Renal Impairment Study of PF-06700841
- Registration Number
- NCT04260464
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- 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
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-06700841 Normal Renal Function PF-06700841 This arm includes participants with normal renal function who will receive a single oral dose of 30 mg PF-06700841 on Day 1 PF-06700841 Moderate Renal Impairment PF-06700841 This arm includes participants with moderate renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1 PF-06700841 Severe Renal Impairment PF-06700841 This arm includes participants with severe renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1 PF-06700841 Mild Renal Impairment PF-06700841 This arm includes participants with mild renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1
- Primary Outcome Measures
Name Time Method 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.
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.
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.
- Secondary Outcome Measures
Name Time Method 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.
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 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.
Trial Locations
- Locations (3)
Prism Research LLC dba Nucleus Network
🇺🇸Saint Paul, Minnesota, United States
Investigational Drug Services (IDS) University of Miami Hospitals and Clinics, Research Pharmacy
🇺🇸Miami, Florida, United States
University of Miami Division of Clinical Pharmacology
🇺🇸Miami, Florida, United States