Trial Outcomes & Findings for Pharmacokinetic Drug-Drug Interaction Study to Identify Biomarkers of Kidney Transporters (NCT NCT05365451)

Results Overview

baseline metformin area under the concentration vs. time curve (AUC)

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

16 participants

Primary outcome timeframe

0-24 hours

Results posted on

2025-08-08

Participant Flow

Participant milestones

Participant milestones
Measure	Metformin Alone, Then Cimetidine + Metformin, Then Furosemide Alone, Then Probenecid + Furosemide 16 subjects were administered 50 mg metformin as a solution for Part 1 Arm A. The same 16 subjects were administered 400 mg cimetidine as a tablet, then 50 mg metformin as a solution for Part 1 Arm B. The same 16 subjects were administered 5 mg furosemide as a tablet for Part 2 Arm A. The same 16 subjects were administered 1000 mg probenecid as a tablet, then 5 mg furosemide as a tablet for Part 2 Arm B.
Overall Study STARTED	16
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetic Drug-Drug Interaction Study to Identify Biomarkers of Kidney Transporters

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race/Ethnicity, Customized White	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	1 Participants n=5 Participants
Region of Enrollment United States	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0-24 hours

baseline metformin area under the concentration vs. time curve (AUC)

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Metformin Area Under the Concentration vs. Time Curve (AUC)	830 mcg*h/L Interval 710.0 to 970.0

PRIMARY outcome

Timeframe: 0-24 hours

Metformin area under the concentration vs. time curve (AUC) in presence of cimetidine

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Metformin AUC in Presence of Cimetidine	1030 mcg*h/L Interval 875.0 to 1210.0

PRIMARY outcome

Timeframe: 0-24 hours

baseline metformin maximum concentration (Cmax)

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Metformin Maximum Concentration (Cmax)	124 mcg/L Interval 107.0 to 143.0

PRIMARY outcome

Timeframe: 0-24 hours

metformin Cmax in the presence of cimetidine

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Metformin Cmax in Presence of Cimetidine	168 mcg/L Interval 145.0 to 195.0

PRIMARY outcome

Timeframe: 0-24 hours

baseline metformin renal clearance (CLr)

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Metformin Renal Clearance (CLr)	31 L/h Interval 27.0 to 34.0

PRIMARY outcome

Timeframe: 0-24 hours

metformin CLr in the presence of cimetidine

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Metformin CLr in Presence of Cimetidine	28 L/h Interval 25.0 to 31.0

PRIMARY outcome

Timeframe: 0-24 hours

baseline furosemide area under the concentration vs. time curve (AUC)

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Furosemide Area Under the Concentration vs. Time Curve (AUC)	462.4 ng.h/mL Interval 338.3 to 586.5

PRIMARY outcome

Timeframe: 0-24 hours

furosemide AUC in the presence of probenecid

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Furosemide AUC in Presence of Probenecid	854.6 ng.h/mL Interval 608.5 to 1100.7

PRIMARY outcome

Timeframe: 0-24 hours

baseline furosemide renal clearance (CLr)

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Furosemide Renal Clearance (CLr)	96.1 mL/min Interval 68.7 to 123.5

PRIMARY outcome

Timeframe: 0-24 hours

furosemide CLr in the presence of probenecid

Outcome measures

Outcome measures
Measure	Arm 1A - Arm 2A - Arm 1B - Arm 2B n=16 Participants 16 subjects completed Part 1, Arms A and B, then Part 2, Arms A and B, in that order.
Furosemide CLr in Presence of Probenecid	33.4 mL/min Interval 24.2 to 42.6

Adverse Events

Metformin Alone

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Cimetidine + Metformin

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Furosemide Alone

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Probenecid + Furosemide

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Metformin Alone n=16 participants at risk 16 subjects were administered 50 mg metformin as a solution for Part 1 Arm A.	Cimetidine + Metformin n=16 participants at risk The same 16 subjects were administered 400 mg cimetidine as a tablet, then 50 mg metformin as a solution for Part 1 Arm B.	Furosemide Alone n=16 participants at risk The same 16 subjects were administered 5 mg furosemide as a tablet for Part 2 Arm A.	Probenecid + Furosemide n=16 participants at risk The same 16 subjects were administered 1000 mg probenecid as a tablet, then 5 mg furosemide as a tablet for Part 2 Arm B.
Nervous system disorders Headache	6.2% 1/16 • Number of events 1 • 10 months	0.00% 0/16 • 10 months	12.5% 2/16 • Number of events 2 • 10 months	18.8% 3/16 • Number of events 3 • 10 months
Nervous system disorders nausea/vomiting	0.00% 0/16 • 10 months	0.00% 0/16 • 10 months	0.00% 0/16 • 10 months	6.2% 1/16 • Number of events 1 • 10 months
Skin and subcutaneous tissue disorders IV site tenderness	0.00% 0/16 • 10 months	0.00% 0/16 • 10 months	6.2% 1/16 • Number of events 1 • 10 months	0.00% 0/16 • 10 months
Nervous system disorders Neck discomfort	0.00% 0/16 • 10 months	6.2% 1/16 • Number of events 1 • 10 months	0.00% 0/16 • 10 months	0.00% 0/16 • 10 months

Additional Information

Dr. Mary Paine

Washington State University

Phone: 509-358-7759

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place