Cough
Conditions
Keywords
Camlipixant, Healthy participants, Hepatic Impairment, Pharmacokinetic, Safety
Brief summary
The purpose of this study is to assess the effect of Hepatic impairment (HI) on the Pharmacokinetic (PK) profile and safety of Camlipixant.
Interventions
DRUGCamlipixant
Camlipixant was administered.
Sponsors
Bellus Health Inc. - a GSK company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This will be an open-label study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for all participants * Adult male or female participant, greater than or equals to (\>=) 18 years and less than or equals to (\<=) 75 years of age at the screening visit. * Male and female participants must follow protocol-specified contraception guidance. Guidance for Female Participants a. Female participants of childbearing potential must agree to one of the following methods of contraception: i. Hysteroscopic sterilization or bilateral tubal ligation at least 6 months prior to dosing. ii. Non-hormonal releasing intrauterine device (IUD) or hormonal contraceptives (e.g., oral, IUD, vaginal ring, transdermal patch, depot, implantable, etc.) for at least 3 months prior to dosing and with either a physical (e.g., condom, diaphragm, or other) or a chemical (e.g., spermicide) barrier method from the time of the screening visit. b. In addition, female participants of childbearing potential will be advised to keep the same birth control method for at least 30 days after dosing. c. Female participant must agree not to donate ova from dosing until at least 30 days after dosing. Guidance for male participants. a. Male participants who are not vasectomized for at least 4 months prior to dosing and who are sexually active with a female partner of childbearing potential must be willing to use one of the following acceptable contraceptive methods from dosing until 90 days after dosing. i. Simultaneous use of condom and hormonal contraceptive (e.g., oral, IUD, vaginal ring, patch, depot, implantable, etc.) or non-hormonal intrauterine device used for at least 3 months prior to dosing for the female partner. ii. Simultaneous use of condom and a diaphragm or cervical cap with spermicide for the female partner. b. No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to dosing. A male who has been vasectomized less than 4 months prior to dosing must follow the same restrictions as a non-vasectomized male. 1. Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a Woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of \<1 percent (%), during the study intervention period and for at least 14 days after the last dose of study intervention. The investigator should evaluate potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. 2. A WOCBP must have a negative highly sensitive pregnancy test urine or serum as required by local regulations) within specify timeframe before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. 3. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. * Participants must weigh at least 50 kilogram (kg) and have a Body mass index (BMI) \>= 18.0 and \<= 40.0 kilograms per square meter (kg/m\^2), at the screening visit. * Continuous non-smoker who has not used nicotine- and tobacco-containing products or light smoker (\<= 5 cigarettes/day or the equivalent) for the last 3 months prior to study screening. * Participant who understands the study procedures in the informed consent form (ICF) and is willing and able to comply with the protocol. Additional inclusion criteria for hepatic impaired participants. * Participants aside from HI, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, ECGs, and screening clinical laboratory profiles, as deemed by the Principal Investigator (PI) or designee, including the following: 1. Seated blood pressure is \>= 90/40 millimeters of mercury (mmHg) and \<= 160/100 mmHg at the screening visit. 2. Seated heart rate is \>= 40 beats per minute (bpm) and \<= 99 bpm at the screening visit. 3. Corrected value of the interval between the Q and T waves on the electrocardiogram tracing, corrected QT interval using Fridericia formula (QTcF) is \<= 480 milliseconds (msec) and has ECG findings considered normal or not clinically significant by the PI or designee at the screening visit. 4. Estimated creatinine clearance \>= 80 milliliters per minute (mL/min) at the screening visit. 5. Total bilirubin \<= 6 milligrams per deciliters (mg/dL). * Has a score on the Child-Pugh scale at the screening visit as follows: a. Severe HI: \>= 10 and \<= 15; or Moderate HI: \>= 7 and \<= 9; or Mild HI: \>= 5 and \<= 6. * Participant has stable HI as defined by a diagnosis of chronic (\>= 6 months), stable (no acute episodes of illness within 30 days prior to dosing due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology. Additional inclusion criteria for healthy control participants: * Medically healthy participants with no clinically significant medical history, physical examination, screening clinical laboratory profiles, vital signs and ECGs, as deemed by the PI or designee, including the following: 1. Seated blood pressure is \>= 90/40 mmHg and \<= 140/90 mmHg at the screening visit. 2. Seated heart rate is \>= 40 bpm and \<= 99 bpm at the screening visit. 3. QTcF interval is \<= 450 msec and has ECG findings considered normal or not clinically significant by the PI or designee at the screening visit. 4. QTc \<= 480 msec in participants with bundle branch block. * Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), direct bilirubin, indirect bilirubin, and total bilirubin within normal ranges at the screening visit and check-in. Only abnormal values up to 1.5 times upper limit of normal may be repeated once.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-inf]) of Camlipixant | 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 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: AUC(0-inf) of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Cmax of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to Day 5 | 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. |
| Part 2: Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to Day 5 | 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. |
| Part 1: Number of Participants With Clinically Significant Changes in Urinalysis | Up to Day 5 | 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. |
