Insomnia
Conditions
Brief summary
This study will investigate whether the plasma concentration-time profile and pharmacokinetics (PK) of suvorexant (MK-4305) in participants with impaired renal function are similar to those observed in healthy participants; and will evaluate the safety and tolerability of suvorexant both in participants with impaired renal function and in healthy participants.
Detailed description
Study Design: This study plans to enroll 16 participants in Part I (8 participants with severe renal impairment and a control group of 8 healthy participants) and 32 participants in Part II (8 participants with moderate renal impairment and a control group of 8 healthy participants; and 8 participants with mild renal impairment and a control group of 8 healthy participants). Part II will be conducted only if the primary hypothesis is not met in Part I and there is a significant difference in the PK of suvorexant between healthy participants and severe renal impairment participants.
Interventions
DRUGSuvorexant
single oral dose of 20 mg (administered as 2 x 10 mg tablets) of suvorexant administered with \ 240 mL of water after an 8 hour fast
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 70 Years
Healthy volunteers
Yes
Inclusion criteria
Impaired Renal Function Participants: * Females of reproductive potential must have a negative pregnancy test and agree to use (and/or have their partner use) two acceptable methods of birth control * Body Mass Index (BMI) ≤40 kg/m\^2 * Diagnosis of renal insufficiency Healthy Participants: * Females of reproductive potential must have a negative pregnancy test and agree to use (and/or have their partner use) two acceptable methods of birth control * Body Mass Index (BMI) ≤40 kg/m\^2 and is matched for BMI ± 5 units to his/her corresponding renal participant * In general good health * Matched for age ± 10 years to his/her corresponding renal participant
Exclusion criteria
Impaired Renal Function Participants: * Is mentally or legally incapacitated * History of a clinically significant psychiatric disorder over the last year * Has rapidly fluctuating renal function or has demonstrated or suspected renal artery stenosis * Has had a kidney transplant * Unstable endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases * History of cancer (Some exceptions apply) * Regular user of barbiturates or sleep aides * Consumes excessive amounts of alcohol (\>2 drinks/day) * Consumes excessive amounts of caffeinated beverages (\>6/day) * Has had major surgery within 4 weeks * Has a history of significant multiple and/or severe allergies * Has a history of cataplexy * Participant works a night shift and is not able to avoid night shift work during the study * Current or history of illicit drug abuse * Nursing mothers Healthy Participants: * Is mentally or legally incapacitated; * Has a history of stroke, chronic seizures, or major neurological disorder * Unstable endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases * History of cancer (Some exceptions apply) * Regular user of barbiturates or sleep aides * Consumes excessive amounts of alcohol (\>2 drinks/day) * Consumes excessive amounts of caffeinated beverages (\>6/day) * Has had major surgery within 4 weeks * Has a history of significant multiple and/or severe allergies * Has a history of cataplexy * Participant works a night shift and is not able to avoid night shift work during the study * Current or history of illicit drug abuse * Nursing mothers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-∞) After Single Dose Suvorexant: Severe Renal Impairment Participants Versus Healthy Participants (Part I) | Predose and 0.5, 1, 2, 4, 6, 9, 12, 16, 24, 48, 72, 96, and 120 hours post-dose | Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and the extrapolated area given by the quotient of the last detectable concentration and the apparent terminal rate constant (λ). |
| AUC(0-∞) After Single Dose Suvorexant: Moderate and Mild Renal Impairment Participants Versus Healthy Participants (Part II) | Predose and 0.5, 1, 2, 4, 6, 9, 12, 16, 24, 48, 72, 96, and 120 hours post-dose | Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and the extrapolated area given by the quotient of the last detectable concentration and the apparent terminal rate constant (λ). |
| Number of Participants With an Adverse Event (AE) | From administration of study drug through 14 days after administration of study drug | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. |
| Number of Participants Who Discontinued Study Due to an AE | From administration of study drug through 14 days after administration of study drug | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. |
Participant flow
Pre-assignment details
16 participants were enrolled in Part I of the study. Because the primary hypothesis was met in Part I, no participants were enrolled in Part II of the study.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Severe Renal Impairment (Part I) Participants with severe renal impairment received a
single dose of 20 mg open-label suvorexant. | 8 |
| Healthy Participants (Part I) Healthy participants matched to participants with severe renal impairment received a single dose of 20 mg open-label suvorexant. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Participants With Severe Renal Impairment (Part I) | Healthy Participants (Part I) | Total |
|---|---|---|---|
| Age, Continuous | 50.6 years STANDARD_DEVIATION 12.5 | 48.1 years STANDARD_DEVIATION 11.6 | 49.4 years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 8 | 4 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-∞) After Single Dose Suvorexant: Severe Renal Impairment Participants Versus Healthy Participants (Part I)
Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and the extrapolated area given by the quotient of the last detectable concentration and the apparent terminal rate constant (λ).
Time frame: Predose and 0.5, 1, 2, 4, 6, 9, 12, 16, 24, 48, 72, 96, and 120 hours post-dose
Population: All Treated Participants
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Severe Renal Impairment (Part I) | Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-∞) After Single Dose Suvorexant: Severe Renal Impairment Participants Versus Healthy Participants (Part I) | 11.98 μM•hr |
| Healthy Participants (Part I) | Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-∞) After Single Dose Suvorexant: Severe Renal Impairment Participants Versus Healthy Participants (Part I) | 9.81 μM•hr |
Comparison: The geometric mean (GM) for each participant group and the corresponding 95% confidence interval (CI) were calculated for AUC(0-∞) using an analysis of covariance (ANCOVA) model.~The AUC(0-∞) geometric mean ratio (GMR) of the 2 participant groups was used to test the primary hypothesis, which was that the AUC(0-∞) of suvorexant following a single oral dose would be similar between participants with renal impairment and healthy matched control participants.90% CI: [0.93, 1.6]ANCOVA
Primary
AUC(0-∞) After Single Dose Suvorexant: Moderate and Mild Renal Impairment Participants Versus Healthy Participants (Part II)
Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and the extrapolated area given by the quotient of the last detectable concentration and the apparent terminal rate constant (λ).
Time frame: Predose and 0.5, 1, 2, 4, 6, 9, 12, 16, 24, 48, 72, 96, and 120 hours post-dose
Population: Per protocol, the decision to conduct Part II of study in moderate/mild renal impairment participants was conditional on results of AUC (0-∞) analysis in severe renal impairment participants (Part I). Based on results of Part I of study, Part II was not conducted and AUC(0-∞) analysis in moderate/mild renal impairment was not done.
Primary
Number of Participants Who Discontinued Study Due to an AE
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.
Time frame: From administration of study drug through 14 days after administration of study drug
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Severe Renal Impairment (Part I) | Number of Participants Who Discontinued Study Due to an AE | 0 participants |
| Healthy Participants (Part I) | Number of Participants Who Discontinued Study Due to an AE | 0 participants |
Primary
Number of Participants With an Adverse Event (AE)
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.
Time frame: From administration of study drug through 14 days after administration of study drug
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Severe Renal Impairment (Part I) | Number of Participants With an Adverse Event (AE) | 2 participants |
| Healthy Participants (Part I) | Number of Participants With an Adverse Event (AE) | 4 participants |