Trial Outcomes & Findings for The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine (NCT NCT03746106)

Last Updated: 2025-01-03

Results Overview

Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle. Cmax is determined by taking blood samples at various time points after drug administration and analyzing the thiamine concentration in plasma.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

7 participants

Primary outcome timeframe

The highest concentration of a thiamine observed in the blood plasma after drug administration

Results posted on

2025-01-03

Participant Flow

7 subjects were randomized into one of two arms; each arm had two cycles (which were separated by a washout period of 5-14 days), and each cycle was three days in duration. During the Cycle 1, subjects were administered either a) 5 mg thiamine (n = 4) or b) 5 mg thiamine and 300 mg trimethoprim with 500 mL of water (n = 3). And during the Cycle 2, patients receive the other treatment.

Participant milestones

Participant milestones
Measure	Thiamine Alone, Then Thiamine Co-administered With Trimethoprim One day prior to each study visit, participants arrived to collect three thiamine-deficient meals. They were instructed to consume these meals throughout the day, abstaining from other food intake. After an overnight fast, participants returned for their scheduled visit. On the first visit, they received 5 mg thiamine in 500 mL of water. Following a 5-14 day washout period, they repeated the process, this time receiving a combination of 5 mg thiamine and 300 mg trimethoprim with 500 mL of water.	Thiamine Co-administered With Trimethoprim, Then Thiamine Alone One day prior to each study visit, participants arrived to collect three thiamine-deficient meals. They were instructed to consume these meals throughout the day, abstaining from other food intake. After an overnight fast, participants returned for their scheduled visit. On the first visit, they received a combination of 5 mg thiamine and 300 mg trimethoprim with 500 mL of water. Following a 5-14 day washout period, they repeated the process, this time receiving a 5 mg thiamine in 500 mL of water.
Cycle 1 STARTED	4	3
Cycle 1 COMPLETED	4	3
Cycle 1 NOT COMPLETED	0	0
Cycle 2 STARTED	4	3
Cycle 2 COMPLETED	4	3
Cycle 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Thiamine Alone, Thiamine Co-administered With Trimethoprim n=7 Participants Subjects were randomized into one of two arms; each arm had two cycles (which were separated by a washout period of 5-14 days), and each cycle was three days in duration. During the Cycle 1, subjects were administered either a) 5 mg thiamine (n = 4) or b) 5 mg thiamine and 300 mg trimethoprim with 500 mL of water (n = 3). And during the Cycle 2, patients receive the other treatment.
Age, Continuous	46 years STANDARD_DEVIATION 15 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Weight	76 kg STANDARD_DEVIATION 16 • n=5 Participants
Height	170 cm STANDARD_DEVIATION 7.3 • n=5 Participants
BMI	26.4 kg/m^2 STANDARD_DEVIATION 4.6 • n=5 Participants
Baseline Thiamine (Thiamine arm)	12.3 nM STANDARD_DEVIATION 24.0 • n=5 Participants
Baseline Thiamine (Trimethoprim + Thiamine arm)	4.5 nM STANDARD_DEVIATION 4.3 • n=5 Participants

PRIMARY outcome

Timeframe: The highest concentration of a thiamine observed in the blood plasma after drug administration

Outcome measures

Outcome measures
Measure	Thiamine Alone n=7 Participants Participants who received 5 mg thiamine in 500 mL of water in either the first or second cycle of the study.	Thiamine Co-administered With Trimethoprim n=7 Participants Participants who received a combination of 5 mg thiamine and 300 mg trimethoprim with 500 mL of water in either the first or second cycle of the study.
Maximum Concentration (Cmax) of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm	15 nM Standard Deviation 9.5	32 nM Standard Deviation 22

PRIMARY outcome

Timeframe: Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle.

Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle. AUC0-24 (Area Under the Curve from 0 to 24 hours) is a pharmacokinetic (PK) parameter that represents the total drug exposure in the body over a 24-hour period. It is calculated as the area under the plasma thiamine concentration vs. time curve (from time zero to 24 hours after drug administration).

Outcome measures

Outcome measures
Measure	Thiamine Alone n=7 Participants Participants who received 5 mg thiamine in 500 mL of water in either the first or second cycle of the study.	Thiamine Co-administered With Trimethoprim n=7 Participants Participants who received a combination of 5 mg thiamine and 300 mg trimethoprim with 500 mL of water in either the first or second cycle of the study.
Area Under the Curve From 0 to 24 (AUC0-24)Hours of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm	50 nM*hr Standard Deviation 30	189 nM*hr Standard Deviation 138

Adverse Events

Thiamine Alone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Thiamine Co-administered With Trimethoprim

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Kathleen Giacomini

University of California, San Francisco

Phone: 4155144363

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place