| Part 2: Number of Participants With Clinically Significant Changes in Urinalysis | Up to Day 5 | 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. |
| Part 1: Number of Participants With Clinically Significant Changes in Vital Signs | Up to Day 5 | 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. |
| Part 2: Number of Participants With Clinically Significant Changes in Vital Signs | Up to Day 5 | 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. |
| Part 1: Number of Participants With Clinically Significant Changes in 12 Lead Electrocardiogram (ECG) Findings | Up to Day 5 | 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. |
| Part 2: Number of Participants With Clinically Significant Changes in 12 Lead ECG Findings | Up to Day 5 | 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. |
| Part 1: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) | Up to 17 days | 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. |
| Part 2: Tmax of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 1: Terminal Elimination Half-life (T1/2) Following Administration of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: T1/2 Following Administration of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 1: Apparent Oral Clearance (CL/F) of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: CL/F of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 1: Apparent Oral Volume of Distribution (Vz/F) of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Vz/F of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Camlipixant | 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 | Blood samples were collected at indicated time points for PK analysis of camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Number of Participants With Any AE, SAE, and AESI | Up to 17 days | 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. |
| Part 1: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters | Up to Day 5 | 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. |
| Part 2: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters | Up to Day 5 | 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. |
Countries
United States
Participant flow
Recruitment details
This study consisted of 2 parts - Part 1 and Part 2. In Part 1, participants with moderate hepatic impairment (HI) and matched healthy participants were enrolled. Based on the pharmacokinetic (PK) and safety data from Part 1, only participants with severe HI and their matched healthy participants were enrolled in Part 2, while participants with mild HI were not enrolled.
Pre-assignment details
A total of 32 participants (16 in Part 1 and 16 in Part 2) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Moderate HI Participants Participants with moderate HI received a single dose of camlipixant 50 mg tablet orally on Day 1 in the fasted state. | 8 |
| Part 1: Matched Healthy Participants to Moderate HI Healthy participants (matched to participants with moderate HI) received a single dose of camlipixant 50 mg tablet orally on Day 1 in the fasted state. | 8 |
| Part 2: Severe HI Participants Participants with severe HI received a single dose of camlipixant 50 mg tablet orally on Day 1 in the fasted state. | 8 |
| Part 2: Matched Healthy Participants to Severe HI Healthy participants (matched to participants with severe HI) received a single dose of camlipixant 50 mg tablet orally on Day 1 in the fasted state. | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Part 1: Moderate HI Participants | Part 1: Matched Healthy Participants to Moderate HI | Part 2: Severe HI Participants | Part 2: Matched Healthy Participants to Severe HI | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.8 YEARS STANDARD_DEVIATION 9.92 | 56.8 YEARS STANDARD_DEVIATION 6.96 | 49.9 YEARS STANDARD_DEVIATION 9.95 | 51.6 YEARS STANDARD_DEVIATION 9.32 | 54.3 YEARS STANDARD_DEVIATION 9.42 |
| Race/Ethnicity, Customized White | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 32 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 20 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 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 2 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (non-quantifiable \[NQ\] values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-inf]) of Camlipixant | 5811 Hours*nanograms per milliliter | Geometric Coefficient of Variation 22.7 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-inf]) of Camlipixant | 4735 Hours*nanograms per milliliter | Geometric Coefficient of Variation 19 |
Primary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Maximum Observed Plasma Concentration (Cmax) of Camlipixant | 1317 Nanograms per milliliter | Geometric Coefficient of Variation 33.5 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Maximum Observed Plasma Concentration (Cmax) of Camlipixant | 960.0 Nanograms per milliliter | Geometric Coefficient of Variation 30.7 |
Primary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 2: AUC(0-inf) of Camlipixant | 7827 Hours*nanograms per milliliter | Geometric Coefficient of Variation 39.9 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: AUC(0-inf) of Camlipixant | 4662 Hours*nanograms per milliliter | Geometric Coefficient of Variation 46.9 |
Primary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Cmax of Camlipixant | 1228 Nanograms per milliliter | Geometric Coefficient of Variation 38.9 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Cmax of Camlipixant | 985.8 Nanograms per milliliter | Geometric Coefficient of Variation 29.8 |
Secondary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Apparent Oral Clearance (CL/F) of Camlipixant | 8.605 Liters per hour | Geometric Coefficient of Variation 22.7 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Apparent Oral Clearance (CL/F) of Camlipixant | 10.56 Liters per hour | Geometric Coefficient of Variation 19 |
Secondary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Apparent Oral Volume of Distribution (Vz/F) of Camlipixant | 75.74 Liters | Geometric Coefficient of Variation 36.3 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Apparent Oral Volume of Distribution (Vz/F) of Camlipixant | 88.49 Liters | Geometric Coefficient of Variation 20.4 |
Secondary
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.
