Diabetes Mellitus, Type 2
Conditions
Keywords
Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases
Brief summary
This study will investigate and compare the pharmacokinetics of a single 25-mg dose of MK-3102 in participants with moderate hepatic impairment and matched healthy participants. The primary hypothesis is that in participants with moderately impaired hepatic function, the area under the concentration-time curve from time zero to infinity (AUC0-∞) is similar to that observed in healthy matched control participants following a single 25 mg oral dose of MK-3102. Specifically, the true ratio (moderately impaired hepatic function patients/healthy matched control subjects) of geometric means for AUC0-∞ is no greater than 2.
Interventions
DRUGMK-3102
Single dose of 25 mg of MK-3102 (1 x 25 mg capsule) administered orally on Day 1.
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 80 Years
Healthy volunteers
Yes
Inclusion criteria
Impaired Hepatic Function Participants: * A diagnosis of: 1. Chronic (\> 6 months) hepatic insufficiency 2. Stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology * Score on the Child-Pugh Scale of 7 to 9 (moderate hepatic insufficiency) * Estimated creatinine clearance (CLCr) \> 60 mL/min or glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 Both Impaired Hepatic Function and Healthy Participants: * In general good health * Continuous non-smokers or moderate smokers for at least 3 months prior to study start * Body Mass Index ≤39 kg/m\^2 * Females of reproductive potential must have a negative pregnancy test and agree to use acceptable birth control method(s) or remain sexually inactive throughout study * Non-vasectomized male patients must agree to use acceptable birth control method(s) or abstain from sexual intercourse during the trial and for 3 months after the study
Exclusion criteria
Healthy Participants: * History or presence of alcoholism within the past 2 years * Presence of hepatitis B virus (HBV) or hepatitis virus C (HVC) Both Impaired Hepatic Function and Healthy Participants: * History or presence of drug abuse within the past 2 years * History or presence of human immunodeficiency virus (HIV) * History or presence of significant cardiovascular, pulmonary, renal, hematologic, gastrointestinal (other than hepatic impairment), endocrine, immunologic, dermatologic, or neurological disease * Use of any medication or substance (including prescription or over the counter, health supplements, natural or herbal supplements) which cannot be discontinued at least 14 days prior to the study start and throughout the study * Has been on a special diet within 28 days prior to the study start * Blood donation within 56 days or plasma donation within 7 days prior to study start * Participation in another clinical trial within 28 days of study start * Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) From Hour 0 to Infinity (AUC0-∞) | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration at 168 Hours After Dosing (C168h) | 168 hours post-dose | — |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose | — |
| Time to Maximum Observed Plasma Drug Concentration (Tmax) | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose | — |
| Area Under the Concentration Versus Time Curve From Hour 0 to 168 Hours After Dosing (AUC0-168h) | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose | — |
| Number of Participants Experiencing Adverse Events (AEs) | Up to 14 days post-dose | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient/subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants Discontinued From Study Due to AEs | Up to 14 days post-dose | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient/subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Apparent Terminal Phase Half-life (t½) | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose | — |
Participant flow
Recruitment details
Adult (18 to 80 years of age) males and females participated in the study. Eight participants with moderate hepatic impairment, and eight healthy control participants (matched according to age, weight, gender, and creatinine clearance \[CLCr\] or estimated glomerular filtration rate \[eGFR\]), were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Moderate Hepatic Impairment Group Participants with Child-Pugh scores of 7-9 were enrolled in the Moderate Hepatic Impairment group. | 8 |
| Healthy Matched Control Group Healthy participants matched according to mean age (±15 years), mean weight (±10 kg), and mean CLCr (±20 mL/min) or mean eGFR (±20 mL/min/1.73 m²) to same-gender participants with moderate hepatic impairment were enrolled in the Control group. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Moderate Hepatic Impairment Group | Healthy Matched Control Group | Total |
|---|---|---|---|
| Age, Continuous | 57 Years FULL_RANGE 6.45 | 53 Years FULL_RANGE 8.45 | 55 Years FULL_RANGE 7.55 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 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 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) From Hour 0 to Infinity (AUC0-∞)
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose
Population: All participants that received omarigliptin 25 mg.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate Hepatic Impairment Group | Area Under the Plasma Concentration Versus Time Curve (AUC) From Hour 0 to Infinity (AUC0-∞) | 23.3 µM*hr |
| Healthy Matched Control Group | Area Under the Plasma Concentration Versus Time Curve (AUC) From Hour 0 to Infinity (AUC0-∞) | 24.9 µM*hr |
95% CI: [0.79, 1.11]Geometric least-squares mean ratio (GMR)
Secondary
Apparent Terminal Phase Half-life (t½)
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose
Population: All participants that received omarigliptin 25 mg.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate Hepatic Impairment Group | Apparent Terminal Phase Half-life (t½) | 34.6 hr | Geometric Coefficient of Variation 17.4 |
| Healthy Matched Control Group | Apparent Terminal Phase Half-life (t½) | 34.5 hr | Geometric Coefficient of Variation 13.4 |
Secondary
Area Under the Concentration Versus Time Curve From Hour 0 to 168 Hours After Dosing (AUC0-168h)
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose
Population: All participants that received omarigliptin 25 mg.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate Hepatic Impairment Group | Area Under the Concentration Versus Time Curve From Hour 0 to 168 Hours After Dosing (AUC0-168h) | 22.4 µM*hr |
| Healthy Matched Control Group | Area Under the Concentration Versus Time Curve From Hour 0 to 168 Hours After Dosing (AUC0-168h) | 23.8 µM*hr |
95% CI: [0.81, 1.1]Geometric least-squares mean ratio (GMR)
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose
Population: All participants that received omarigliptin 25 mg.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate Hepatic Impairment Group | Maximum Observed Plasma Concentration (Cmax) | 572 nM |
| Healthy Matched Control Group | Maximum Observed Plasma Concentration (Cmax) | 554 nM |
95% CI: [0.93, 1.15]Geometric least-squares mean ratio (GMR)
Secondary
Number of Participants Discontinued From Study Due to AEs
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient/subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 14 days post-dose
Population: All participants that received omarigliptin 25 mg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moderate Hepatic Impairment Group | Number of Participants Discontinued From Study Due to AEs | 0 Participants |
| Healthy Matched Control Group | Number of Participants Discontinued From Study Due to AEs | 0 Participants |
Secondary
Number of Participants Experiencing Adverse Events (AEs)
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient/subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 14 days post-dose
Population: All participants that received omarigliptin 25 mg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Moderate Hepatic Impairment Group | Number of Participants Experiencing Adverse Events (AEs) | 2 Participants |
| Healthy Matched Control Group | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
Secondary
Plasma Concentration at 168 Hours After Dosing (C168h)
Time frame: 168 hours post-dose
Population: All participants that received omarigliptin 25 mg.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate Hepatic Impairment Group | Plasma Concentration at 168 Hours After Dosing (C168h) | 15.7 nM |
| Healthy Matched Control Group | Plasma Concentration at 168 Hours After Dosing (C168h) | 19.4 nM |
95% CI: [0.51, 1.28]Geometric least-squares mean ratio (GMR)
Secondary
Time to Maximum Observed Plasma Drug Concentration (Tmax)
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose
Population: All participants that received omarigliptin 25 mg.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate Hepatic Impairment Group | Time to Maximum Observed Plasma Drug Concentration (Tmax) | 2 hr |
| Healthy Matched Control Group | Time to Maximum Observed Plasma Drug Concentration (Tmax) | 2 hr |