The purpose of this study is to assess the effect of Hepatic impairment (HI) on the Pharmacokinetic (PK) profile and safety of Camlipixant.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Camlipixant was administered.
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
Orlando, Florida, United States
GSK Investigational Site
San Antonio, Texas, United States
Part 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-inf]) of Camlipixant
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 2: AUC(0-inf) of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 1: Maximum Observed Plasma Concentration (Cmax) of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 2: Cmax of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 1: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are 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 or significant disability/incapacity; is a congenital anomaly/birth defect in a participant's offspring; abnormal pregnancy outcomes; is a suspected transmission of any infectious agent via an authorized medicinal product; or other situations as per medical and scientific judgement of the Investigator. AESIs are AEs of scientific interest specific to the drug class. AESIs for this study include the following but not limited to taste disturbance (dysgeusia, hypogeusia, ageusia), oral paresthesia and oral hypoesthesia. Number of participants with any AE, SAE, or AESI were reported.
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Time frame: Up to 17 days
Part 2: Number of Participants With Any AE, SAE, and AESI
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are 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 or significant disability/incapacity; is a congenital anomaly/birth defect in a participant's offspring; abnormal pregnancy outcomes; is a suspected transmission of any infectious agent via an authorized medicinal product; or other situations as per medical and scientific judgement of the Investigator. AESIs are AEs of scientific interest specific to the drug class. AESIs for this study include the following but not limited to taste disturbance (dysgeusia, hypogeusia, ageusia), oral paresthesia and oral hypoesthesia. Number of participants with any AE, SAE, or AESI were reported.
Time frame: Up to 17 days
Part 1: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters
Blood samples were collected to analyze clinical chemical parameters: blood urea nitrogen (BUN)/urea, potassium, creatinine, sodium, calcium, glucose \[fasting/non-fasting\], creatine phosphokinase (CPK), serum albumin concentration, serum alpha-1-glycoprotein concentration, aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase, total bilirubin, direct bilirubin, indirect bilirubin and total protein. Number of participants with clinically significant changes in clinical chemistry parameters has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 2: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters
Blood samples were collected to analyze clinical chemical parameters: BUN/urea, potassium, creatinine, sodium, calcium, glucose \[fasting/non-fasting\], CPK, serum albumin concentration, serum alpha-1-glycoprotein concentration, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, direct bilirubin, indirect bilirubin and total protein. Number of participants with clinically significant changes in clinical chemistry parameters has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 1: Number of Participants With Clinically Significant Changes in Hematology Parameters
Blood samples were collected to analyze hematology parameters: platelet count, red blood cell (RBC) count, RBC indices (mean corpuscular volume \[MCV\], mean corpuscular hemoglobin \[MCH\], percent reticulocytes), white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophil, basophils), hemoglobin, and hematocrit. Number of participants with clinically significant changes in hematology parameters has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 2: Number of Participants With Clinically Significant Changes in Hematology Parameters
Blood samples were collected to analyze hematology parameters: platelet count, RBC count, RBC indices (MCV, MCH, percent reticulocytes), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophil, basophils), hemoglobin, and hematocrit. Number of participants with clinically significant changes in hematology parameters has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 1: Number of Participants With Clinically Significant Changes in Urinalysis
Urine samples were collected to analyze urinalysis parameters: specific gravity; and potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase which were analyzed by dipstick. Number of participants with clinically significant changes in urinalysis parameters has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 2: Number of Participants With Clinically Significant Changes in Urinalysis
Urine samples were collected to analyze urinalysis parameters: specific gravity; and pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase which were analyzed by dipstick. Number of participants with clinically significant changes in urinalysis parameters has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 1: Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs including systolic and diastolic blood pressure, pulse rate, respiratory rate, and temperature were measured. Blood pressure and pulse rate measurements were performed with participants in a seated position for at least 5 minutes, except when they were supine or semi-reclined because of study procedures and/or AEs (such as nausea, dizziness). Number of participants with abnormal clinically significant changes in vital signs has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 2: Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs including systolic and diastolic blood pressure, pulse rate, respiratory rate, and temperature were measured. Blood pressure and pulse rate measurements were performed with participants in a seated position for at least 5 minutes, except when they were supine or semi-reclined because of study procedures and/or AEs (such as nausea, dizziness). Number of participants with abnormal clinically significant changes in vital signs has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 1: Number of Participants With Clinically Significant Changes in 12 Lead Electrocardiogram (ECG) Findings
ECG values included measurements of heart rate, PR interval, QRS interval, uncorrected QT interval, and corrected QT interval using Fridericia formula (QTcF). 12-lead ECG was recorded with the participant in a supine position for at least 5 minutes. Number of participants with clinically significant 12-lead ECG findings has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 2: Number of Participants With Clinically Significant Changes in 12 Lead ECG Findings
ECG values included measurements of heart rate, PR interval, QRS interval, uncorrected QT interval, and QTcF. 12-lead ECG was recorded with the participant in a supine position for at least 5 minutes. Number of participants with clinically significant 12-lead ECG findings has been reported. Clinical significance was determined by the Investigator.
Time frame: Up to Day 5
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 2: Tmax of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 1: Terminal Elimination Half-life (T1/2) Following Administration of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 2: T1/2 Following Administration of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 1: Apparent Oral Clearance (CL/F) of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 2: CL/F of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 1: Apparent Oral Volume of Distribution (Vz/F) of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose
Part 2: Vz/F of Camlipixant
Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose