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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3814-034 | Other Identifier | Merck & Co. |
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The purpose of this study is to compare the pharmacokinetics (PK) of preladenant after administration of a single 5 mg oral dose of preladenant in participants with hepatic impairment and healthy volunteers. Part 1 of this study compares healthy volunteers with participants with mild hepatic impairment. Part 2 compares healthy volunteers with participants with moderate hepatic impairment. Healthy volunteers in each part of this study are to be matched with participants with hepatic impairment by race, age, gender, and body mass index (BMI). The primary hypotheses are that in participants with mild or moderate HI, the area under the concentration-time curve from time 0 extrapolated to time of the last quantifiable concentration (AUC0-t) of preladenant is similar to that observed in matched healthy volunteers, so that the mean ratio of hepatic impaired/healthy is contained within the interval [0.50, 2.00].
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mild Hepatic Impaired (HI) Part 1 | Experimental | Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
|
| Healthy to Match Mild HI Part 1 | Active Comparator | Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
|
| Moderate HI Part 2 | Experimental | Participants with moderate chronic liver disease enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1. |
|
| Healthy to Match Moderate HI Part 2 | Active Comparator | Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Preladenant | Drug | After at least an 8 hours overnight fast, one 5-mg preladenant tablet, is administered orally, on Day 1. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUC 0-t) of Preladenant After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant. | Pre-dose up to 72 hours postdose |
| Maximum Observed Plasma Concentration (Cmax) of Preladenant After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant. | Pre-dose up to 72 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| AUC 0-t of Preladenant Metabolite SCH 434748 After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of SCH 434748. | Pre-dose up to 72 hours postdose |
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Key Inclusion Criteria for Healthy Participants Groups:
Key Inclusion Criteria for Hepatic Impaired Groups:
Key Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| ID | Title | Description |
|---|---|---|
| FG000 | Mild Hepatic Impaired (HI) Part 1 | Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
| FG001 | Healthy to Match Mild HI Part 1 | Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
| FG002 | Moderate HI Part 2 | Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1. |
| FG003 | Healthy to Match Moderate HI Part 2 | Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Randomized participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Mild Hepatic Impaired (HI) Part 1 | Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
| BG001 | Healthy to Match Mild HI Part 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 Plasma Concentration-time Curve From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUC 0-t) of Preladenant After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant. | All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics. | Posted | Least Squares Mean | Full Range | hr*ng/mL | Pre-dose up to 72 hours postdose |
|
Up to 7 days
All participants who received an oral dose of preladenant.
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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 | Mild Hepatic Impaired (HI) Part 1 | Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C539997 | 2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine |
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|
| Cmax of Preladenant Metabolite SCH 434748 After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of SCH 434748. | Pre-dose up to 72 hours postdose |
| AUC 0-t of Preladenant Metabolite SCH 446637 After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of SCH 446637. | Pre-dose up to 72 hours postdose |
| Cmax of Preladenant Metabolite SCH 446637 After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of SCH 446637. | Pre-dose up to 72 hours postdose |
| AUC 0-t of Preladenant Calculated Using Free Drug Concentration After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant calculated using free drug concentration. | Pre-dose up to 72 hours postdose |
| Cmax of Preladenant Calculated Using Free Drug Concentration After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant calculated using free drug concentration. | Pre-dose up to 72 hours postdose |
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
| BG002 | Moderate HI Part 2 | Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1. |
| BG003 | Healthy to Match Moderate HI Part 2 | Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Healthy to Match Mild HI Part 1 | Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
| OG002 | Moderate HI Part 2 | Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1. |
| OG003 | Healthy to Match Moderate HI Part 2 | Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1. |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Preladenant After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant. | All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics. | Posted | Least Squares Mean | Full Range | ng/mL | Pre-dose up to 72 hours postdose |
|
|
|
|
| Secondary | AUC 0-t of Preladenant Metabolite SCH 434748 After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of SCH 434748. | All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics. | Posted | Least Squares Mean | Full Range | hr*ng/mL | Pre-dose up to 72 hours postdose |
|
|
|
|
| Secondary | Cmax of Preladenant Metabolite SCH 434748 After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of SCH 434748. | All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics. | Posted | Least Squares Mean | Full Range | ng/mL | Pre-dose up to 72 hours postdose |
|
|
|
|
| Secondary | AUC 0-t of Preladenant Metabolite SCH 446637 After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of SCH 446637. | All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics. | Posted | Least Squares Mean | Full Range | hr*ng/mL | Pre-dose up to 72 hours postdose |
|
|
|
|
| Secondary | Cmax of Preladenant Metabolite SCH 446637 After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of SCH 446637. | All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics. | Posted | Least Squares Mean | Full Range | ng/mL | Pre-dose up to 72 hours postdose |
|
|
|
|
| Secondary | AUC 0-t of Preladenant Calculated Using Free Drug Concentration After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant calculated using free drug concentration. | All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics. | Posted | Least Squares Mean | Full Range | hr*ng/mL | Pre-dose up to 72 hours postdose |
|
|
|
|
| Secondary | Cmax of Preladenant Calculated Using Free Drug Concentration After a Single Dose of Preladenant | For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant calculated using free drug concentration. | All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics. | Posted | Least Squares Mean | Full Range | ng/mL | Pre-dose up to 72 hours postdose |
|
|
|
|
| 0 |
| 12 |
| 2 |
| 12 |
| EG001 | Healthy to Match Mild HI Part 1 | Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. | 0 | 12 | 0 | 12 |
| EG002 | Moderate HI Part 2 | Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1. | 0 | 9 | 1 | 9 |
| EG003 | Healthy to Match Moderate HI Part 2 | Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1. | 0 | 9 | 1 | 9 |
| Toothache | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dyskinesia | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with regard to proprietary information; the accuracy of the information; and to ensure that the presentation is fairly balanced and in compliance with Food and Drug Administration (FDA) regulations.
