Human Immunodeficiency Virus (HIV) Infection
Conditions
Brief summary
This study will evaluate the general tolerability and pharmacokinetics (PK) of a single 60 mg dose of MK-8591 (Islatravir) in participants with severe renal insufficiency, compared to participants in good health.
Interventions
DRUGIslatravir
Single oral dose of 60 mg Islatravir administered in capsule form
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy participants must have the following: * Is in good health * Has a body mass index (BMI) ≥18.5 and ≤40 kg/m2. * Female is not pregnant or breastfeeding, and is not one of the following: a woman of childbearing potential (WOCBP); if a WOCBP, is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention Renally impaired participants must have the following: * With the exception of renal impairment, is in generally good health * Has a BMI ≥ 18.5 and ≤ 40 kg/m2 * Female is not pregnant or breastfeeding, and is not one of the following: a woman of childbearing potential (WOCBP); if a WOCBP, is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention
Exclusion criteria
Healthy participants must have the following: * 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 * Has known hypersensitivity to the active substance or any of the excipients of the study drug * Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food. * Is positive for hepatitis B surface antigen, hepatitis C antibodies or HIV. * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within prior 4 weeks * Is taking medications to treat chronic medical conditions and/or conditions associated with renal disease * Has participated in another investigational study within prior 4 weeks Other exclusions for healthy participants: * Does not agree to follow the smoking restrictions * Consumes greater than 1 glass for women, or 2 glasses for men of alcoholic beverages per day * Consumes excessive amounts,of caffeinated beverages per day. * Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately prior 3 months. Renally impaired participants must have the following: * Has a history or presence of renal artery stenosis. * Has had a renal transplant or nephrectomy. * Has rapidly fluctuating renal function as determined by historical measurements. * Has known hypersensitivity to the active substance or any of the excipients of the study drug. * Has a history of cancer (malignancy). * Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food. * Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV). * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit. * Is taking medications to treat chronic medical conditions and/or conditions associated with renal disease and has not been on a stable regimen for at least 1 month and/or is unable to withhold the use of the medication(s) within 4 hours prior to and 8 hours after administration of the study drug. * Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit. Other exclusions for renally impaired participants * Does not agree to follow the smoking restrictions. * Consumes greater than 1 glass for women, or 2 glasses for men of alcoholic beverages per day. * Consumes excessive amounts of caffeinated beverages per day. * Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Plasma Islatravir (ISL) | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 168 hours post-dose | Participants were treated with islatravir (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 Plasma ISL | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 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 Plasma ISL | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 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 of Maximum Concentration (Tmax) of Plasma ISL | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 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 (t1/2) of Plasma ISL | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 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 Clearance (CL/F) of Plasma ISL | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 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. |
| Apparent Volume of Distribution (Vz/F) of Plasma ISL | Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T1/2 of ISL-TP in PBMC | Pre-dose, 4, 24, 48, 96, 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 ISL-TP in PBMCs. The t1/2 of plasma ISL was expressed as a geometric mean. 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. |
| AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC) | Pre-dose, 4, 24, 48, 96, 168 hours post-dose | Participants were treated with ISL, and peripheral blood samples were collected from pre-dose up to 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. |
| Percentage of Participants Who Discontinued From the Study Due to an AE | Up to Day 29 | 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. |
| Percentage of Participants With an Adverse Event (AE) | Up to Day 29 | 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-last of ISL-TP in PBMC | Pre-dose, 4, 24, 48, 96, 168 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 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. |
| Cmax of ISL-TP in PBMC | Pre-dose, 4, 24, 48, 96, 168 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 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. |
| Tmax of ISL-TP in PBMC | Pre-dose, 4, 24, 48, 96, 168 hours post-dose | Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of ISL-TP in PBMCs. The Tmax of ISL-TP was expressed as a median. |
| 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. |
| 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. |
Countries
Germany, United States
Participant flow
Recruitment details
Male and females with severe renal 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 |
|---|---|
| Severe Renal Impairment Participants with severe renal impairment received a single oral dose of 60 mg Islatravir administered in capsule form. | 6 |
| Healthy Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Healthy | Total | Severe Renal Impairment |
|---|---|---|---|
| Age, Continuous | 58.8 Years STANDARD_DEVIATION 5.5 | 58.3 Years STANDARD_DEVIATION 9.5 | 57.7 Years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 3 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 | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 5 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 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Apparent Clearance (CL/F) of Plasma ISL
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, 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) |
|---|---|---|
