Trial Outcomes & Findings for Impact of Metformin and Polysorbate 80 on Drug Absorption and Disposition (NCT NCT04640571)
NCT ID: NCT04640571
Last Updated: 2024-07-16
Results Overview
Pravastatin AUC after metformin, compared to pravastatin AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
18 participants
Primary outcome timeframe
0-10 hours
Results posted on
2024-07-16
Participant Flow
UMB IRB, a subject is enrolled if they signed a consent form, regardless if they passed screening.
Participant milestones
| Measure |
Placebo, Then Metformin, Then Polysorbate 80
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Metformin, Then Polysorbate 80, Then Placebo
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Polysorbate 80, Then Placebo, Then Metformin
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Polysorbate 80, Then Metformin, Then Placebo
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Placebo, Then Polysorbate 80, Then Metformin
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Metformin, Then Placebo, Then Polysorbate 80
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
2
|
2
|
2
|
2
|
2
|
4
|
|
Overall Study
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
2
|
Reasons for withdrawal
| Measure |
Placebo, Then Metformin, Then Polysorbate 80
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Metformin, Then Polysorbate 80, Then Placebo
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Polysorbate 80, Then Placebo, Then Metformin
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Polysorbate 80, Then Metformin, Then Placebo
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Placebo, Then Polysorbate 80, Then Metformin
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Metformin, Then Placebo, Then Polysorbate 80
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
2
|
Baseline Characteristics
Impact of Metformin and Polysorbate 80 on Drug Absorption and Disposition
Baseline characteristics by cohort
| Measure |
Placebo, Then Metformin, Then Polysorbate 80
n=2 Participants
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Metformin, Then Polysorbate 80, Then Placebo
n=2 Participants
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Polysorbate 80, Then Placebo, Then Metformin
n=2 Participants
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Polysorbate 80, Then Metformin, Then Placebo
n=2 Participants
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Placebo, Then Polysorbate 80, Then Metformin
n=2 Participants
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Metformin, Then Placebo, Then Polysorbate 80
n=2 Participants
Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
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
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
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
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Continuous
|
28.5 years
n=5 Participants
|
26.5 years
n=7 Participants
|
28.5 years
n=5 Participants
|
26.5 years
n=4 Participants
|
40 years
n=21 Participants
|
28 years
n=8 Participants
|
29.7 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White/Caucasian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
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
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
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
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 0-10 hoursPravastatin AUC after metformin, compared to pravastatin AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Area-Under-the-Curve (AUC) of Pravastatin After Metformin
|
264.2 ng/ml × h
Standard Error 34.1
|
170.5 ng/ml × h
Standard Error 24.7
|
PRIMARY outcome
Timeframe: 0-10 hoursPravastatin Cmax after metformin, compared to pravastatin Cmax after placebo. Cmax units are concentration (i.e. ng/ml).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) of Pravastatin After Metformin
|
119.3 ng/ml
Standard Error 17.7
|
86.43 ng/ml
Standard Error 15.86
|
PRIMARY outcome
Timeframe: 0-10 hoursBaseline-corrected chenodeoxycholic acid AUC after metformin. AUC Units are concentration x time (i.e. ng/ml x h). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid After Metformin
|
4646 ng/ml x h
Standard Error 352
|
4665 ng/ml x h
Standard Error 370
|
PRIMARY outcome
Timeframe: 0-10 hoursBaseline-corrected chenodeoxycholic acid Cmax after metformin. Cmax units are concentration (i.e. ng/ml). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid After Metformin