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| The analysis was performed using an ANCOVA model. Parameters were log-transformed (using the natural logarithm) prior to analysis. Study population (i.e., HI or Healthy) was included as a fixed effect with continuous covariates age, BMI and a categorical covariate, gender. Gender was included from Part 2 analysis. | LSM Ratio | 1.434 | 2-Sided | 90 | 0.643 | 3.198 | Non-Inferiority or Equivalence | To be considered equivalent the LSM Ratio (HI/Healthy) is contained within the interval [0.50, 2.00]. |
| The analysis was performed using an ANCOVA model. Parameters were log-transformed (using the natural logarithm) prior to analysis. Study population (i.e., HI or Healthy) was included as a fixed effect with continuous covariates age, BMI and a categorical covariate, gender. Gender was included from Part 2 analysis. | LSM Ratio | 2.392 | 2-Sided | 90 | 1.306 | 4.382 | Non-Inferiority or Equivalence | To be considered equivalent the LSM Ratio (HI/Healthy) is contained within the interval [0.50, 2.00]. |
| The analysis was performed using an ANCOVA model. Parameters were log-transformed (using the natural logarithm) prior to analysis. Study population (i.e., HI or Healthy) was included as a fixed effect with continuous covariates age, BMI and a categorical covariate, gender. Gender was included from Part 2 analysis. | LSM Ratio | 1.407 | 2-Sided | 90 | 0.720 | 2.750 | Non-Inferiority or Equivalence | To be considered equivalent the LSM Ratio (HI/Healthy) is contained within the interval [0.50, 2.00]. |
| The analysis was performed using an ANCOVA model. Parameters were log-transformed (using the natural logarithm) prior to analysis. Study population (i.e., HI or Healthy) was included as a fixed effect with continuous covariates age, BMI and a categorical covariate, gender. Gender was included from Part 2 analysis. | LSM Ratio | 4.806 | 2-Sided | 90 | 2.770 | 8.335 | Non-Inferiority or Equivalence | To be considered equivalent the LSM Ratio (HI/Healthy) is contained within the interval [0.50, 2.00]. |
| The analysis was performed using an ANCOVA model. Parameters were log-transformed (using the natural logarithm) prior to analysis. Study population (i.e., HI or Healthy) was included as a fixed effect with continuous covariates age, BMI and a categorical covariate, gender. Gender was included from Part 2 analysis. | LSM Ratio | 1.980 | 2-Sided | 90 | 1.316 | 2.977 | Non-Inferiority or Equivalence | To be considered equivalent the LSM Ratio (HI/Healthy) is contained within the interval [0.50, 2.00]. |
| The analysis was performed using an ANCOVA model. Parameters were log-transformed (using the natural logarithm) prior to analysis. Study population (i.e., HI or Healthy) was included as a fixed effect with continuous covariates age, BMI and a categorical covariate, gender. Gender was included from Part 2 analysis. | LSM Ratio | 4.041 | 2-Sided | 90 | 1.460 | 11.187 | Non-Inferiority or Equivalence | To be considered equivalent the LSM Ratio (HI/Healthy) is contained within the interval [0.50, 2.00]. |
| The analysis was performed using an ANCOVA model. Parameters were log-transformed (using the natural logarithm) prior to analysis. Study population (i.e., HI or Healthy) was included as a fixed effect with continuous covariates age, BMI and a categorical covariate, gender. Gender was included from Part 2 analysis. | LSM Ratio | 2.231 | 2-Sided | 90 | 0.844 | 5.896 | Non-Inferiority or Equivalence | To be considered equivalent the LSM Ratio (HI/Healthy) is contained within the interval [0.50, 2.00]. |