Chronic Renal Insufficiency, Type 2 Diabetes Mellitus
Conditions
Brief summary
This is a 2-part study in participants with renal impairment and matched healthy participants to investigate the effect of impaired renal function on the plasma and urine levels of omarigliptin (MK-3102) after taking a single 3 mg dose by mouth.
Detailed description
In Part I, three panels of 6 participants each will be enrolled with varying degrees of renal disease (mild, moderate, or severe renal impairment) based on their estimated glomerular filtration rate (eGFR). Each of these panels will be matched with a corresponding panel of equal number of healthy, age-, race-, BMI- and gender-matched control participants. All panels will receive a single oral dose of 3-mg omarigliptin, followed by plasma sampling and urine collection. In Part II, 6 participants with end stage renal disease (ESRD) requiring hemodialysis will receive a single 3-mg oral dose of omarigliptin immediately following hemodialysis (HD) (Period 1) and 2 hours prior to HD (Period 2).There will be approximately 1 month between Period 1 and Period 2. A corresponding panel of equal number, healthy matched control subjects (age, race, BMI, gender) will also receive a single 3 mg dose by mouth. Omarigliptin dose administration will be followed by plasma sampling for both panels.
Interventions
DRUGOmarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
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
Impaired Renal Function Subjects: * Females of reproductive potential must have a negative pregnancy test and agree to use 2 methods of birth control * Diagnosis of renal insufficiency based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation Healthy Subjects: * Females of reproductive potential must have a negative pregnancy test and agree to use 2 methods of birth control; * In general good health
Exclusion criteria
Impaired Renal Function Subjects: * Is mentally or legally incapacitated * Has rapidly fluctuating renal function or has demonstrated or suspected renal artery stenosis * History of significant endocrine (other than Type 2 diabetes), gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases * History of stroke, chronic seizures or major neurological disease * Uncontrolled Type 2 diabetes or history of Type 1 diabetes or ketoacidosis * History of cancer (Some exceptions apply) * Regular user of barbiturates or sleep aides * Consumes excessive amounts of alcohol (more than 2 drinks/day) * Consumes excessive amounts of caffeinated beverages (more than 6/day) * Has had major surgery or has lost or donated 1 unit of blood within 4 weeks * Has a history of significant multiple and/or severe allergies * Current or history of illicit drug abuse * Nursing mothers Healthy Subjects: * Is mentally or legally incapacitated; * Has a history of stroke, chronic seizures, or major neurological disorder * Renal impairment * History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases * Hypoglycemia, glucose intolerance, Type 1 or Type 2 diabetes, or ketoacidosis * History of cancer (Some exceptions apply) * Regular user of barbiturates or sleep aides * Consumes excessive amounts of alcohol (more than 2 drinks/day) * Consumes excessive amounts of caffeinated beverages (more than 6/day) * Has had major surgery or has lost or donated 1 unit of blood within 4 weeks * Has a history of significant multiple and/or severe allergies * Current or history of illicit drug abuse * Nursing mothers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose | AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose. |
| Maximum Concentration (Cmax) of Omarigliptin | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. |
| Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, and 168 hours post-dose | AUC0-168h is a measure of the total amount of drug in the plasma from the dose to 168 hours after the dose. |
| Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 168 hours post-dose | C168h is a measure of the plasma drug concentration 168 hours post-dose. |
| Apparent Volume of Distribution (Vd/F) of Omarigliptin | Up to 336 hours post-dose | Vd/F is defined as the distribution of a medication between the plasma and the rest of the body after the dose. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug. |
