Healthy Volunteer, Renal Impairment
Conditions
Keywords
Pharmacokinetics
Brief summary
The purpose of this study is to characterize the effect of kidney impairment on the blood concentrations of PF-06700841 and its major metabolite. Findings from this study will be used to develop dosing recommendations so that the dose and/or dosing interval may be adjusted appropriately in the presence of kidney disease.
Detailed description
This is a Phase 1 non-randomized, open-label, parallel cohort, multi-site study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-06700841 after a single oral dose of 30 mg. 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 approximately 16 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 with approximately 8 subjects each with moderate and mild renal impairment. The total duration of participation from Screening visit to Day 4 will be a maximum of 32 days and from Screening visit to Follow-up/Contact Visit will a maximum of 67 days.
Interventions
DRUGPF-06700841
A single dose of 30 mg PF-06700841 will be administered on Day 1
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Masking description
No Masking
Intervention model description
Single group
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female participants who are between the ages of 18 and 75 years, inclusive, at the Screening visit. * Body mass index (BMI) of ≥17.5 to ≤40 kg/m2; and a total body weight \>50 kg. * Normal, Severe, Moderate and Mild renal function at 2 Screening visits. * Stable drug regimen
Exclusion criteria
* Renal transplant recipients. * Urinary incontinence without catheterization. * Subjects with clinically significant infections within the past 6 months prior to first dose of study drug, evidence of active or chronic infection requiring oral treatment within 4 weeks prior to first dose * Known history of pulmonary embolism or recurrent deep vein thrombosis * Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCinf of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose | AUCinf was area under the concentration-time curve from time 0 to infinity, which was calculated for PF-06802530 (M1), a major metabolite of PF-06700841 from the concentration-time data. |
| Maximum Observed Plasma Concentration (Cmax) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose | Cmax is the maximum observed plasma concentration of PF-06700841 within 72 hours post dose, which was observed directly from the plasma concentration-time data. |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose | AUCinf was area under the concentration-time curve from time 0 to infinity, which was calculated for PF-06700841 from the concentration-time data. |
| Cmax of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose | Cmax is the maximum observed plasma concentration of PF-06802530 (M1), a major metabolite of PF-06700841 within 72 hours post dose, which was observed directly from the plasma concentration-time data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From screening (Day-28 to Day -2) to up to 35 days after the study treatment (for a period of up to 63 days) | Any events occurring following start of treatment or increasing in severity after the start of the treatment were counted as treatment emergent. An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect. Severe adverse events is an event that prevents normal everyday activities which is a category utilized for rating the intensity of an event. |
| Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Baseline (Day -1) and Day 4 | The hematology, clinical chemistry and urinalysis abnormalities were summarized in accordance with the sponsor reporting standards without regard to baseline abnormality. Baseline is defined as the last planned predose measurement taken on Day -1. |
| Number of Participants With Post-baseline Vital Sign Abnormalities | Baseline (Day 1) and Day 4 | Vital Signs were assessed against the criteria specified in the sponsor reporting standards for potential clinical concerns. Vital sign abnormalities criteria included: 1) Systolic blood pressure (BP) in millimeters of mercury (mmHg): \<90 mmHg with increase or decrease from baseline of ≥30 mmHg with high and low post baseline values; 2) Diastolic blood pressure (BP) (mmHg): \<50 mmHg with increase or decrease from baseline of ≥20 mmHg with high and low post baseline values; 3) Supine pulse rate in beats per minutes (bpm): \>120 or \<40 bpm. Categories with at least 1 participant having vital sign abnormality in any of the reporting arms, were reported in this outcome measure. Baseline is defined as the last planned predose measurement taken on Day 1. |
| Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | 0 hr pre-dose and 1-, 3-, and 6-hours post-dose on Day 1; Day 4 | ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): \> 450, \>480, \>500, increase from baseline \>30, increase from baseline \>60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): \>450, \>480, \>500, increase from baseline \>30, increase from baseline \>60. Categories with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure. Baseline is defined as the last planned predose measurement taken on Day 1. |
Countries
United States
Participant flow
Recruitment details
Healthy adult participants with normal renal function and adult participants with renal impairment were enrolled in this study.
Pre-assignment details
A total of 30 participants who met the eligibility criteria were assigned and treated.
