Moderate Hepatic Impairment, Normal Hepatic Function
Conditions
Keywords
Hepatic Impairment, Rivipansel
Brief summary
The purpose of this study is to determine the effect of hepatic impairment on rivipansel PK and safety.
Interventions
DRUGRivipansel
A single dose of IV Rivipansel over 20 minutes
Sponsors
GlycoMimetics Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Female subjects of non-childbearing potential or male subjects * Body Mass Index (BMI) of 17.5 to 40.0 kg/m2 * Normal Hepatic function for the healthy subjects * Stable Hepatic Impairment for the subjects with moderate hepatic impairment
Exclusion criteria
* Treatment with an investigational drug within 30 days of the dose of study medication * Pregnant females, breastfeeding female subjects and male subjects with partners currently pregnant * Use of herbal supplements in the 28 days prior to the dose of study medication * Blood donation (excluding plasma donation) of approximately 1 pint or more within 56 days prior to study medication * A positive urine drug screen for illicit drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Clearance From Plasma (CL) of Rivipansel | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | CL of rivipansel was calculated as dose/AUCinf, where AUCinf referred to the area under the plasma concentration-time profile from time 0 extrapolated to the infinite time. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Day 1 to follow-up visit (28-31 days after administration of study medication on Day 1) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between administration of study medication and up to follow-up visit (28-31 days after administration) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs. |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | Day 5 | Maximum absolute values and increases from baseline were summarized for PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization), QRS duration (time from Q wave to the end of S wave, corresponding to ventricle depolarization), and QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with ECG findings meeting the following criteria is presented: (1) PR interval \>=300 msec; (2) QRS duration \>=200 msec; (3) QTcF interval: 450 to \<480 msec; (4) QTcF interval: 480 to \<500 msec; (5) QTcF interval \>=500 msec; (6) PR interval percent increase from baseline \>=25/50 percent; (7) QRS duration percent increase from baseline \>=50 percent; (8) QTcF interval increase from baseline: 30 to \<60 msec; (9) QTcF interval increase from baseline \>=60 msec. |
| Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | Day 1 to Day 5 | Absolute values and changes from baseline (increase and decrease) were summarized for supine diastolic blood pressure (DBP), supine systolic blood pressure (SBP), and supine pulse rate. Number of participants with vital signs findings meeting the following criteria is presented: (1) supine DBP \<50 millimeters of mercury (mm Hg); (2) supine DBP \>90 mm Hg; (3) supine SBP \<90 mm Hg; (4) supine SBP \>140 mm Hg (for normal hepatic function group); (5) supine SBP \>160 mm Hg (for moderate hepatic impairment group); (6) supine pulse rate \< 40 beats per minute (bpm); (7) supine pulse rate \>120 bpm; (8) supine DBP increase from baseline \>=20 mm Hg; (9) supine SBP increase from baseline \>=30 mmHg; (10) supine DBP decrease from baseline \>=20 mm Hg; (11) supine SBP decrease from baseline \>=30 mm Hg. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Day 5 | Laboratory tests included: hematology (hemoglobin, hematocrit, red and white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, prothrombin time/international normalized ratio), chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate and alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (pH, qualitative glucose, protein, and blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, and microscopy), and other tests (follicle stimulating hormone, urine drug test and serologic tests on human immunodeficiency virus-1 antibody, Hepatitis B surface antigen and hepatitis C antibody). Abnormality was determined by the investigator using widely accepted criteria in clinical practice. |
| Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Rivipansel | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | AUCinf was calculated as AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log linear regression analysis, kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Number of Participants With Post-baseline Clinically Significant Findings in Physical Examinations | Day 5 | A full physical examination was performed for each participant, and it included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes and gastrointestinal, musculoskeletal, and neurological systems. Clinical significance of laboratory findings was determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Rivipansel | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of rivipansel was determined using a linear/log trapezoidal method. |
| Maximum Observed Concentration (Cmax) of Rivipansel | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | — |
| Terminal Half-Life of Rivipansel | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | Terminal half-life of rivipansel was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. |
| Volume of Distribution at Steady State (Vss) of Rivipansel | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 | Vss of rivipansel was calculated as CL\*MRT, where MRT was the mean residence time and CL was the clearance from plasma. |
Other
| Measure | Time frame |
|---|---|
| Time for Maximum Observed Concentration (Tmax) of Rivipansel | Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Moderate Hepatic Impairment Group A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with moderate hepatic impairment. | 8 |
| Normal Hepatic Function Group A single dose of rivipansel 840 mg was administered intravenously (IV) to a group of participants with normal hepatic function. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Normal Hepatic Function Group | Total | Moderate Hepatic Impairment Group |
|---|---|---|---|
| Age, Continuous | 58.75 years STANDARD_DEVIATION 4.43 | 58.38 years STANDARD_DEVIATION 4.03 | 58.00 years STANDARD_DEVIATION 3.85 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 1 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Rivipansel
AUCinf was calculated as AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log linear regression analysis, kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1
Population: The pharmacokinetic (PK) parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Rivipansel | 599.7 hour*microgram/milliliter (hr*mcg/mL) | Geometric Coefficient of Variation 25 |
| Normal Hepatic Function Group | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Rivipansel | 770.0 hour*microgram/milliliter (hr*mcg/mL) | Geometric Coefficient of Variation 14 |
90% CI: [0.6514, 0.9313]
Primary
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria
Maximum absolute values and increases from baseline were summarized for PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization), QRS duration (time from Q wave to the end of S wave, corresponding to ventricle depolarization), and QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with ECG findings meeting the following criteria is presented: (1) PR interval \>=300 msec; (2) QRS duration \>=200 msec; (3) QTcF interval: 450 to \<480 msec; (4) QTcF interval: 480 to \<500 msec; (5) QTcF interval \>=500 msec; (6) PR interval percent increase from baseline \>=25/50 percent; (7) QRS duration percent increase from baseline \>=50 percent; (8) QTcF interval increase from baseline: 30 to \<60 msec; (9) QTcF interval increase from baseline \>=60 msec.
Time frame: Day 5
Population: Safety analysis set included all participants who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF interval: 450 to <480 msec | 1 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | PR interval increase from baseline >=25/50 percent | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | PR interval >=300 msec | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QRS duration increase from baseline >=50 percent | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF interval: 480 to <500 msec | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF increase from baseline: 30 to <60 msec | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QRS duration >=200 msec | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF interval increase from baseline >=60 msec | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF interval >=500 msec | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF interval increase from baseline >=60 msec | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | PR interval >=300 msec | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF interval: 450 to <480 msec | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF interval: 480 to <500 msec | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF interval >=500 msec | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | PR interval increase from baseline >=25/50 percent | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QRS duration increase from baseline >=50 percent | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QTcF increase from baseline: 30 to <60 msec | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-defined Summarization Criteria | QRS duration >=200 msec | 0 participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Laboratory tests included: hematology (hemoglobin, hematocrit, red and white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, prothrombin time/international normalized ratio), chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate and alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (pH, qualitative glucose, protein, and blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, and microscopy), and other tests (follicle stimulating hormone, urine drug test and serologic tests on human immunodeficiency virus-1 antibody, Hepatitis B surface antigen and hepatitis C antibody). Abnormality was determined by the investigator using widely accepted criteria in clinical practice.
Time frame: Day 5
Population: Safety analysis set included all participants who received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moderate Hepatic Impairment Group | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 7 participants |
| Normal Hepatic Function Group | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 0 participants |
Primary
Number of Participants With Post-baseline Clinically Significant Findings in Physical Examinations
A full physical examination was performed for each participant, and it included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes and gastrointestinal, musculoskeletal, and neurological systems. Clinical significance of laboratory findings was determined by the investigator.
Time frame: Day 5
Population: Safety analysis set included all participants who received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moderate Hepatic Impairment Group | Number of Participants With Post-baseline Clinically Significant Findings in Physical Examinations | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Post-baseline Clinically Significant Findings in Physical Examinations | 0 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between administration of study medication and up to follow-up visit (28-31 days after administration) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs.
Time frame: Day 1 to follow-up visit (28-31 days after administration of study medication on Day 1)
Population: Safety analysis set included all participants who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | AEs | 1 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | AEs | 1 participants |
| Normal Hepatic Function Group | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 0 participants |
Primary
Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria
Absolute values and changes from baseline (increase and decrease) were summarized for supine diastolic blood pressure (DBP), supine systolic blood pressure (SBP), and supine pulse rate. Number of participants with vital signs findings meeting the following criteria is presented: (1) supine DBP \<50 millimeters of mercury (mm Hg); (2) supine DBP \>90 mm Hg; (3) supine SBP \<90 mm Hg; (4) supine SBP \>140 mm Hg (for normal hepatic function group); (5) supine SBP \>160 mm Hg (for moderate hepatic impairment group); (6) supine pulse rate \< 40 beats per minute (bpm); (7) supine pulse rate \>120 bpm; (8) supine DBP increase from baseline \>=20 mm Hg; (9) supine SBP increase from baseline \>=30 mmHg; (10) supine DBP decrease from baseline \>=20 mm Hg; (11) supine SBP decrease from baseline \>=30 mm Hg.
Time frame: Day 1 to Day 5
Population: Safety analysis set included all participants who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine DBP <50 mm Hg | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine DBP >90 mm Hg | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine SBP <90 mm Hg | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine SBP >160 mm Hg (moderate impairment group) | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine pulse rate <40 bpm | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine pulse rate >120 bpm | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine DBP increase from baseline >=20 mm Hg | 1 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine SBP increase from baseline >=30 mmHg | 1 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine DBP decrease from baseline >=20 mm Hg | 0 participants |
| Moderate Hepatic Impairment Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine SBP decrease from baseline >=30 mm Hg | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine SBP increase from baseline >=30 mmHg | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine DBP <50 mm Hg | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine pulse rate >120 bpm | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine DBP >90 mm Hg | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine SBP decrease from baseline >=30 mm Hg | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine SBP <90 mm Hg | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine SBP >140 mm Hg (normal function group) | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine DBP increase from baseline >=20 mm Hg | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine DBP decrease from baseline >=20 mm Hg | 0 participants |
| Normal Hepatic Function Group | Number of Participants With Vital Signs Data Meeting Pre-defined Summarization Criteria | supine pulse rate <40 bpm | 0 participants |
Primary
Total Clearance From Plasma (CL) of Rivipansel
CL of rivipansel was calculated as dose/AUCinf, where AUCinf referred to the area under the plasma concentration-time profile from time 0 extrapolated to the infinite time.
Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1
Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Total Clearance From Plasma (CL) of Rivipansel | 1.401 liter/hour | Geometric Coefficient of Variation 26 |
| Normal Hepatic Function Group | Total Clearance From Plasma (CL) of Rivipansel | 1.091 liter/hour | Geometric Coefficient of Variation 14 |
90% CI: [1.0732, 1.5372]
Secondary
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Rivipansel
Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of rivipansel was determined using a linear/log trapezoidal method.
Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1
Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Rivipansel | 593.8 hr*mcg/mL | Geometric Coefficient of Variation 26 |
| Normal Hepatic Function Group | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Rivipansel | 763.7 hr*mcg/mL | Geometric Coefficient of Variation 14 |
90% CI: [0.6493, 0.9311]
Secondary
Maximum Observed Concentration (Cmax) of Rivipansel
Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1
Population: The PK concentration population included all participants treated who had at least 1 PK concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Maximum Observed Concentration (Cmax) of Rivipansel | 77.91 mcg/mL | Geometric Coefficient of Variation 38 |
| Normal Hepatic Function Group | Maximum Observed Concentration (Cmax) of Rivipansel | 98.06 mcg/mL | Geometric Coefficient of Variation 28 |
90% CI: [0.5955, 1.0599]
Secondary
Terminal Half-Life of Rivipansel
Terminal half-life of rivipansel was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1
Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Terminal Half-Life of Rivipansel | 7.653 hours | Standard Deviation 0.964 |
| Normal Hepatic Function Group | Terminal Half-Life of Rivipansel | 7.805 hours | Standard Deviation 0.923 |
Secondary
Volume of Distribution at Steady State (Vss) of Rivipansel
Vss of rivipansel was calculated as CL\*MRT, where MRT was the mean residence time and CL was the clearance from plasma.
Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1
Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Volume of Distribution at Steady State (Vss) of Rivipansel | 14.08 liters | Geometric Coefficient of Variation 29 |
| Normal Hepatic Function Group | Volume of Distribution at Steady State (Vss) of Rivipansel | 11.20 liters | Geometric Coefficient of Variation 14 |
Other Pre-specified
Time for Maximum Observed Concentration (Tmax) of Rivipansel
Time frame: Pre-dose, 0.33, 1, 3, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post-dose on Day 1
Population: The PK parameter analysis population included all participants treated who had at least one of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate Hepatic Impairment Group | Time for Maximum Observed Concentration (Tmax) of Rivipansel | 0.667 hours |
| Normal Hepatic Function Group | Time for Maximum Observed Concentration (Tmax) of Rivipansel | 0.667 hours |