|
2695 ng/ml
Standard Error 453
|
2881 ng/ml
Standard Error 351
|
PRIMARY outcome
Timeframe: 0-10 hoursAcyclovir AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Area-Under-the-Curve (AUC) of Acyclovir After Polysorbate 80
|
10039 ng/ml x h
Standard Error 903
|
9839 ng/ml x h
Standard Error 782
|
PRIMARY outcome
Timeframe: 0-10 hoursAcyclovir Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) of Acyclovir After Polysorbate 80
|
3363 ng/ml
Standard Error 348
|
3230 ng/ml
Standard Error 367
|
PRIMARY outcome
Timeframe: 0-10 hoursBaseline-corrected Chenodeoxycholic acid AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80
|
4964 ng/ml x h
Standard Error 300
|
4665 ng/ml x h
Standard Error 370
|
PRIMARY outcome
Timeframe: 0-10 hoursBaseline-corrected Chenodeoxycholic acid Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80
|
2960 ng/ml
Standard Error 276
|
2881 ng/ml
Standard Error 351
|
PRIMARY outcome
Timeframe: 0-10 hoursEnalaprilat AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Area-Under-the-Curve (AUC) of Enalaprilat After Polysorbate 80
|
10.98 ng/ml x h
Standard Error 3.05
|
12.10 ng/ml x h
Standard Error 2.71
|
PRIMARY outcome
Timeframe: 0-10 hoursEnalaprilat Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) of Enalaprilat After Polysorbate 80
|
1.720 ng/ml
Standard Error 0.480
|
2.080 ng/ml
Standard Error 0.540
|
SECONDARY outcome
Timeframe: 0-10 hoursFor each of 15 endogenous bile acid, endogenous bile acid AUC after polysorbate 80, compared to endogenous bile acid AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Lithocholic acid
|
74.02 ng/ml x h
Standard Error 13.14
|
67.64 ng/ml x h
Standard Error 14.64
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Glycolithocholic acid
|
165.3 ng/ml x h
Standard Error 32.3
|
192.1 ng/ml x h
Standard Error 57.8
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Taurolithocholic acid
|
21.66 ng/ml x h
Standard Error 3.04
|
21.02 ng/ml x h
Standard Error 4.55
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Cholic acid
|
264.3 ng/ml x h
Standard Error 50.6
|
259.7 ng/ml x h
Standard Error 64.6
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Glycocholic acid
|
1171 ng/ml x h
Standard Error 185
|
1053 ng/ml x h
Standard Error 187
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Taurocholic acid
|
280.8 ng/ml x h
Standard Error 40.9
|
248.1 ng/ml x h
Standard Error 39.5
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Deoxycholic acid
|
1451 ng/ml x h
Standard Error 242
|
1222 ng/ml x h
Standard Error 158
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Glycodeoxycholic acid
|
1655 ng/ml x h
Standard Error 183
|
1507 ng/ml x h
Standard Error 200
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Taurodeoxycholic acid
|
346.7 ng/ml x h
Standard Error 38.6
|
329.3 ng/ml x h
Standard Error 53.1
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Chenodeoxycholic acid
|
5718 ng/ml x h
Standard Error 409
|
5552 ng/ml x h
Standard Error 471
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Glycochenodeoxycholic acid
|
7172 ng/ml x h
Standard Error 852
|
7386 ng/ml x h
Standard Error 847
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Taurochenodeoxycholic acid
|
1467 ng/ml x h
Standard Error 204
|
1393 ng/ml x h
Standard Error 195
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Ursodeoxycholic acid
|
116.5 ng/ml x h
Standard Error 24.3
|
243.7 ng/ml x h
Standard Error 159.7
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Glycoursodeoxycholic acid
|
415.5 ng/ml x h
Standard Error 57.4
|
542.1 ng/ml x h
Standard Error 181.9
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
Tauroursodeoxycholic acid
|
19.79 ng/ml x h
Standard Error 3.81
|
17.07 ng/ml x h
Standard Error 3.33
|
SECONDARY outcome
Timeframe: 0-10 hoursFor each of 15 endogenous bile acid, endogenous bile acid Cmax after metformin, compared to endogenous bile acid Cmax after placebo. Cmax units are concentration (i.e. ng/ml).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Taurodeoxycholic acid
|
49.66 ng/ml
Standard Error 8.07
|
86.14 ng/ml
Standard Error 16.50
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Chenodeoxycholic acid
|
2782 ng/ml
Standard Error 451
|
2982 ng/ml
Standard Error 359
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Taurolithocholic acid
