Trial Outcomes & Findings for A Study of Tirzepatide in Participants With Impaired Liver Function (NCT NCT03940742)
NCT ID: NCT03940742
Last Updated: 2023-03-24
Results Overview
Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC\[0-∞\]) of Tirzepatide.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dose
Results posted on
2023-03-24
Participant Flow
Participant milestones
| Measure |
Control (Normal Hepatic Function)
Participants with normal hepatic function received single subcutaneous dose of 5 mg tirzepatide.
|
Mild Hepatic Impairment
Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Moderate Hepatic Impairment
Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
13
|
6
|
6
|
7
|
|
Overall Study
Received at Least One Dose of Study Drug
|
13
|
6
|
6
|
7
|
|
Overall Study
COMPLETED
|
13
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Control (Normal Hepatic Function)
Participants with normal hepatic function received single subcutaneous dose of 5 mg tirzepatide.
|
Mild Hepatic Impairment
Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Moderate Hepatic Impairment
Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Severe Hepatic Impairment
Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Study of Tirzepatide in Participants With Impaired Liver Function
Baseline characteristics by cohort
| Measure |
Control (Normal Hepatic Function)
n=13 Participants
Participants with normal hepatic function received single subcutaneous dose of 5 mg tirzepatide.
|
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Moderate Hepatic Impairment
n=6 Participants
Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Severe Hepatic Impairment
n=7 Participants
Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Continuous
|
55.8 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
63.2 years
STANDARD_DEVIATION 4.5 • n=7 Participants
|
51.3 years
STANDARD_DEVIATION 15.4 • n=5 Participants
|
60.4 years
STANDARD_DEVIATION 6.6 • n=4 Participants
|
57.4 years
STANDARD_DEVIATION 10.8 • n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
13 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
32 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dosePopulation: All participants who received at least one dose of study drug and had evaluable PK data.
Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC\[0-∞\]) of Tirzepatide.
Outcome measures
| Measure |
Control (Normal Hepatic Function)
n=13 Participants
Participants with normal hepatic function received single subcutaneous dose of 5 mg tirzepatide.
|
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Moderate Hepatic Impairment
n=6 Participants
Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Severe Hepatic Impairment
n=6 Participants
Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC[0-∞]) of Tirzepatide
|
84300 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 28
|
102000 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 16
|
82000 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 29
|
77000 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 33
|
PRIMARY outcome
Timeframe: Predose, 8, 12, 24, 48, 72, 96, 168 and 336 post dosePopulation: All participants who received at least one dose of study drug and had evaluable PK data.
PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide.
Outcome measures
| Measure |
Control (Normal Hepatic Function)
n=13 Participants
Participants with normal hepatic function received single subcutaneous dose of 5 mg tirzepatide.
|
Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Moderate Hepatic Impairment
n=6 Participants
Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Severe Hepatic Impairment
n=7 Participants
Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
|---|---|---|---|---|
|
PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide
|
510 ng/mL
Geometric Coefficient of Variation 28
|
509 ng/mL
Geometric Coefficient of Variation 18
|
516 ng/mL
Geometric Coefficient of Variation 44
|
521 ng/mL
Geometric Coefficient of Variation 23
|
Adverse Events
Control (Normal Hepatic Function)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Mild Hepatic Impairment
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Severe Hepatic Impairment
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Control (Normal Hepatic Function)
n=13 participants at risk
Participants with normal hepatic function received single subcutaneous dose of 5 mg tirzepatide.
|
Mild Hepatic Impairment
n=6 participants at risk
Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Moderate Hepatic Impairment
n=6 participants at risk
Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Severe Hepatic Impairment
n=7 participants at risk
Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
|---|---|---|---|---|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
14.3%
1/7 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
Other adverse events
| Measure |
Control (Normal Hepatic Function)
n=13 participants at risk
Participants with normal hepatic function received single subcutaneous dose of 5 mg tirzepatide.
|
Mild Hepatic Impairment
n=6 participants at risk
Participants with mild hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Moderate Hepatic Impairment
n=6 participants at risk
Participants with moderate hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
Severe Hepatic Impairment
n=7 participants at risk
Participants with severe hepatic impairment received single subcutaneous dose of 5 mg tirzepatide.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
14.3%
1/7 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
16.7%
1/6 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/7 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
15.4%
2/13 • Number of events 2 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/7 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
14.3%
1/7 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
16.7%
1/6 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/7 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
16.7%
1/6 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/7 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
23.1%
3/13 • Number of events 3 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
33.3%
2/6 • Number of events 2 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
14.3%
1/7 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
16.7%
1/6 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
33.3%
2/6 • Number of events 2 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
14.3%
1/7 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
General disorders
Influenza like illness
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
16.7%
1/6 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/7 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
14.3%
1/7 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
16.7%
1/6 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
14.3%
1/7 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/13 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
16.7%
1/6 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/7 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
7.7%
1/13 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/7 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
7.7%
1/13 • Number of events 1 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/6 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
0.00%
0/7 • Baseline to Study Completion (Up to 14 Months)
All participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60