| Severe Renal Impairment | Apparent Clearance (CL/F) of Plasma ISL | 14.2 L/hr |
| Healthy | Apparent Clearance (CL/F) of Plasma ISL | 31.3 L/hr |
Comparison: GMR90% CI: [0.35, 0.6]
Primary
Apparent Terminal Half-life (t1/2) of Plasma ISL
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, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 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 |
|---|---|---|---|
| Severe Renal Impairment | Apparent Terminal Half-life (t1/2) of Plasma ISL | 127 Hours | Geometric Coefficient of Variation 7.7 |
| Healthy | Apparent Terminal Half-life (t1/2) of Plasma ISL | 72.0 Hours | Geometric Coefficient of Variation 15.5 |
Primary
Apparent Volume of Distribution (Vz/F) of Plasma ISL
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, 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) |
|---|---|---|
| Severe Renal Impairment | Apparent Volume of Distribution (Vz/F) of Plasma ISL | 2610 Liters |
| Healthy | Apparent Volume of Distribution (Vz/F) of Plasma ISL | 3250 Liters |
Comparison: GMR90% CI: [0.56, 1.14]
Primary
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Plasma Islatravir (ISL)
Participants were treated with islatravir (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, 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) |
|---|---|---|
| Severe Renal Impairment | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Plasma Islatravir (ISL) | 14.4 hr*μM |
| Healthy | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Plasma Islatravir (ISL) | 6.54 hr*μM |
Comparison: Geometric mean ratio (GMR)90% CI: [1.68, 2.88]
Primary
Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Plasma ISL
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, 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) |
|---|---|---|
| Severe Renal Impairment | Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Plasma ISL | 11.0 hr*μM |
| Healthy | Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Plasma ISL | 5.68 hr*μM |
Comparison: GMR90% CI: [1.46, 2.55]
Primary
Maximum Concentration (Cmax) of Plasma ISL
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, 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) |
|---|---|---|
| Severe Renal Impairment | Maximum Concentration (Cmax) of Plasma ISL | 1.23 μM |
| Healthy | Maximum Concentration (Cmax) of Plasma ISL | 1.19 μM |
Comparison: GMR90% CI: [0.67, 1.57]
Primary
Time of Maximum Concentration (Tmax) of Plasma ISL
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, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 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) |
|---|---|---|
| Severe Renal Impairment | Time of Maximum Concentration (Tmax) of Plasma ISL | 1.03 Hours |
| Healthy | Time of Maximum Concentration (Tmax) of Plasma ISL | 0.75 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 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: Pre-dose, 4, 24, 48, 96, 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) |
|---|---|---|
| Severe Renal Impairment | AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC) | 5810 hr*pmol/10^6 cells |
| Healthy | AUC0-inf of ISL Triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMC) | 3920 hr*pmol/10^6 cells |
Comparison: GMR90% CI: [1.03, 2.14]
Secondary
AUC0-last of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 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: Pre-dose, 4, 24, 48, 96, 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) |
|---|---|---|
| Severe Renal Impairment | AUC0-last of ISL-TP in PBMC | 5200 hr*pmol/10^6 cells |
| Healthy | AUC0-last of ISL-TP in PBMC | 3780 hr*pmol/10^6 cells |
Comparison: GMR90% CI: [0.98, 1.93]
Secondary
Cmax of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 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: Pre-dose, 4, 24, 48, 96, 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) |
|---|---|---|
| Severe Renal Impairment | Cmax of ISL-TP in PBMC | 20.3 pmol/10^6 cells |
| Healthy | Cmax of ISL-TP in PBMC | 21.6 pmol/10^6 cells |
Comparison: GMR90% CI: [0.64, 1.39]
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. One sample was missing for a Healthy participant.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Severe Renal Impairment | Concentration at 168 Hours Post Dose (C168) of ISL-TP in PBMC | 8.06 pmol/10^6 cells |
| Healthy | Concentration at 168 Hours Post Dose (C168) of ISL-TP in PBMC | 4.43 pmol/10^6 cells |
Comparison: GMR90% CI: [0.55, 6.02]
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) |
|---|---|---|
| Severe Renal Impairment | Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC | 18.4 pmol/10^6 cells |
| Healthy | Concentration at 24 Hours Post Dose (C24) of ISL-TP in PBMC | 19.0 pmol/10^6 cells |
Comparison: GMR90% CI: [0.69, 1.35]
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) |
|---|---|---|
| Severe Renal Impairment | Concentration at 672 Hours Post Dose (C672) of ISL-TP in PBMC | 1.96 pmol/10^6 cells |
| Healthy | Concentration at 672 Hours Post Dose (C672) of ISL-TP in PBMC | 0.730 pmol/10^6 cells |
Comparison: GMR90% CI: [1.51, 4.8]
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 Day 29
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Severe Renal Impairment | Percentage of Participants Who Discontinued From the Study Due to an AE | 0.0 Percentage of participants |
| Healthy | 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 Day 29
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Severe Renal Impairment | Percentage of Participants With an Adverse Event (AE) | 16.7 Percentage of participants |
| Healthy | Percentage of Participants With an Adverse Event (AE) | 0.0 Percentage of participants |
Secondary
T1/2 of ISL-TP in PBMC
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of ISL-TP in PBMCs. The t1/2 of plasma ISL was expressed as a geometric mean. 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, 4, 24, 48, 96, 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 |
|---|---|---|---|
| Severe Renal Impairment | T1/2 of ISL-TP in PBMC | 181 Hours | Geometric Coefficient of Variation 48.4 |
| Healthy | T1/2 of ISL-TP in PBMC | 131 Hours | Geometric Coefficient of Variation 19 |
Secondary
Tmax of ISL-TP in PBMC
Participants were treated with ISL and peripheral blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of ISL-TP in PBMCs. The Tmax of ISL-TP was expressed as a median.
Time frame: Pre-dose, 4, 24, 48, 96, 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) |
|---|---|---|
| Severe Renal Impairment | Tmax of ISL-TP in PBMC | 36.00 Hours |
| Healthy | Tmax of ISL-TP in PBMC | 24.00 Hours |