|
4.020 ng/ml
Standard Error 0.610
|
6.150 ng/ml
Standard Error 1.800
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Ursodeoxycholic acid
|
65.54 ng/ml
Standard Error 39.40
|
41.60 ng/ml
Standard Error 24.98
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Glycoursodeoxycholic acid
|
121.5 ng/ml
Standard Error 42.6
|
118.0 ng/ml
Standard Error 38.3
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Tauroursodeoxycholic acid
|
3.350 ng/ml
Standard Error 0.420
|
5.010 ng/ml
Standard Error 0.930
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Cholic acid
|
109.6 ng/ml
Standard Error 40.5
|
123.8 ng/ml
Standard Error 51.0
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Glycocholic acid
|
149.8 ng/ml
Standard Error 37.5
|
263.9 ng/ml
Standard Error 44.8
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Taurocholic acid
|
28.58 ng/ml
Standard Error 6.20
|
67.64 ng/ml
Standard Error 12.96
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Deoxycholic acid
|
234.0 ng/ml
Standard Error 44.9
|
199.7 ng/ml
Standard Error 28.6
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Glycodeoxycholic acid
|
338.1 ng/ml
Standard Error 61.1
|
375.7 ng/ml
Standard Error 50.9
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Glycochenodeoxycholic acid
|
1338 ng/ml
Standard Error 267
|
1667 ng/ml
Standard Error 234
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Taurochenodeoxycholic acid
|
192.9 ng/ml
Standard Error 32.9
|
349.8 ng/ml
Standard Error 69.7
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Lithocholic acid
|
10.88 ng/ml
Standard Error 1.62
|
9.400 ng/ml
Standard Error 2.040
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
Glycolithocholic acid
|
36.20 ng/ml
Standard Error 6.84
|
43.31 ng/ml
Standard Error 12.76
|
SECONDARY outcome
Timeframe: 0-10 hoursFor each of 15 endogenous bile acid, endogenous bile acid AUC after metformin, compared to endogenous bile acid AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Glycocholic acid
|
678.5 ng/ml x h
Standard Error 131.4
|
1053 ng/ml x h
Standard Error 187
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Taurocholic acid
|
126.5 ng/ml x h
Standard Error 30.2
|
248.1 ng/ml x h
Standard Error 39.5
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Tauroursodeoxycholic acid
|
15.03 ng/ml x h
Standard Error 3.17
|
17.07 ng/ml x h
Standard Error 3.33
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Cholic acid
|
212.0 ng/ml x h
Standard Error 46.3
|
259.7 ng/ml x h
Standard Error 64.6
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Deoxycholic acid
|
1366 ng/ml x h
Standard Error 314
|
1222 ng/ml x h
Standard Error 158
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Glycodeoxycholic acid
|
1618 ng/ml x h
Standard Error 269
|
1507 ng/ml x h
Standard Error 200
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Taurodeoxycholic acid
|
233.3 ng/ml x h
Standard Error 36.9
|
329.3 ng/ml x h
Standard Error 53.1
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Chenodeoxycholic acid
|
5290 ng/ml x h
Standard Error 353
|
5552 ng/ml x h
Standard Error 471
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Glycochenodeoxycholic acid
|
6499 ng/ml x h
Standard Error 1122
|
7386 ng/ml x h
Standard Error 847
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Taurochenodeoxycholic acid
|
879.8 ng/ml x h
Standard Error 132.5
|
1393 ng/ml x h
Standard Error 195
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Lithocholic acid
|
70.10 ng/ml x h
Standard Error 10.74
|
67.64 ng/ml x h
Standard Error 14.64
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Glycolithocholic acid
|
164.3 ng/ml x h
Standard Error 30.3
|
192.1 ng/ml x h
Standard Error 57.8
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Taurolithocholic acid
|
17.39 ng/ml x h
Standard Error 3.00
|
21.02 ng/ml x h
Standard Error 4.55
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Ursodeoxycholic acid
|
283.5 ng/ml x h
Standard Error 168.9
|
243.7 ng/ml x h
Standard Error 159.7
|
|
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
Glycoursodeoxycholic acid
|
625.9 ng/ml x h
Standard Error 220.8
|
542.1 ng/ml x h
Standard Error 181.9
|
SECONDARY outcome
Timeframe: 0-10 hoursFor each of 15 endogenous bile acid, endogenous bile acid Cmax after polysorbate 80, compared to endogenous bile acid Cmax after placebo. Cmax units are concentration (i.e. ng/ml).