| Apparent Total Body Clearance (CL/F) of Omarigliptin | Up to 336 hours post-dose | CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic, and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). |
| Renal Clearance (CLr) of Omarigliptin | Up to 336 hours post-dose | CLr is a calculation of the rate at which a drug is removed from the body via renal clearance pathways, expressed as volume (milliliters) per unit of time (minutes). CLr was only determined for Panels A-F. |
| Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin | Up to 48 hours post-dose | fe48h is expressed as percentage of omarigliptin not metabolized and excreted in urine. fe48h was only determined for Panels A-F. |
| Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin | Up to 48 hours post-dose | Ae0-48h is a measure of the cumulative amount of drug excreted in the urine for 48 hours post-dose. Ae0-48h was only determined for Panels A-F. |
| Time to Maximum Concentration (Tmax) of Omarigliptin | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose | Tmax is a measure of the time to reach the maximum drug plasma concentration post-dose. |
| Apparent Terminal Half-life (t1/2) of Omarigliptin | Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose | T1/2 is the time required for the maximum concentration of a drug in the plasma to decrease by 50%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing an Adverse Event (AE) | From pre-dose to 14 days post-dose (Up to Day 15) | An AE was defined as any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Sponsor product, whether or not considered related to the use of the product. |
| Number of Participants Withdrawn From Study | Up to Day 15 | — |
Participant flow
Recruitment details
One healthy matched control participant withdrew consent for study participation on Day 15; this participant was replaced. Thus, a total of 49 participants were in the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Mild Renal Impairment (Panel A) Participants with estimated glomerular filtration rate (eGFR) ≥60 - \<80 mL/min/1.73 m² were enrolled in the Mild Renal Impairment group. | 6 |
| Part 1: Control to Match Panel A (Panel B) Participants with eGFR \>/= 80 mL/min/1.73 m² were matched by age, gender, race, and body mass index (BMI) to participants in Panel A. | 6 |
| Part 1: Moderate Renal Impairment (Panel C) Participants with eGFR ≥30 - \<60 mL/min/1.73 m² were enrolled in the Moderate Renal Impairment group. | 6 |
| Part 1: Control to Match Panel C (Panel D) Participants with eGFR \>/= 80 mL/min/1.73 m² were matched by age, gender, race, and body mass index (BMI) to participants in Panel C. | 6 |
| Part 1: Severe Renal Impairment (Panel E) Participants with eGFR \<30 mL/min/1.73 m² but not on dialysis were enrolled in the Severe Renal Impairment group. | 6 |
| Part 1: Control to Match Panel E (Panel F) Participants with eGFR \>/= 80 mL/min/1.73 m² were matched by age, gender, race, and body mass index (BMI) to participants in Panel E. | 6 |
| Part 2: ESRD Requiring HD (Panel G) Participants with end-stage renal disease (ESRD) requiring hemodialysis (HD) | 6 |
| Part 2: Control to Match Panel G (Panel H) Participants with eGFR \>/= 80 mL/min/1.73 m² were matched by age, gender, race, and body mass index (BMI) to participants in Panel G. | 7 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Severe Renal Impairment (Panel E) | Part 1: Control to Match Panel E (Panel F) | Part 1: Mild Renal Impairment (Panel A) | Part 1: Control to Match Panel A (Panel B) | Part 1: Moderate Renal Impairment (Panel C) | Part 1: Control to Match Panel C (Panel D) | Part 2: ESRD Requiring HD (Panel G) | Part 2: Control to Match Panel G (Panel H) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64 Years | 60 Years | 71 Years | 68 Years | 62 Years | 60 Years | 46 Years | 43 Years | 59 Years |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 21 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 28 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 6 | 4 / 6 | 1 / 6 | 1 / 6 | 1 / 6 | 0 / 6 | 1 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 |
Outcome results
Primary
Apparent Terminal Half-life (t1/2) of Omarigliptin
T1/2 is the time required for the maximum concentration of a drug in the plasma to decrease by 50%.
