Trial Outcomes & Findings for The Effects of Multiple Dose Fluoxetine and Metabolites on CYP1A2, CYP2C19, CYP2D6 and CYP3A4 Activity (NCT NCT01361217)

Last Updated: 2018-06-29

Results Overview

Our primary outcome measure will be the interaction of fluoxetine with CYP3A4. A 50% increase in the AUC for lovastatin plus hydroxy-lovastatin acid (the active form of lovastatin) between treatment day 14 (study day 20) and control days (study day 2) is considered clinically significant.

Recruitment status

COMPLETED

Study phase

Target enrollment

10 participants

Primary outcome timeframe

The primary outcome will be assessed within 2 months after the last subject is enrolled or at 2 years from the start of study enrollment, which ever is sooner.

Results posted on

2018-06-29

Participant Flow

Participant milestones

Participant milestones
Measure	Fluoxetine DDI Only arm in the study. Successive Control (Study Days 1 and 3) and fluoxetine multiple-dose treatment (Study Days 16 and 18) Sessions. Fluoxetine: 1x20mg oral fluoxetine capsules by mouth daily on Study Day 5, then 3x20mg fluoxetine capsules by mouth daily on Study Days 6 through 18.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Effects of Multiple Dose Fluoxetine and Metabolites on CYP1A2, CYP2C19, CYP2D6 and CYP3A4 Activity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fluoxetine DDI n=10 Participants Only arm in the study. Successive Control (Study Days 1 and 3) and fluoxetine multiple-dose treatment (Study Days 16 and 18) Sessions. Fluoxetine: 1x20mg oral fluoxetine capsules by mouth daily on Study Day 5, then 3x20mg fluoxetine capsules by mouth daily on Study Days 6 through 18.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=99 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants
Age, Continuous	30 years STANDARD_DEVIATION 10 • n=99 Participants
Sex: Female, Male Female	5 Participants n=99 Participants
Sex: Female, Male Male	5 Participants n=99 Participants
Race/Ethnicity, Customized caucasian	8 participants n=99 Participants
Race/Ethnicity, Customized hispanic	1 participants n=99 Participants
Race/Ethnicity, Customized chicano	1 participants n=99 Participants
Region of Enrollment United States	10 participants n=99 Participants
weight	72 kg STANDARD_DEVIATION 14 • n=99 Participants

PRIMARY outcome

Timeframe: The primary outcome will be assessed within 2 months after the last subject is enrolled or at 2 years from the start of study enrollment, which ever is sooner.

Outcome measures

Outcome measures
Measure	Lovastatin AUC After Fluoxetine Dosing n=10 Participants Only arm in the study. Successive Control (Study Days 1 and 3) and fluoxetine multiple-dose treatment (Study Days 16 and 18) Sessions. Fluoxetine: 1x20mg oral fluoxetine capsules by mouth daily on Study Day 5, then 3x20mg fluoxetine capsules by mouth daily on Study Days 6 through 18.	Lovastatin Before Fluoxetine n=10 Participants control
Lovastatin AUC in the Presence of Fluoxetine	170 nmol*hr/L Standard Deviation 70	180 nmol*hr/L Standard Deviation 90

SECONDARY outcome

Timeframe: The secondary outcome will be assessed within 2 months after the last subject is enrolled or at 2 years from the start of study enrollment, which ever is sooner.

Our secondary outcome measure will be the interaction between fluoxetine and each CYP evaluated in the cocktail. A 50% increase in the AUC of caffeine (CYP1A2), dextromethorphan (CYP2D6), omeprazole (CYP2C19) or midazolam (CYP3A4) between treatment and control days is considered clinically significant. The interaction of fluoxetine with caffeine (CYP1A2) will be considered as a negative control for the study. These AUCs will be measured on study day 1 (control day) and study day 18

Outcome measures

Outcome measures
Measure	Lovastatin AUC After Fluoxetine Dosing n=10 Participants Only arm in the study. Successive Control (Study Days 1 and 3) and fluoxetine multiple-dose treatment (Study Days 16 and 18) Sessions. Fluoxetine: 1x20mg oral fluoxetine capsules by mouth daily on Study Day 5, then 3x20mg fluoxetine capsules by mouth daily on Study Days 6 through 18.	Lovastatin Before Fluoxetine control
AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine caffeine control AUC	43000 nmol*hr/L Standard Deviation 22000	—
AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine Caffeine treatment AUC	43000 nmol*hr/L Standard Deviation 15000	—
AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine dextromethophan control AUC	68 nmol*hr/L Standard Deviation 100	—
AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine Dextromethorphan treatment AUC	1850 nmol*hr/L Standard Deviation 800	—
AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine Omeprazole control AUC	1200 nmol*hr/L Standard Deviation 600	—
AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine omeprazole treatment AUC	8500 nmol*hr/L Standard Deviation 3600	—
AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine midazolam control AUC	30 nmol*hr/L Standard Deviation 27	—
AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine midazolam treatment AUC	24 nmol*hr/L Standard Deviation 17	—

Adverse Events

Fluoxetine DDI

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fluoxetine DDI n=10 participants at risk Only arm in the study. Successive Control (Study Days 1 and 3) and fluoxetine multiple-dose treatment (Study Days 16 and 18) Sessions. Fluoxetine: 1x20mg oral fluoxetine capsules by mouth daily on Study Day 5, then 3x20mg fluoxetine capsules by mouth daily on Study Days 6 through 18.
Psychiatric disorders anxiety	10.0% 1/10 • Number of events 1

Additional Information

Nina Isoherranen

University of Washington

Phone: 206-5432517

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place