Outcome measures
| Measure |
Metformin
n=12 Participants
Participants took 500 mg metformin b.i.d. for 6 days. On day 7, participants were administered 80 mg pravastatin and 250 mg chenodeoxycholic acid.
|
Placebo
n=12 Participants
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Cholic acid
|
91.16 ng/ml
Standard Error 21.41
|
123.8 ng/ml
Standard Error 51.0
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Taurochenodeoxycholic acid
|
332.6 ng/ml
Standard Error 47.4
|
349.8 ng/ml
Standard Error 69.7
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Lithocholic acid
|
12.35 ng/ml
Standard Error 2.59
|
9.400 ng/ml
Standard Error 2.040
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Glycolithocholic acid
|
36.68 ng/ml
Standard Error 7.81
|
43.31 ng/ml
Standard Error 12.76
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Glycocholic acid
|
291.3 ng/ml
Standard Error 35.5
|
263.9 ng/ml
Standard Error 44.8
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Taurocholic acid
|
77.80 ng/ml
Standard Error 10.81
|
67.64 ng/ml
Standard Error 12.96
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Deoxycholic acid
|
270.9 ng/ml
Standard Error 49.4
|
199.7 ng/ml
Standard Error 28.6
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Glycodeoxycholic acid
|
385.7 ng/ml
Standard Error 43.5
|
375.7 ng/ml
Standard Error 50.9
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Taurodeoxycholic acid
|
92.58 ng/ml
Standard Error 13.42
|
86.14 ng/ml
Standard Error 16.50
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Chenodeoxycholic acid
|
3049 ng/ml
Standard Error 280
|
2982 ng/ml
Standard Error 359
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Glycochenodeoxycholic acid
|
1396 ng/ml
Standard Error 175
|
1667 ng/ml
Standard Error 234
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Taurolithocholic acid
|
5.510 ng/ml
Standard Error 0.760
|
6.150 ng/ml
Standard Error 1.800
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Ursodeoxycholic acid
|
27.89 ng/ml
Standard Error 5.30
|
41.60 ng/ml
Standard Error 24.98
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Glycoursodeoxycholic acid
|
86.27 ng/ml
Standard Error 12.40
|
118.0 ng/ml
Standard Error 38.3
|
|
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
Tauroursodeoxycholic acid
|
5.360 ng/ml
Standard Error 0.770
|
5.010 ng/ml
Standard Error 0.930
|
Adverse Events
Metformin
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Polysorbate 80
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Metformin
n=13 participants at risk
Participants took 500 mg metformin for 6 days. On day 7, participants were administered the cocktail, which included 80 mg pravastatin and 250 mg CDCA.
|
Polysorbate 80
n=12 participants at risk
Participants took 400 mg polysorbate 80 b.i.d. for 6 days. On day 7, participants were administered the cocktail, which included 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 400 mg polysorbate 80.
|
Placebo
n=13 participants at risk
Participants took one placebo b.i.d. for 6 days. On day 7, participants were administered the cocktail, which included 500 mg valacyclovir, 250 mg CDCA, 20 mg enalaprilat, and 80 mg pravastatin.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
23.1%
3/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Nervous system disorders
Lightheaded and vision tunneling
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Hepatobiliary disorders
Elevated liver function tests
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Nervous system disorders
Vasovasgal syncope
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Gastrointestinal disorders
Easy bowel movement
|
15.4%
2/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
8.3%
1/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Gastrointestinal disorders
Stomach discomfort and uneasiness
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Gastrointestinal disorders
Stomach ache/pain
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Gastrointestinal disorders
Nausea
|
23.1%
3/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Nervous system disorders
Headache
|
15.4%
2/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Gastrointestinal disorders
Stomach cramping
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Hepatobiliary disorders
Mildly elevated alanine aminotransferase
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Gastrointestinal disorders
GI issues (tightness and not feeling regular)
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
General disorders
Fatigue
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Gastrointestinal disorders
Abdominal tightness
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Gastrointestinal disorders
Wet/runny stool
|
7.7%
1/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
|
Skin and subcutaneous tissue disorders
Itchy rash
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
8.3%
1/12 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
0.00%
0/13 • Approximately 6 weeks, which is the duration of participant participation in the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place