Participants by arm
| Arm | Count |
|---|---|
| Severe Renal Impairment Participants with eGFR \<30 ml/min and not requiring dialysis were categorized into the severe renal impairment arm. Participants received a single dose of PF-06700841 30 mg tablets (2 tablets as 1 x 5 mg and 1 x 25 mg) orally. | 8 |
| Normal Renal Function Participants with eGFR ≥90 mL/min were categorized into the normal renal function arm. Participants received a single dose of PF-06700841 30 mg tablets (2 tablets as 1 × 5 mg and 1 × 25 mg) orally. | 7 |
| Moderate Renal Impairment Participants with eGFR ≥30 to \<60 mL/min were categorized into the moderate renal impairment arm. Participants received a single dose of PF-06700841 30 mg tablets (2 tablets as 1 × 5 mg and 1 × 25 mg) orally. | 7 |
| Mild Renal Impairment Participants with eGFR ≥60 to \<89 mL/min were categorized into the mild renal impairment arm. Participants received a single dose of PF-06700841 30 mg tablets (2 tablets as 1 × 5 mg and 1 × 25 mg) orally. | 8 |
| Total | 30 |
Baseline characteristics
| Characteristic | Severe Renal Impairment | Normal Renal Function | Moderate Renal Impairment | Mild Renal Impairment | Total |
|---|---|---|---|---|---|
| Age, Continuous Mean (SD) | 65.9 Years STANDARD_DEVIATION 7.57 | 62.4 Years STANDARD_DEVIATION 5.38 | 68.4 Years STANDARD_DEVIATION 4.24 | 61.5 Years STANDARD_DEVIATION 6.16 | 64.5 Years STANDARD_DEVIATION 6.36 |
| Age, Customized 45-64 Years | 3 Participants | 6 Participants | 1 Participants | 6 Participants | 16 Participants |
| Age, Customized >=65 Years | 5 Participants | 1 Participants | 6 Participants | 2 Participants | 14 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 14 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 5 Participants | 6 Participants | 8 Participants | 27 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 5 Participants | 4 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 2 / 8 | 0 / 7 | 1 / 7 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 8 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function
AUCinf was area under the concentration-time curve from time 0 to infinity, which was calculated for PF-06700841 from the concentration-time data.
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose
Population: The PK parameter analysis population is defined as all participants assigned to investigational product and treated who have at least 1 of the PK parameters of primary interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment | Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 2013 ng*hr/mL | Geometric Coefficient of Variation 57 |
| Normal Renal Function | Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 1796 ng*hr/mL | Geometric Coefficient of Variation 77 |
| Moderate Renal Impairment | Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 2652 ng*hr/mL | Geometric Coefficient of Variation 75 |
| Mild Renal Impairment | Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 1274 ng*hr/mL | Geometric Coefficient of Variation 199 |
Comparison: ANOVA was used to compare the natural log transformed AUCinf for PF-06700841 between normal renal function group (Reference) and the severe impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.95% CI: [60.85, 206.45]
Comparison: ANOVA was used to compare the natural log transformed AUCinf for PF-06700841 between normal renal function group (Reference) and the mild impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.90% CI: [27.6, 182.49]
Comparison: ANOVA was used to compare the natural log transformed AUCinf for PF-06700841 between normal renal function group (Reference) and the moderate impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.90% CI: [75.17, 290.21]
Primary
AUCinf of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function
AUCinf was area under the concentration-time curve from time 0 to infinity, which was calculated for PF-06802530 (M1), a major metabolite of PF-06700841 from the concentration-time data.
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose
Population: The PK parameter analysis population is defined as all participants assigned to investigational product and treated who have at least 1 of the PK parameters of primary interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment | AUCinf of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 7756 ng*hr/mL | Geometric Coefficient of Variation 41 |
| Normal Renal Function | AUCinf of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 1739 ng*hr/mL | Geometric Coefficient of Variation 24 |
| Moderate Renal Impairment | AUCinf of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 3984 ng*hr/mL | Geometric Coefficient of Variation 15 |
| Mild Renal Impairment | AUCinf of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 2515 ng*hr/mL | Geometric Coefficient of Variation 32 |
Comparison: ANOVA was used to compare the natural log transformed AUCinf for M1 between normal renal function group (Reference) and the severe impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.95% CI: [326.55, 609.13]
Comparison: ANOVA was used to compare the natural log transformed AUCinf for M1 between normal renal function group (Reference) and the mild impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.90% CI: [112.76, 185.5]
Comparison: ANOVA was used to compare the natural log transformed AUCinf for M1 between normal renal function group (Reference) and the moderate impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.90% CI: [189.97, 276.35]
Primary
Cmax of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function
Cmax is the maximum observed plasma concentration of PF-06802530 (M1), a major metabolite of PF-06700841 within 72 hours post dose, which was observed directly from the plasma concentration-time data.