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Apparent Terminal Half-life (t1/2) of Omarigliptin | 148.3 hour | Standard Deviation 39 |
| Part 1: Control to Match Panel A (Panel B) | Apparent Terminal Half-life (t1/2) of Omarigliptin | 143.7 hour | Standard Deviation 21.9 |
| Part 1: Moderate Renal Impairment (Panel C) | Apparent Terminal Half-life (t1/2) of Omarigliptin | 156.2 hour | Standard Deviation 32 |
| Part 1: Control to Match Panel C (Panel D) | Apparent Terminal Half-life (t1/2) of Omarigliptin | 147.0 hour | Standard Deviation 65.4 |
| Part 1: Severe Renal Impairment (Panel E) | Apparent Terminal Half-life (t1/2) of Omarigliptin | 159.8 hour | Standard Deviation 55.7 |
| Part 1: Control to Match Panel E (Panel F) | Apparent Terminal Half-life (t1/2) of Omarigliptin | 155.0 hour | Standard Deviation 33.5 |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Apparent Terminal Half-life (t1/2) of Omarigliptin | 215.4 hour | Standard Deviation 38.7 |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Apparent Terminal Half-life (t1/2) of Omarigliptin | 162.6 hour | Standard Deviation 53.7 |
| Part 2: ESRD Requiring HD (Panel G) - Period 2 | Apparent Terminal Half-life (t1/2) of Omarigliptin | 263.7 hour | Standard Deviation 62.7 |
| Part 2: Control to Match Panel G (Panel H) - Period 2 | Apparent Terminal Half-life (t1/2) of Omarigliptin | 162.6 hour | Standard Deviation 53.7 |
Primary
Apparent Total Body Clearance (CL/F) of Omarigliptin
CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic, and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes).
Time frame: Up to 336 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Apparent Total Body Clearance (CL/F) of Omarigliptin | 26.51 mL/min |
| Part 1: Control to Match Panel A (Panel B) | Apparent Total Body Clearance (CL/F) of Omarigliptin | 25.02 mL/min |
| Part 1: Moderate Renal Impairment (Panel C) | Apparent Total Body Clearance (CL/F) of Omarigliptin | 21.55 mL/min |
| Part 1: Control to Match Panel C (Panel D) | Apparent Total Body Clearance (CL/F) of Omarigliptin | 28.91 mL/min |
| Part 1: Severe Renal Impairment (Panel E) | Apparent Total Body Clearance (CL/F) of Omarigliptin | 19.28 mL/min |
| Part 1: Control to Match Panel E (Panel F) | Apparent Total Body Clearance (CL/F) of Omarigliptin | 30.09 mL/min |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Apparent Total Body Clearance (CL/F) of Omarigliptin | 17.18 mL/min |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Apparent Total Body Clearance (CL/F) of Omarigliptin | 32.44 mL/min |
| Part 2: ESRD Requiring HD (Panel G) - Period 2 | Apparent Total Body Clearance (CL/F) of Omarigliptin | 16.43 mL/min |
| Part 2: Control to Match Panel G (Panel H) - Period 2 | Apparent Total Body Clearance (CL/F) of Omarigliptin | 32.44 mL/min |
90% CI: [0.9, 1.25]GMR of Panel A:Panel B
90% CI: [0.62, 0.89]GMR of Panel C:Panel D
90% CI: [0.54, 0.76]GMR of Panel E:Panel F
90% CI: [0.39, 0.71]GMR of Panel G:Panel H
90% CI: [0.38, 0.68]GMR of Panel G:Panel H
Primary
Apparent Volume of Distribution (Vd/F) of Omarigliptin
Vd/F is defined as the distribution of a medication between the plasma and the rest of the body after the dose. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug.
Time frame: Up to 336 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 349.42 L |
| Part 1: Control to Match Panel A (Panel B) | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 314.39 L |
| Part 1: Moderate Renal Impairment (Panel C) | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 295.86 L |
| Part 1: Control to Match Panel C (Panel D) | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 392.75 L |
| Part 1: Severe Renal Impairment (Panel E) | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 280.58 L |
| Part 1: Control to Match Panel E (Panel F) | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 410.21 L |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 334.57 L |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 478.52 L |
| Part 2: ESRD Requiring HD (Panel G) - Period 2 | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 383.12 L |
| Part 2: Control to Match Panel G (Panel H) - Period 2 | Apparent Volume of Distribution (Vd/F) of Omarigliptin | 478.52 L |
90% CI: [0.87, 1.42]GMR of Panel A:Panel B
90% CI: [0.53, 1.07]GMR of Panel C:Panel D
90% CI: [0.51, 0.92]GMR of Panel E:Panel F
90% CI: [0.5, 0.98]GMR of Panel G:Panel H
90% CI: [0.57, 1.12]GMR of Panel G:Panel H
Primary
Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin
AUC0-168h is a measure of the total amount of drug in the plasma from the dose to 168 hours after the dose.
