values | 0 Participants |
| Severe Renal Impairment | Number of Participants With Clinically Significant Vital Sign Values | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria.
Time frame: Baseline, post-dose on Day 1, Day 2 and Day 4.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Normal Renal Function | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 6 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 6 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 8 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Adverse events (AEs): any untoward medical occurrence in a clinical investigation subject administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Causality to study treatment was determined by the investigator.
Time frame: Baseline up to Follow-Up (Day 36)
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Renal Function | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All-causality | 1 Participants |
| Normal Renal Function | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All-causality | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related | 1 Participants |
| Severe Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All-causality | 0 Participants |
| Severe Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related | 0 Participants |
Post Hoc
Unbound Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf,u) of the Active Moiety
The unbound area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active moiety, calculated as the sum of unbound AUCinf for PF-04965842 and active metabolites, PF-06471658 (M1) and PF-07055087 (M2), adjusted for the relative potencies of the metabolites.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Unbound Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf,u) of the Active Moiety | 9955 nanomolar*hour (nM*hr) | Geometric Coefficient of Variation 40 |
| Moderate Renal Impairment | Unbound Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf,u) of the Active Moiety | 20920 nanomolar*hour (nM*hr) | Geometric Coefficient of Variation 28 |
| Severe Renal Impairment | Unbound Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf,u) of the Active Moiety | 28940 nanomolar*hour (nM*hr) | Geometric Coefficient of Variation 23 |
Comparison: Test: the moderate renal impairment group; Reference: the normal renal function group90% CI: [154.6, 285.8]ANOVA
Comparison: Test: the severe renal impairment group; Reference: the normal renal function group90% CI: [217.39, 388.69]ANOVA
Post Hoc
Unbound Maximum Observed Plasma Concentration (Cmax,u) of the Active Moiety
The unbound maximum observed plasma concentration for active moiety, calculated as the sum of unbound Cmax for PF-04965842 and active metabolites, PF-06471658 (M1) and PF-07055087 (M2), adjusted for the relative potencies of the metabolites.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Unbound Maximum Observed Plasma Concentration (Cmax,u) of the Active Moiety | 2099 nanomolar (nM) | Geometric Coefficient of Variation 38 |
| Moderate Renal Impairment | Unbound Maximum Observed Plasma Concentration (Cmax,u) of the Active Moiety | 2810 nanomolar (nM) | Geometric Coefficient of Variation 20 |
| Severe Renal Impairment | Unbound Maximum Observed Plasma Concentration (Cmax,u) of the Active Moiety | 2718 nanomolar (nM) | Geometric Coefficient of Variation 41 |
Comparison: Test: the moderate renal impairment group; Reference: the normal renal function group90% CI: [102.45, 174.92]ANOVA
Comparison: Test: the severe renal impairment group; Reference: the normal renal function group90% CI: [92.86, 180.57]ANOVA