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose
Population: The PK concentration population is defined as all participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment | Cmax of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 250.4 ng/mL | Geometric Coefficient of Variation 26 |
| Normal Renal Function | Cmax of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 141.0 ng/mL | Geometric Coefficient of Variation 32 |
| Moderate Renal Impairment | Cmax of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 172.1 ng/mL | Geometric Coefficient of Variation 46 |
| Mild Renal Impairment | Cmax of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 187.1 ng/mL | Geometric Coefficient of Variation 43 |
Comparison: ANOVA was used to compare the natural log transformed Cmax for M1 between normal renal function group (Reference) and the severe impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.95% CI: [135.82, 232.04]
Comparison: ANOVA was used to compare the natural log transformed Cmax for M1 between normal renal function group (Reference) and the mild impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.90% CI: [95.08, 185.17]
Comparison: ANOVA was used to compare the natural log transformed Cmax for M1 between normal renal function group (Reference) and the moderate impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs were obtained from the model.90% CI: [84.47, 176.3]
Primary
Maximum Observed Plasma Concentration (Cmax) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function
Cmax is the maximum observed plasma concentration of PF-06700841 within 72 hours post dose, which was observed directly from the plasma concentration-time data.
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose
Population: The PK concentration population is defined as all participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 303.2 ng/mL | Geometric Coefficient of Variation 34 |
| Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 275.2 ng/mL | Geometric Coefficient of Variation 27 |
| Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 341.8 ng/mL | Geometric Coefficient of Variation 17 |
| Mild Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function | 260.3 ng/mL | Geometric Coefficient of Variation 89 |
Comparison: Analysis of variance (ANOVA) was used to compare the natural log transformed Cmax for PF-06700841 between the normal renal function group (Reference) and the severe impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence intervals (CIs) were obtained from the model.95% CI: [83.76, 144.86]
Comparison: ANOVA was used to compare the natural log transformed Cmax for PF-06700841 between the normal renal function group (Reference) and the mild impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence intervals (CIs) were obtained from the model.90% CI: [55.84, 160.19]
Comparison: ANOVA was used to compare the natural log transformed Cmax for PF-06700841 between the normal renal function group (Reference) and the moderate impaired renal function group (Test). Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% confidence intervals (CIs) were obtained from the model.90% CI: [100.24, 153.89]
Secondary
Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
The hematology, clinical chemistry and urinalysis abnormalities were summarized in accordance with the sponsor reporting standards without regard to baseline abnormality. Baseline is defined as the last planned predose measurement taken on Day -1.
Time frame: Baseline (Day -1) and Day 4
Population: The analysis population included all participants assigned to investigational product and who take at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Creatinine (mg/dL) >1.3✕ULN | 8 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Blood Urea Nitrogen (mg/dL) >1.3✕ULN | 8 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Lymphocytes/Leukocytes (%) <0.8✕LLN | 1 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Leukocyte Esterase ≥1 | 1 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Eosinophils/Leukocytes (%) >1.2✕ULN | 2 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Lymphocytes/Leukocytes (%) >1.2✕ULN | 0 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Protein ≥1 | 2 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Glucose ≥1 | 2 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Erythrocytes (10^6/mm^3) <0.8✕LLN | 1 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Hemoglobin (HGB) (g/dL) <0.8✕lower limit of normal (LLN) | 2 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Glucose (mg/dL) >1.5✕ULN | 1 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Bicarbonate (mEq/L) <0.9✕LLN | 1 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology- Erythromycin (Ery.) Mean Corpuscular HGB (pg/cell) >1.1✕upper limit of normal (ULN) | 1 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Hemoglobin ≥1 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Potassium (mEq/L) >1.1✕ULN | 0 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Urate (mg/dL) > 1.2✕ULN | 5 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Ery. Mean Corpuscular HGB Concentration (g/dL) <0.9✕LLN | 0 Participants |
| Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Hematocrit (%) <0.8✕LLN | 1 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Erythrocytes (10^6/mm^3) <0.8✕LLN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Hemoglobin (HGB) (g/dL) <0.8✕lower limit of normal (LLN) | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Hematocrit (%) <0.8✕LLN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology- Erythromycin (Ery.) Mean Corpuscular HGB (pg/cell) >1.1✕upper limit of normal (ULN) | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Ery. Mean Corpuscular HGB Concentration (g/dL) <0.9✕LLN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Lymphocytes/Leukocytes (%) <0.8✕LLN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Lymphocytes/Leukocytes (%) >1.2✕ULN | 1 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Eosinophils/Leukocytes (%) >1.2✕ULN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Blood Urea Nitrogen (mg/dL) >1.3✕ULN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Creatinine (mg/dL) >1.3✕ULN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Urate (mg/dL) > 1.2✕ULN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Potassium (mEq/L) >1.1✕ULN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Bicarbonate (mEq/L) <0.9✕LLN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Glucose (mg/dL) >1.5✕ULN | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Glucose ≥1 | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Protein ≥1 | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Hemoglobin ≥1 | 0 Participants |
| Normal Renal Function | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Leukocyte Esterase ≥1 | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Ery. Mean Corpuscular HGB Concentration (g/dL) <0.9✕LLN | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Creatinine (mg/dL) >1.3✕ULN | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Urate (mg/dL) > 1.2✕ULN | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology- Erythromycin (Ery.) Mean Corpuscular HGB (pg/cell) >1.1✕upper limit of normal (ULN) | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Leukocyte Esterase ≥1 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Potassium (mEq/L) >1.1✕ULN | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Hemoglobin ≥1 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Bicarbonate (mEq/L) <0.9✕LLN | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Erythrocytes (10^6/mm^3) <0.8✕LLN | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Glucose (mg/dL) >1.5✕ULN | 4 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Hemoglobin (HGB) (g/dL) <0.8✕lower limit of normal (LLN) | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Glucose ≥1 | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Hematocrit (%) <0.8✕LLN | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Lymphocytes/Leukocytes (%) >1.2✕ULN | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Lymphocytes/Leukocytes (%) <0.8✕LLN | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Eosinophils/Leukocytes (%) >1.2✕ULN | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Protein ≥1 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Blood Urea Nitrogen (mg/dL) >1.3✕ULN | 2 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Lymphocytes/Leukocytes (%) >1.2✕ULN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Protein ≥1 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Glucose (mg/dL) >1.5✕ULN | 2 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Creatinine (mg/dL) >1.3✕ULN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology- Erythromycin (Ery.) Mean Corpuscular HGB (pg/cell) >1.1✕upper limit of normal (ULN) | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Hemoglobin (HGB) (g/dL) <0.8✕lower limit of normal (LLN) | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Hematocrit (%) <0.8✕LLN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Urate (mg/dL) > 1.2✕ULN | 1 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Ery. Mean Corpuscular HGB Concentration (g/dL) <0.9✕LLN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Leukocyte Esterase ≥1 | 2 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Glucose ≥1 | 1 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Potassium (mEq/L) >1.1✕ULN | 1 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Erythrocytes (10^6/mm^3) <0.8✕LLN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Lymphocytes/Leukocytes (%) <0.8✕LLN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Blood Urea Nitrogen (mg/dL) >1.3✕ULN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Clinical chemistry-Bicarbonate (mEq/L) <0.9✕LLN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Hematology-Eosinophils/Leukocytes (%) >1.2✕ULN | 0 Participants |
| Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Urinalysis-Urine Hemoglobin ≥1 | 1 Participants |
Secondary
Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities
ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): \> 450, \>480, \>500, increase from baseline \>30, increase from baseline \>60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): \>450, \>480, \>500, increase from baseline \>30, increase from baseline \>60. Categories with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure. Baseline is defined as the last planned predose measurement taken on Day 1.
