Trial Outcomes & Findings for Pharmacokinetics, Safety, and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Participants With Hepatic Impairment and in Healthy Participants (MK-8835-014) (NCT NCT02115347)
NCT ID: NCT02115347
Last Updated: 2018-08-20
Results Overview
Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (AUClast).
COMPLETED
PHASE1
16 participants
Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
2018-08-20
Participant Flow
Based on a statistical evaluation of the pharmacokinetic (PK) data obtained from participants with moderate hepatic impairment and matched healthy volunteers, and the pre-specified decision criteria, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
Participant milestones
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg - Mild Hepatic Impairment
Participants receive a single 15 mg oral dose (tablet) of ertugliflozin
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
0
|
|
Overall Study
COMPLETED
|
8
|
8
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics, Safety, and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Participants With Hepatic Impairment and in Healthy Participants (MK-8835-014)
Baseline characteristics by cohort
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.1 Years
FULL_RANGE 3.4 • n=5 Participants
|
55.5 Years
FULL_RANGE 3.0 • n=7 Participants
|
55.3 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hoursPopulation: The analysis population was all treated participants who had at least 1 measurement of the AUClast parameter. Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (AUClast).
Outcome measures
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin
|
1413 ng•hr/mL
Geometric Coefficient of Variation 39
|
1618 ng•hr/mL
Geometric Coefficient of Variation 14
|
PRIMARY outcome
Timeframe: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hoursPopulation: The analysis population was all treated participants who had at least 1 measurement of the AUCinf parameter. Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf).
Outcome measures
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
|---|---|---|
|
AUC From Hour 0 to Infinity (AUCinf) for Ertugliflozin
|
1430 ng•hr/mL
Geometric Coefficient of Variation 39
|
1636 ng•hr/mL
Geometric Coefficient of Variation 14
|
SECONDARY outcome
Timeframe: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hoursPopulation: The analysis population was all treated participants who had at least 1 measurement of the AUClast,u parameter. Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) for unbound drug (ertugliflozin only).
Outcome measures
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
|---|---|---|
|
AUClast for Fraction of Ertugliflozin Unbound in Plasma (AUClast,u)
|
52.47 ng•hr/mL
Geometric Coefficient of Variation 44
|
54.77 ng•hr/mL
Geometric Coefficient of Variation 15
|
SECONDARY outcome
Timeframe: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hoursPopulation: The analysis population was all treated participants who had at least 1 measurement of the AUCinf,u parameter. Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
Area under the plasma concentration-time profile from time zero extrapolated to infinite time for unbound drug (ertugliflozin only) (AUCinf, u).
Outcome measures
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
|---|---|---|
|
AUCinf for Fraction of Ertugliflozin Unbound in Plasma (AUCinf,u)
|
53.14 ng•hr/mL
Geometric Coefficient of Variation 44
|
55.40 ng•hr/mL
Geometric Coefficient of Variation 16
|
SECONDARY outcome
Timeframe: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hoursPopulation: The analysis population was all treated participants who had at least 1 measurement of the Cmax parameter. Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Outcome measures
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Ertugliflozin
|
251.1 ng/mL
Geometric Coefficient of Variation 27
|
319.0 ng/mL
Geometric Coefficient of Variation 11
|
SECONDARY outcome
Timeframe: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hoursPopulation: The analysis population was all treated participants who had at least 1 measurement of the Cmax,u parameter. Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
Maximum plasma concentration for unbound drug (ertugliflozin only).
Outcome measures
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
|---|---|---|
|
Cmax for Fraction of Ertugliflozin Unbound in Plasma (Cmax,u)
|
9.336 ng/mL
Geometric Coefficient of Variation 30
|
10.79 ng/mL
Geometric Coefficient of Variation 15
|
SECONDARY outcome
Timeframe: Up to 19 daysPopulation: The analysis population was defined as all treated participants. Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Outcome measures
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 Participants
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
|---|---|---|
|
Number of Participants Who Experienced an Adverse Event
|
2 Participants
|
3 Participants
|
Adverse Events
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
Ertugliflozin 15 mg (Normal Hepatic Function)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ertugliflozin 15 mg (Moderate Hepatic Impairment)
n=8 participants at risk
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
Ertugliflozin 15 mg (Normal Hepatic Function)
n=8 participants at risk
Participants received a single 15 mg oral dose (tablet) of ertugliflozin.
|
|---|---|---|
|
Cardiac disorders
Tachycardia
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Infections and infestations
Furuncle
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Nervous system disorders
Headache
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/8 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
12.5%
1/8 • Number of events 1 • Up to Day 19
Based on a statistical evaluation of the PK data from participants with moderate hepatic impairment and matched healthy volunteers, Part 2 of the study was not conducted and participants with mild hepatic impairment were not enrolled.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee Investigator will provide manuscripts, abstracts, or the full text of any other intended disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to the sponsor at least 30 days before they are submitted for publication or otherwise disclosed. If any patent action is required to protect intellectual property rights, Investigator agrees to delay the disclosure for a period not to exceed an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER