Human Immunodeficiency Virus (HIV) Infection
Conditions
Brief summary
This is an open-label, single-dose study of the plasma pharmacokinetics (PK), safety, and tolerability of islatravir (ISL, MK-8591), and the intracellular PK of ISL triphosphate (ISL-TP) in male and female adult participants with moderate hepatic impairment and in healthy matched control participants.
Interventions
DRUGIslatravir
Two ISL 30 mg capsules taken by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy Control Participants: * Is in good health based on medical history, physical examination, vital sign (VS) measurements and electrocardiograms (ECGs) performed prior to randomization * Is in good health based on laboratory safety tests obtained at the screening visit and prior to administration of the initial dose of study drug. * Has a body mass index (BMI) ≥18.5 and ≤40 kg/m2 Hepatic Impairment Participants: * Has a diagnosis of chronic (\> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology * Has a score on the Child-Pugh scale ranging from 7 to 9 (moderate hepatic insufficiency) at screening * With the exception of hepatic impairment, is in generally good health * Has a BMI ≥ 18.5 and ≤ 40 kg/m2 Healthy and Hepatic Impairment Participants: * Males : uses contraception according to local regulations * Females: is not pregnant or breastfeeding and one of the following applies: * Is not a woman of childbearing potential (WOCBP) OR * Is a WOCBP and uses an acceptable contraceptive method * A WOCBP with negative highly sensitive pregnancy test within 24 hours of study intervention
Exclusion criteria
* Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases * Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years * Has a history of cancer (malignancy) * Has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or non-prescription drugs or food * Has known hypersensitivity to the active substance or any of the excipients of the study drug * Is positive for hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or HIV-2 * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit * Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to study drug administration, throughout the study, until the poststudy visit * Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit * Has a QTc interval \>470 for males or \>480 ms for females, has a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), has uncorrected hypokalemia or hypomagnesemia, is taking concomitant medications that prolong the QT/QTc interval * Is not considered low risk of having HIV infection * Is a smoker or user of electronic cigarettes and/or has used nicotine or nicotine-containing products (eg, nicotine patch) within 3 months of screening * Consumes greater than 3 glasses of alcoholic beverages per day * Consumes more than 6 caffeinated beverages per day * Is a regular user of illicit drugs or has a history of drug abuse within 2 years * Presents any concern to the investigator regarding safe study participation * Is unwilling to comply with study restrictions * Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose | Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
| Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of ISL in Plasma | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose | Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
| Maximum Concentration (Cmax) of ISL in Plasma | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose | Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
| Time to Maximum Concentration (Tmax) of ISL in Plasma | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose | Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Tmax of plasma ISL was expressed as a median. |
| Apparent Terminal Half-Life (t½) of ISL in Plasma | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose | Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100. |
| Apparent Total Clearance (CL/F) of ISL in Plasma | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose | Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100. |
| Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL in Plasma | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose | Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration at 672 Hours Post Dose (C672) of ISL-TP in PBMC | 672 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected at 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
| Percentage of Participants With an Adverse Event (AE) | Up to 28 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| T1/2 of ISL-TP in PBMC | Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose | Participants were treated with ISL, and peripheral blood samples were collected from pre-dose to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100. |
| Tmax of ISL-TP in PBMC | Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The Tmax of ISL-TP was expressed as a median. |
| Percentage of Participants Who Discontinued From the Study Due to an AE | Up to 28 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC) | Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose | Participants were treated with ISL, and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
| AUC0-last of ISL-TP in PBMC | Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
| Cmax of ISL-TP in PBMC | Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
| Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC | 24 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected at 24 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
| Concentration at 168 Hours Post Dose (C168) of ISL-TP in PBMC | 168 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected at 168 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values. |
Countries
United States
Participant flow
Recruitment details
Male and females with moderate hepatic impairment between the ages of 18 and 75 years old (inclusive), and healthy matched controls were enrolled in this study
Participants by arm
| Arm | Count |
|---|---|
| Participants With Moderate Hepatic Impairment Participants with moderate hepatic impairment received a single oral dose of 60 mg Islatravir administered in capsule form. | 6 |
| Healthy Matched Control Participants Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Healthy Matched Control Participants | Total | Participants With Moderate Hepatic Impairment |
|---|---|---|---|
| Age, Continuous | 59.5 Years STANDARD_DEVIATION 6.6 | 60.0 Years STANDARD_DEVIATION 7.8 | 60.5 Years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 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 | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Apparent Terminal Half-Life (t½) of ISL in Plasma