Time frame: Up to 17 days
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) | Any AE | 0 Participants |
| Part 1: Moderate HI Participants | Part 1: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) | Any SAE | 0 Participants |
| Part 1: Moderate HI Participants | Part 1: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) | Any AESI | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) | Any AE | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) | Any SAE | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) | Any AESI | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Number of Participants With Clinically Significant Changes in 12 Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Number of Participants With Clinically Significant Changes in 12 Lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Number of Participants With Clinically Significant Changes in Hematology Parameters | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Number of Participants With Clinically Significant Changes in Hematology Parameters | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Number of Participants With Clinically Significant Changes in Urinalysis | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Number of Participants With Clinically Significant Changes in Urinalysis | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Terminal Elimination Half-life (T1/2) Following Administration of Camlipixant | 6.101 Hours | Geometric Coefficient of Variation 46.8 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Terminal Elimination Half-life (T1/2) Following Administration of Camlipixant | 5.809 Hours | Geometric Coefficient of Variation 14.4 |
Secondary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Camlipixant | 0.750 Hours |
| Part 1: Matched Healthy Participants to Moderate HI | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Camlipixant | 1.000 Hours |
Secondary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 2: CL/F of Camlipixant | 6.388 Liters per hour | Geometric Coefficient of Variation 39.9 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: CL/F of Camlipixant | 10.73 Liters per hour | Geometric Coefficient of Variation 46.9 |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Number of Participants With Any AE, SAE, and AESI | Any AE | 2 Participants |
| Part 1: Moderate HI Participants | Part 2: Number of Participants With Any AE, SAE, and AESI | Any SAE | 0 Participants |
| Part 1: Moderate HI Participants | Part 2: Number of Participants With Any AE, SAE, and AESI | Any AESI | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Number of Participants With Any AE, SAE, and AESI | Any AE | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Number of Participants With Any AE, SAE, and AESI | Any SAE | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Number of Participants With Any AE, SAE, and AESI | Any AESI | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Number of Participants With Clinically Significant Changes in 12 Lead ECG Findings | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Number of Participants With Clinically Significant Changes in 12 Lead ECG Findings | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Number of Participants With Clinically Significant Changes in Hematology Parameters | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Number of Participants With Clinically Significant Changes in Hematology Parameters | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Number of Participants With Clinically Significant Changes in Urinalysis | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Number of Participants With Clinically Significant Changes in Urinalysis | 0 Participants |
Secondary
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
Population: The analysis was performed on the Safety Analysis Set that included all participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 2: T1/2 Following Administration of Camlipixant | 6.626 Hours | Geometric Coefficient of Variation 17.1 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: T1/2 Following Administration of Camlipixant | 7.855 Hours | Geometric Coefficient of Variation 56.3 |
Secondary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Tmax of Camlipixant | 0.750 Hours |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Tmax of Camlipixant | 0.875 Hours |
Secondary
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
Population: The analysis was performed on the PK Analysis Set that included all participants who received study intervention and who had at least 1 non-missing PK assessment (NQ values were considered as non-missing values).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Moderate HI Participants | Part 2: Vz/F of Camlipixant | 61.06 Liters | Geometric Coefficient of Variation 32.5 |
| Part 1: Matched Healthy Participants to Moderate HI | Part 2: Vz/F of Camlipixant | 121.6 Liters | Geometric Coefficient of Variation 42.5 |