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| ID | Type | Description | Link |
|---|---|---|---|
| MK-6482-020 | Other Identifier | Merck |
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The primary purpose of this study is to compare the plasma pharmacokinetics (PK) of belzutifan (MK-6482) following a single oral 80 mg dose of belzutifan in participants with moderate hepatic impairment to that of healthy matched control participants. This study will also evaluate the safety and tolerability of a single oral 80 mg dose of belzutifan in participants with moderate hepatic impairment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Moderate Hepatic Impairment | Experimental | Participants with moderate hepatic impairment will receive a single oral 80 mg dose of belzutifan on Day 1. |
|
| Healthy | Experimental | Participants with normal hepatic function will receive a single oral 80 mg dose of belzutifan on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Belzutifan | Drug | Two 40 mg tablets given as a single oral 80 mg dose. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Belzutifan | AUC0-Inf was defined as the area under the concentration-time curve of belzutifan from time zero to infinity. Blood samples collected predose and at multiple timepoints postdose were used to determine AUC0-Inf of belzutifan. | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose |
| Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24hrs) of Belzutifan | AUC0-24hrs was defined as the area under the concentration-time curve of belzutifan from time zero to 24 hours postdose. Blood samples collected predose and at multiple timepoints postdose were used to determine AUC0 to 24 hours of belzutifan. | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24 hours postdose |
| Maximum Plasma Concentration (Cmax) of Belzutifan | Cmax was defined as the peak level belzutifan reaches in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine Cmax of belzutifan. | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose |
| Time to Maximum Plasma Concentration (Tmax) of Belzutifan | Tmax was defined as the time it took belzutifan to reach its peak level in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine the Tmax of belzutifan. | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose |
| Apparent Terminal Half-life (t1/2) of Belzutifan | Apparent terminal half-life (t1/2) was defined as the time needed to reduce the level of belzutifan in the blood by one-half (1/2). Blood samples collected predose and at multiple timepoints postdose were used to determine the apparent terminal half-life (t1/2) of belzutifan. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experience 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 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. The number of participants who experienced an AE is reported. |
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Inclusion Criteria:
All Participants:
For Participants With Normal Hepatic Function:
Male Participants -Must have been vasectomized or surgically sterilized for at least 4 months or more prior to study intervention administration and agree to the following during the intervention period and for at least 5 days after administration of study intervention, be abstinent from heterosexual intercourse as their preferred and usual lifestyle or must agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
Female Participants
-Is a woman of non-childbearing potential (WONCBP).
For Participants With Moderate Hepatic Impairment
Male Participants -Have been vasectomized or surgically sterilized for at least 4 months or more prior to study intervention administration and agree to the following during the intervention period and for at least 5 days after administration of study intervention, be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
Female Participants
- Must be a WONCBP.
Exclusion Criteria:
All Participants:
For Participants with Normal Hepatic Function
For Participants With Moderate Hepatic Impairment
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orlando Clinical Research Center ( Site 0001) | Orlando | Florida | 32809 | United States | ||
| The Texas Liver Institute ( Site 0002) |
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| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1. |
| FG001 | Healthy | Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1. |
| BG001 | Healthy | Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Belzutifan | AUC0-Inf was defined as the area under the concentration-time curve of belzutifan from time zero to infinity. Blood samples collected predose and at multiple timepoints postdose were used to determine AUC0-Inf of belzutifan. | All participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, who have available measurement data, and have no important protocol deviations. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose |
|
Up to 15 days
All Cause Mortality is reported for all allocated participants. Serious Adverse Events and Other Adverse Events are reported for all participants who received treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral 80 mg dose of belzutifan on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspepsia | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@msd.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 24, 2022 | Nov 21, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C000720612 | belzutifan |
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Parallel Group
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| Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose |
| Up to 15 days |
| Number of Participants Who Discontinue Study Treatment 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 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. The number of participants who discontinued the study due to an AE is reported. | Up to 15 days |
| San Antonio |
| Texas |
| 78215 |
| United States |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Healthy | Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1. |
|
|
|
| Primary | Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24hrs) of Belzutifan | AUC0-24hrs was defined as the area under the concentration-time curve of belzutifan from time zero to 24 hours postdose. Blood samples collected predose and at multiple timepoints postdose were used to determine AUC0 to 24 hours of belzutifan. | All participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, who have available measurement data, and have no important protocol deviations. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24 hours postdose |
|
|
|
|
| Primary | Maximum Plasma Concentration (Cmax) of Belzutifan | Cmax was defined as the peak level belzutifan reaches in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine Cmax of belzutifan. | All participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, who have available measurement data, and have no important protocol deviations. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose |
|
|
|
|
| Primary | Time to Maximum Plasma Concentration (Tmax) of Belzutifan | Tmax was defined as the time it took belzutifan to reach its peak level in the blood. Blood samples collected predose and at multiple timepoints postdose were used to determine the Tmax of belzutifan. | All participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, who have available measurement data, and have no important protocol deviations. | Posted | Median | Full Range | hr | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose |
|
|
|
| Primary | Apparent Terminal Half-life (t1/2) of Belzutifan | Apparent terminal half-life (t1/2) was defined as the time needed to reduce the level of belzutifan in the blood by one-half (1/2). Blood samples collected predose and at multiple timepoints postdose were used to determine the apparent terminal half-life (t1/2) of belzutifan. | All participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, who have available measurement data, and have no important protocol deviations. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 72, 96, and 120 hours postdose |
|
|
|
| Secondary | Number of Participants Who Experience 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 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. The number of participants who experienced an AE is reported. | All participants who were allocated and received study treatment. | Posted | Count of Participants | Participants | Up to 15 days |
|
|
|
| Secondary | Number of Participants Who Discontinue Study Treatment 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 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. The number of participants who discontinued the study due to an AE is reported. | All participants who were allocated and received study treatment. | Posted | Count of Participants | Participants | Up to 15 days |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 1 |
| 9 |
| EG001 | Healthy Matched Control | Participants with normal hepatic function received a single oral 80 mg dose of belzutifan on Day 1. | 0 | 8 | 0 | 8 | 1 | 8 |
| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
The Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. A coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors authorship requirements.