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Moderate Hepatic Impairment | Apparent Terminal Half-Life (t½) of ISL in Plasma | 72.9 Hours | Geometric Coefficient of Variation 13.6 |
| Healthy Matched Control Participants | Apparent Terminal Half-Life (t½) of ISL in Plasma | 83.9 Hours | Geometric Coefficient of Variation 12 |
Primary
Apparent Total Clearance (CL/F) of ISL in Plasma
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Moderate Hepatic Impairment | Apparent Total Clearance (CL/F) of ISL in Plasma | 35.1 Liters/Hour | Geometric Coefficient of Variation 12.9 |
| Healthy Matched Control Participants | Apparent Total Clearance (CL/F) of ISL in Plasma | 26.5 Liters/Hour | Geometric Coefficient of Variation 30.3 |
Primary
Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL in Plasma
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Moderate Hepatic Impairment | Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL in Plasma | 3714 Liters | Geometric Coefficient of Variation 18.4 |
| Healthy Matched Control Participants | Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL in Plasma | 3197 Liters | Geometric Coefficient of Variation 38.6 |
Primary
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma | 5.81 Hours*μmol/Liter |
| Healthy Matched Control Participants | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Islatravir (ISL) in Plasma | 7.74 Hours*μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.58, 0.96]
Primary
Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of ISL in Plasma
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of ISL in Plasma | 5.25 Hours*μmol/Liter |
| Healthy Matched Control Participants | Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of ISL in Plasma | 6.97 Hours*μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.58, 0.98]
Primary
Maximum Concentration (Cmax) of ISL in Plasma
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Maximum Concentration (Cmax) of ISL in Plasma | 0.834 μmol/Liter |
| Healthy Matched Control Participants | Maximum Concentration (Cmax) of ISL in Plasma | 1.28 μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.38, 1.14]
Primary
Time to Maximum Concentration (Tmax) of ISL in Plasma
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Tmax of plasma ISL was expressed as a median.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Time to Maximum Concentration (Tmax) of ISL in Plasma | 1.00 Hours |
| Healthy Matched Control Participants | Time to Maximum Concentration (Tmax) of ISL in Plasma | 1.00 Hours |
Secondary
AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC)
Participants were treated with ISL, and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC) | 19500 hours*μmol/Liter |
| Healthy Matched Control Participants | AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC) | 25700 hours*μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.57, 1]
Secondary
AUC0-last of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | AUC0-last of ISL-TP in PBMC | 18600 hours*μmol/Liter |
| Healthy Matched Control Participants | AUC0-last of ISL-TP in PBMC | 24100 hours*μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.58, 1.03]
Secondary
Cmax of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Cmax of ISL-TP in PBMC | 109 μmol/Liter |
| Healthy Matched Control Participants | Cmax of ISL-TP in PBMC | 113 μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.63, 1.46]
Secondary
Concentration at 168 Hours Post Dose (C168) of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected at 168 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: 168 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Concentration at 168 Hours Post Dose (C168) of ISL-TP in PBMC | 39.9 μmol/Liter |
| Healthy Matched Control Participants | Concentration at 168 Hours Post Dose (C168) of ISL-TP in PBMC | 46.4 μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.59, 1.26]
Secondary
Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected at 24 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: 24 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC | 103 μmol/Liter |
| Healthy Matched Control Participants | Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC | 97.6 μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.65, 1.71]
Secondary
Concentration at 672 Hours Post Dose (C672) of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected at 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Time frame: 672 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Concentration at 672 Hours Post Dose (C672) of ISL-TP in PBMC | 3.80 μmol/Liter |
| Healthy Matched Control Participants | Concentration at 672 Hours Post Dose (C672) of ISL-TP in PBMC | 5.82 μmol/Liter |
Comparison: Geometric least-squares mean ratio (GMR)90% CI: [0.42, 1.01]
Secondary
Percentage of Participants Who Discontinued From the Study Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to 28 days
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Percentage of Participants Who Discontinued From the Study Due to an AE | 0.0 Percentage of participants |
| Healthy Matched Control Participants | Percentage of Participants Who Discontinued From the Study Due to an AE | 0.0 Percentage of participants |
Secondary
Percentage of Participants With an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to 28 days
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Percentage of Participants With an Adverse Event (AE) | 16.7 Percentage of participants |
| Healthy Matched Control Participants | Percentage of Participants With an Adverse Event (AE) | 16.7 Percentage of participants |
Secondary
T1/2 of ISL-TP in PBMC
Participants were treated with ISL, and peripheral blood samples were collected from pre-dose to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.
Time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Moderate Hepatic Impairment | T1/2 of ISL-TP in PBMC | 148 Hours | Geometric Coefficient of Variation 18.4 |
| Healthy Matched Control Participants | T1/2 of ISL-TP in PBMC | 169 Hours | Geometric Coefficient of Variation 31.9 |
Secondary
Tmax of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 672 hours post-dose to determine the concentration of ISL-TP in PBMCs. The Tmax of ISL-TP was expressed as a median.
Time frame: Predose and 4, 24, 48, 96, 168, 240, 336, 408, 504, and 672 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of important protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With Moderate Hepatic Impairment | Tmax of ISL-TP in PBMC | 24.00 Hours |
| Healthy Matched Control Participants | Tmax of ISL-TP in PBMC | 48.00 Hours |