Time frame: 0 hr pre-dose and 1-, 3-, and 6-hours post-dose on Day 1; Day 4
Population: All assigned to investigational product and who take at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Severe Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcF interval, single beat (msec): 450 < Value ≤ 480 | 2 Participants |
| Severe Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcF interval, single beat (msec): 30 ≤ Change ≤ 60 | 0 Participants |
| Severe Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcB interval, single beat (msec): 450 < Value ≤ 480 | 2 Participants |
| Severe Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcB interval, single beat (msec): 30 ≤ Change ≤ 60 | 0 Participants |
| Normal Renal Function | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcB interval, single beat (msec): 30 ≤ Change ≤ 60 | 0 Participants |
| Normal Renal Function | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcB interval, single beat (msec): 450 < Value ≤ 480 | 0 Participants |
| Normal Renal Function | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcF interval, single beat (msec): 30 ≤ Change ≤ 60 | 0 Participants |
| Normal Renal Function | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcF interval, single beat (msec): 450 < Value ≤ 480 | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcB interval, single beat (msec): 450 < Value ≤ 480 | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcB interval, single beat (msec): 30 ≤ Change ≤ 60 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcF interval, single beat (msec): 30 ≤ Change ≤ 60 | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcF interval, single beat (msec): 450 < Value ≤ 480 | 1 Participants |
| Mild Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcF interval, single beat (msec): 30 ≤ Change ≤ 60 | 2 Participants |
| Mild Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcF interval, single beat (msec): 450 < Value ≤ 480 | 0 Participants |
| Mild Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcB interval, single beat (msec): 30 ≤ Change ≤ 60 | 3 Participants |
| Mild Renal Impairment | Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities | QTcB interval, single beat (msec): 450 < Value ≤ 480 | 3 Participants |
Secondary
Number of Participants With Post-baseline Vital Sign Abnormalities
Vital Signs were assessed against the criteria specified in the sponsor reporting standards for potential clinical concerns. Vital sign abnormalities criteria included: 1) Systolic blood pressure (BP) in millimeters of mercury (mmHg): \<90 mmHg with increase or decrease from baseline of ≥30 mmHg with high and low post baseline values; 2) Diastolic blood pressure (BP) (mmHg): \<50 mmHg with increase or decrease from baseline of ≥20 mmHg with high and low post baseline values; 3) Supine pulse rate in beats per minutes (bpm): \>120 or \<40 bpm. Categories with at least 1 participant having vital sign abnormality in any of the reporting arms, were reported in this outcome measure. Baseline is defined as the last planned predose measurement taken on Day 1.
Time frame: Baseline (Day 1) and Day 4
Population: The analysis population included all assigned to investigational product and who take at least 1 dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Severe Renal Impairment | Number of Participants With Post-baseline Vital Sign Abnormalities | 0 Participants |
| Normal Renal Function | Number of Participants With Post-baseline Vital Sign Abnormalities | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Post-baseline Vital Sign Abnormalities | 0 Participants |
| Mild Renal Impairment | Number of Participants With Post-baseline Vital Sign Abnormalities | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any events occurring following start of treatment or increasing in severity after the start of the treatment were counted as treatment emergent. An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect. Severe adverse events is an event that prevents normal everyday activities which is a category utilized for rating the intensity of an event.
Time frame: From screening (Day-28 to Day -2) to up to 35 days after the study treatment (for a period of up to 63 days)
Population: The analysis population included all assigned to investigational product and who take at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Severe Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with severe adverse events | 0 Participants |
| Severe Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with adverse events | 2 Participants |
| Severe Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with serious adverse events | 0 Participants |
| Severe Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants discontinued from study due to adverse events | 0 Participants |
| Normal Renal Function | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with serious adverse events | 0 Participants |
| Normal Renal Function | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants discontinued from study due to adverse events | 0 Participants |
| Normal Renal Function | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with severe adverse events | 0 Participants |
| Normal Renal Function | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with adverse events | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with adverse events | 1 Participants |
| Moderate Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants discontinued from study due to adverse events | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with serious adverse events | 0 Participants |
| Moderate Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with severe adverse events | 0 Participants |
| Mild Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with serious adverse events | 0 Participants |
| Mild Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with severe adverse events | 0 Participants |
| Mild Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants with adverse events | 3 Participants |
| Mild Renal Impairment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Participants discontinued from study due to adverse events | 0 Participants |