Parkinson Disease
Conditions
Brief summary
This is a two part study to compare the PK of preladenant administered to participants with CRI to the PK of preladenant administered to healthy participants. Part 1 will compare the PK of participants with severe CRI to healthy participants. Part 2 will compare the PK of participants with moderate CRI and participants with mild CRI to healthy participants. The primary hypotheses are that the plasma area under the concentration-time curve from time 0 to infinity after single dosing (AUC0-∞) of preladenant in participants with either severe, moderate or mild CRI is similar to that of matched healthy participants.
Interventions
DRUGPreladenant
After an overnight fast, a single 5 mg dose, (1 x 5 mg tablet) was administered orally
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
* Has a body mass index (BMI) between 19 to 34 kg/m\^2, inclusive * Has mild to severe CRI and not on dialysis (Participants with normal renal function are to be matched to subjects with renal impairment) * Clinical laboratory tests, electrocardiogram, and vital signs within normal ranges * Free of any clinically significant disease that would interfere with the study evaluations (except related to his/her renal disease and comorbid conditions)
Exclusion criteria
* Females who are pregnant, intend to become pregnant (within 3 months of ending the study), or are nursing/breastfeeding * Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug * Had a renal transplant or are on dialysis * Has a history of any infectious disease within 4 weeks * Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV) * Has donated blood or had a blood transfusions in the past 60 days * Has demonstrated allergic reactions (eg, food, drug, atopic reactions or asthmatic episodes) which could interfere with their ability to participate in the trial * Has a history of malignancy * Has evidence of suicidality or is at risk for self-harm or harm to others
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) After Single Dosing With Preladenant for Participants With Severe CRI Versus Healthy Matched Controls | Pre-dose to 48 hours post-dose | Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant |
| AUC0-∞ After Single Dosing With Preladenant for Participants With Moderate CRI Versus Healthy Matched Controls | Pre-dose to 48 hours post-dose | Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant |
| AUC0-∞ After Single Dosing With Preladenant for Participants With Mild CRI Versus Healthy Matched Controls | Pre-dose to 48 hours post-dose | Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant |
Participant flow
Recruitment details
Male or female adults with different degrees of renal impairment along with matched healthy adults with normal renal function were selected for this study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Severe Renal Impairment Participants with severe CRI, defined as creatinine clearance of \<30 mL/min/1.73 m\^2, were treated with a single tablet of 5 mg preladenant, administered orally | 9 |
| Part 2: Moderate Renal Impairment Participants with moderate CRI defined as creatinine clearance of ≥30 and \<50 mL/min/1.73 m\^2, were treated with a single tablet of 5 mg preladenant, administered orally | 9 |
| Part 2: Mild Renal Impairment Participants with mild CRI, defined as creatinine clearance of ≥50 and ≤80 mL/min/1.73m\^2, were treated with a single tablet of 5 mg preladenant, administered orally | 8 |
| Part 1: Normal Renal Function Participants with normal renal function, defined as creatinine clearance of \>80 mL/min/1.73 m\^2, were treated with a single tablet of 5 mg preladenant, administered orally | 9 |
| Part 2: Normal Renal Function Participants with normal renal function, defined as creatinine clearance of \>80 mL/min/1.73 m\^2, were treated with a single tablet of 5 mg preladenant, administered orally | 11 |
| Total | 46 |
Baseline characteristics
| Characteristic | Part 1: Severe Renal Impairment | Part 2: Moderate Renal Impairment | Part 2: Mild Renal Impairment | Part 1: Normal Renal Function | Part 2: Normal Renal Function | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 59.6 Years STANDARD_DEVIATION 12.4 | 66.9 Years STANDARD_DEVIATION 7.8 | 63.3 Years STANDARD_DEVIATION 7.6 | 59.3 Years STANDARD_DEVIATION 11.3 | 67.4 Years STANDARD_DEVIATION 4 | 63.5 Years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 5 Participants | 3 Participants | 5 Participants | 20 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 3 Participants | 6 Participants | 6 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 9 | 1 / 8 | 0 / 9 | 0 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 8 | 0 / 9 | 0 / 11 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) After Single Dosing With Preladenant for Participants With Severe CRI Versus Healthy Matched Controls
Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant
Time frame: Pre-dose to 48 hours post-dose
Population: Four participants with severe CRI, and two matched healthy participants with insufficient terminal phase data to allow adequate characterization, were not analyzed. As only participants with severe CRI are presented, participants with mild or moderate CRI or their corresponding healthy matched controls were not analyzed in this outcome measure
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Severe Renal Impairment | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) After Single Dosing With Preladenant for Participants With Severe CRI Versus Healthy Matched Controls | 160.53 ng.hr/mL |
| Part 1: Normal Renal Function | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) After Single Dosing With Preladenant for Participants With Severe CRI Versus Healthy Matched Controls | 135.12 ng.hr/mL |
90% CI: [0.54, 2.62]
Primary
AUC0-∞ After Single Dosing With Preladenant for Participants With Mild CRI Versus Healthy Matched Controls
Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant
Time frame: Pre-dose to 48 hours post-dose
Population: One participant with mild CRI, and two matched healthy participants with insufficient terminal phase data to allow adequate characterization, were not analyzed. As only participants with mild CRI are presented, participants with severe or moderate CRI or their corresponding healthy matched controls were not analyzed in this outcome measure
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 2: Mild Renal Impairment | AUC0-∞ After Single Dosing With Preladenant for Participants With Mild CRI Versus Healthy Matched Controls | 275.50 ng.hr/mL |
| Part 2: Normal Renal Function | AUC0-∞ After Single Dosing With Preladenant for Participants With Mild CRI Versus Healthy Matched Controls | 104.66 ng.hr/mL |
90% CI: [1.38, 5.04]
Primary
AUC0-∞ After Single Dosing With Preladenant for Participants With Moderate CRI Versus Healthy Matched Controls
Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant
Time frame: Pre-dose to 48 hours post-dose
Population: One participant with moderate CRI, and two matched healthy participants with insufficient terminal phase data to allow adequate characterization, were not analyzed. As only participants with moderate CRI are presented, participants with mild or severe CRI or their corresponding healthy matched controls were not analyzed in this outcome measure
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 2: Moderate Renal Impairment | AUC0-∞ After Single Dosing With Preladenant for Participants With Moderate CRI Versus Healthy Matched Controls | 197.43 ng.hr/mL |
| Part 2: Normal Renal Function | AUC0-∞ After Single Dosing With Preladenant for Participants With Moderate CRI Versus Healthy Matched Controls | 152.18 ng.hr/mL |
90% CI: [0.59, 2.87]