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, and 168 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 3055.48 nM*hr |
| Part 1: Control to Match Panel A (Panel B) | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 3315.01 nM*hr |
| Part 1: Moderate Renal Impairment (Panel C) | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 3674.50 nM*hr |
| Part 1: Control to Match Panel C (Panel D) | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 2770.54 nM*hr |
| Part 1: Severe Renal Impairment (Panel E) | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 3580.02 nM*hr |
| Part 1: Control to Match Panel E (Panel F) | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 2615.56 nM*hr |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 3352.27 nM*hr |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 2431.77 nM*hr |
| Part 2: ESRD Requiring HD (Panel G) - Period 2 | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 3150.93 nM*hr |
| Part 2: Control to Match Panel G (Panel H) - Period 2 | Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin | 2431.77 nM*hr |
90% CI: [0.81, 1.05]GMR of Panel A:Panel B
90% CI: [1.07, 1.65]GMR of Panel C:Panel D
90% CI: [1.13, 1.65]GMR of Panel E:Panel F
90% CI: [1.06, 1.79]GMR of Panel G:Panel H
90% CI: [1, 1.68]GMR of Panel G:Panel H
Primary
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin
AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 4703.16 nM*hr |
| Part 1: Control to Match Panel A (Panel B) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 4983.58 nM*hr |
| Part 1: Moderate Renal Impairment (Panel C) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 5785.21 nM*hr |
| Part 1: Control to Match Panel C (Panel D) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 4312.17 nM*hr |
| Part 1: Severe Renal Impairment (Panel E) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 6466.65 nM*hr |
| Part 1: Control to Match Panel E (Panel F) | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 4142.94 nM*hr |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 7257.17 nM*hr |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 3842.62 nM*hr |
| Part 2: ESRD Requiring HD (Panel G) - Period 2 | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 7585.94 nM*hr |
| Part 2: Control to Match Panel G (Panel H) - Period 2 | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin | 3842.62 nM*hr |
90% CI: [0.8, 1.11]Geometric mean ratio (GMR)
90% CI: [1.12, 1.61]GMR of Panel C:Panel D
90% CI: [1.32, 1.85]GMR of Panel E:Panel F
90% CI: [1.4, 2.55]GMR of Panel G:Panel H
90% CI: [1.46, 2.66]GMR of Panel G:Panel H
Primary
Concentration at 168 Hours Post-dose (C168h) of Omarigliptin
C168h is a measure of the plasma drug concentration 168 hours post-dose.
Time frame: 168 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 7.19 nM |
| Part 1: Control to Match Panel A (Panel B) | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 7.85 nM |
| Part 1: Moderate Renal Impairment (Panel C) | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 9.10 nM |
| Part 1: Control to Match Panel C (Panel D) | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 6.28 nM |
| Part 1: Severe Renal Impairment (Panel E) | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 11.48 nM |
| Part 1: Control to Match Panel E (Panel F) | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 6.28 nM |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 11.46 nM |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 6.05 nM |
| Part 2: ESRD Requiring HD (Panel G) - Period 2 | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 11.35 nM |
| Part 2: Control to Match Panel G (Panel H) - Period 2 | Concentration at 168 Hours Post-dose (C168h) of Omarigliptin | 6.05 nM |
90% CI: [0.75, 1.12]GMR of Panel A:Panel B
90% CI: [1.19, 1.76]GMR of Panel C:Panel D
90% CI: [1.49, 2.24]GMR of Panel E:Panel F
90% CI: [1.41, 2.54]GMR of Panel G:Panel H
90% CI: [1.4, 2.52]GMR of Panel G:Panel H
Primary
Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin
Ae0-48h is a measure of the cumulative amount of drug excreted in the urine for 48 hours post-dose. Ae0-48h was only determined for Panels A-F.
Time frame: Up to 48 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin | 1.04 mg |
| Part 1: Control to Match Panel A (Panel B) | Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin | 1.21 mg |
| Part 1: Moderate Renal Impairment (Panel C) | Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin | 0.79 mg |
| Part 1: Control to Match Panel C (Panel D) | Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin | 0.88 mg |
| Part 1: Severe Renal Impairment (Panel E) | Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin | 0.45 mg |
| Part 1: Control to Match Panel E (Panel F) | Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin | 0.90 mg |
90% CI: [0.69, 1.07]GMR of Panel A:Panel B
90% CI: [0.7, 1.15]GMR of Panel C:Panel D
90% CI: [0.37, 0.67]GMR of Panel E:Panel F
Primary
Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin
fe48h is expressed as percentage of omarigliptin not metabolized and excreted in urine. fe48h was only determined for Panels A-F.
Time frame: Up to 48 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin | 35 Percentage of total dose |
| Part 1: Control to Match Panel A (Panel B) | Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin | 41 Percentage of total dose |
| Part 1: Moderate Renal Impairment (Panel C) | Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin | 27 Percentage of total dose |
| Part 1: Control to Match Panel C (Panel D) | Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin | 30 Percentage of total dose |
| Part 1: Severe Renal Impairment (Panel E) | Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin | 15 Percentage of total dose |
| Part 1: Control to Match Panel E (Panel F) | Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin | 31 Percentage of total dose |
90% CI: [0.69, 1.07]GMR of Panel A:Panel B
90% CI: [0.7, 1.15]GMR of Panel C:Panel D
90% CI: [0.37, 0.67]GMR of Panel E:Panel F
Primary
Maximum Concentration (Cmax) of Omarigliptin
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Maximum Concentration (Cmax) of Omarigliptin | 60.37 nM | 95% Confidence Interval 51.82 |
| Part 1: Control to Match Panel A (Panel B) | Maximum Concentration (Cmax) of Omarigliptin | 64.03 nM | — |
| Part 1: Moderate Renal Impairment (Panel C) | Maximum Concentration (Cmax) of Omarigliptin | 61.43 nM | — |
| Part 1: Control to Match Panel C (Panel D) | Maximum Concentration (Cmax) of Omarigliptin | 54.34 nM | — |
| Part 1: Severe Renal Impairment (Panel E) | Maximum Concentration (Cmax) of Omarigliptin | 48.65 nM | — |
| Part 1: Control to Match Panel E (Panel F) | Maximum Concentration (Cmax) of Omarigliptin | 53.89 nM | — |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Maximum Concentration (Cmax) of Omarigliptin | 41.43 nM | — |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Maximum Concentration (Cmax) of Omarigliptin | 56.06 nM | — |
| Part 2: ESRD Requiring HD (Panel G) - Period 2 | Maximum Concentration (Cmax) of Omarigliptin | 40.98 nM | — |
| Part 2: Control to Match Panel G (Panel H) - Period 2 | Maximum Concentration (Cmax) of Omarigliptin | 56.06 nM | — |
90% CI: [0.79, 1.12]GMR of Panel A:Panel B
90% CI: [0.91, 1.41]GMR of Panel C:Panel D
90% CI: [0.66, 1.23]GMR of Panel E:Panel F
90% CI: [0.57, 0.96]GMR of Panel E:Panel F
90% CI: [0.56, 0.95]GMR of Panel E:Panel F
Primary
Renal Clearance (CLr) of Omarigliptin
CLr is a calculation of the rate at which a drug is removed from the body via renal clearance pathways, expressed as volume (milliliters) per unit of time (minutes). CLr was only determined for Panels A-F.
Time frame: Up to 336 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Renal Clearance (CLr) of Omarigliptin | 27.26 mL/min |
| Part 1: Control to Match Panel A (Panel B) | Renal Clearance (CLr) of Omarigliptin | 29.27 mL/min |
| Part 1: Moderate Renal Impairment (Panel C) | Renal Clearance (CLr) of Omarigliptin | 17.93 mL/min |
| Part 1: Control to Match Panel C (Panel D) | Renal Clearance (CLr) of Omarigliptin | 24.71 mL/min |
| Part 1: Severe Renal Impairment (Panel E) | Renal Clearance (CLr) of Omarigliptin | 12.18 mL/min |
| Part 1: Control to Match Panel E (Panel F) | Renal Clearance (CLr) of Omarigliptin | 28.84 mL/min |
90% CI: [0.74, 1.18]GMR of Panel A:Panel B
90% CI: [0.55, 0.96]GMR of Panel C:Panel D
90% CI: [0.33, 0.54]GMR of Panel E:Panel F
Primary
Time to Maximum Concentration (Tmax) of Omarigliptin
Tmax is a measure of the time to reach the maximum drug plasma concentration post-dose.
Time frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Time to Maximum Concentration (Tmax) of Omarigliptin | 3.0 hour |
| Part 1: Control to Match Panel A (Panel B) | Time to Maximum Concentration (Tmax) of Omarigliptin | 1.5 hour |
| Part 1: Moderate Renal Impairment (Panel C) | Time to Maximum Concentration (Tmax) of Omarigliptin | 2.0 hour |
| Part 1: Control to Match Panel C (Panel D) | Time to Maximum Concentration (Tmax) of Omarigliptin | 1.5 hour |
| Part 1: Severe Renal Impairment (Panel E) | Time to Maximum Concentration (Tmax) of Omarigliptin | 2.0 hour |
| Part 1: Control to Match Panel E (Panel F) | Time to Maximum Concentration (Tmax) of Omarigliptin | 1.5 hour |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Time to Maximum Concentration (Tmax) of Omarigliptin | 4.0 hour |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Time to Maximum Concentration (Tmax) of Omarigliptin | 1.0 hour |
| Part 2: ESRD Requiring HD (Panel G) - Period 2 | Time to Maximum Concentration (Tmax) of Omarigliptin | 4.0 hour |
| Part 2: Control to Match Panel G (Panel H) - Period 2 | Time to Maximum Concentration (Tmax) of Omarigliptin | 1.0 hour |
Secondary
Number of Participants Experiencing an Adverse Event (AE)
An AE was defined as any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Sponsor product, whether or not considered related to the use of the product.
Time frame: From pre-dose to 14 days post-dose (Up to Day 15)
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Number of Participants Experiencing an Adverse Event (AE) | 1 Participants |
| Part 1: Control to Match Panel A (Panel B) | Number of Participants Experiencing an Adverse Event (AE) | 1 Participants |
| Part 1: Moderate Renal Impairment (Panel C) | Number of Participants Experiencing an Adverse Event (AE) | 4 Participants |
| Part 1: Control to Match Panel C (Panel D) | Number of Participants Experiencing an Adverse Event (AE) | 1 Participants |
| Part 1: Severe Renal Impairment (Panel E) | Number of Participants Experiencing an Adverse Event (AE) | 1 Participants |
| Part 1: Control to Match Panel E (Panel F) | Number of Participants Experiencing an Adverse Event (AE) | 1 Participants |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Number of Participants Experiencing an Adverse Event (AE) | 0 Participants |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Number of Participants Experiencing an Adverse Event (AE) | 1 Participants |
Secondary
Number of Participants Withdrawn From Study
Time frame: Up to Day 15
Population: All participants that received a single 3 mg dose of omarigliptin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Mild Renal Impairment (Panel A) | Number of Participants Withdrawn From Study | 0 Participants |
| Part 1: Control to Match Panel A (Panel B) | Number of Participants Withdrawn From Study | 0 Participants |
| Part 1: Moderate Renal Impairment (Panel C) | Number of Participants Withdrawn From Study | 0 Participants |
| Part 1: Control to Match Panel C (Panel D) | Number of Participants Withdrawn From Study | 0 Participants |
| Part 1: Severe Renal Impairment (Panel E) | Number of Participants Withdrawn From Study | 0 Participants |
| Part 1: Control to Match Panel E (Panel F) | Number of Participants Withdrawn From Study | 0 Participants |
| Part 2: ESRD Requiring HD (Panel G) - Period 1 | Number of Participants Withdrawn From Study | 0 Participants |
| Part 2: Control to Match Panel G (Panel H) - Period 1 | Number of Participants Withdrawn From Study | 0 Participants |