Trial Outcomes & Findings for A Phase 1 Study to Evaluate the Effects of Fluconazole and Atorvastatin on the Pharmacokinetics of TAK-385 in Healthy Subjects (NCT NCT02093390)

Results Overview

Cmax is the peak concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

Day 1 (Predose and multiple time points up to 120 hours postdose)

Results posted on

2016-06-06

Participant Flow

Participants took part in the study at one investigative site in the United States from 13 March 2014 to 19 April 2014

Healthy participants were enrolled equally in 1 of 2 treatment groups: TAK-385 + fluconazole or TAK-385 + atorvastatin.

Participant milestones

Participant milestones
Measure	TAK-385 + Fluconazole TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on Day 10 then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on Days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on Day 10 then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Overall Study STARTED	20	20
Overall Study COMPLETED	20	19
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	TAK-385 + Fluconazole TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on Day 10 then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on Days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on Day 10 then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

A Phase 1 Study to Evaluate the Effects of Fluconazole and Atorvastatin on the Pharmacokinetics of TAK-385 in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.	Total n=40 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 9.74 • n=5 Participants	40.2 years STANDARD_DEVIATION 9.71 • n=7 Participants	38.8 years STANDARD_DEVIATION 9.72 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized White	18 participants n=5 Participants	16 participants n=7 Participants	34 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	16 participants n=5 Participants	15 participants n=7 Participants	31 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Weight	70.77 kg STANDARD_DEVIATION 9.137 • n=5 Participants	71.96 kg STANDARD_DEVIATION 12.693 • n=7 Participants	71.36 kg STANDARD_DEVIATION 10.933 • n=5 Participants
Height	163.6 cm STANDARD_DEVIATION 11.51 • n=5 Participants	163.3 cm STANDARD_DEVIATION 12.10 • n=7 Participants	163.4 cm STANDARD_DEVIATION 11.65 • n=5 Participants
Body Mass Index (BMI)	26.466 kg/m^2 STANDARD_DEVIATION 2.296 • n=5 Participants	26.567 kg/m^2 STANDARD_DEVIATION 2.838 • n=7 Participants	26.516 kg/m^2 STANDARD_DEVIATION 2.548 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (Predose and multiple time points up to 120 hours postdose)

Population: Pharmacokinetic (PK)-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Cmax is the peak concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 1	10.9 ng/mL Standard Deviation 9.34	20.1 ng/mL Standard Deviation 15.1

PRIMARY outcome

Timeframe: Day 10 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Cmax is the peak concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 10	14.4 ng/mL Standard Deviation 10.7	14.1 ng/mL Standard Deviation 8.41

PRIMARY outcome

Timeframe: Day 1 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Area under the plasma concentration versus time curve from zero to the time of the last quantifiable concentration.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of TAK-385 on Day 1	87.4 ng*hr/mL Standard Deviation 38.1	116.0 ng*hr/mL Standard Deviation 56.3

PRIMARY outcome

Timeframe: Day 10 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Area under the plasma concentration versus time curve from zero to the time of the last quantifiable concentration.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of TAK-385 on Day 10	104.0 ng*hr/mL Standard Deviation 40.5	99.8 ng*hr/mL Standard Deviation 31.2

PRIMARY outcome

Timeframe: Day 1 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Area under the plasma concentration-time curve from time 0 to infinity.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 1	92.6 ng*hr/mL Standard Deviation 40.2	123.0 ng*hr/mL Standard Deviation 59.6

PRIMARY outcome

Timeframe: Day 10 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Area under the plasma concentration-time curve from time 0 to infinity.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 10	112.0 ng*hr/mL Standard Deviation 43.4	108.0 ng*hr/mL Standard Deviation 32.3

SECONDARY outcome

Timeframe: First dose of study drug through the end of the study (22 days ± 3 days)

Population: Safety population included all randomized participants with at least one dose of study drug.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Number of Participants With at Least 1 Treatment Emergent Adverse Event (AE)	5 participants	6 participants

SECONDARY outcome

Timeframe: Baseline and First dose of study drug through the end of the study (22 days ± 3 days)

Population: Safety population included all randomized participants with at least one dose of study drug.

Vital sign measurements included oral temperature, heart rate, supine (after 3 to 5 minutes in this position) and standing (after 3 to 5 minutes in this position) measurements of diastolic and systolic blood pressure.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Number of Participants With Clinical Significant Changes in Vital Signs	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and First dose of study drug through Day 15

A 12-lead ECG was administered on Days 1,9,10,11,15.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Number of Participants With Clinical Significant Changes in Electrocardiogram (ECG) Findings	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and First dose of study drug through the end of the study (22 days ± 3 days)

Population: Safety population included all randomized participants with at least one dose of study drug.

Blood samples were collected for analysis of clinical chemistry and hematological parameters and urine samples were obtained for urinalysis. Clinical laboratory evaluations were performed at central and /local laboratories.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Number of Participants With Clinical Significant Changes in Laboratory Tests	0 participants	0 participants

SECONDARY outcome

Timeframe: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Tmax is the time to reach the maximum concentrations (Cmax), equal to time (hours) to Cmax.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Tmax: Time to Reach the Maximum Plasma Concentration of TAK-385 Day 1 (n=20, 20)	1.00 hours Interval 0.5 to 6.0	1.00 hours Interval 0.492 to 2.01
Tmax: Time to Reach the Maximum Plasma Concentration of TAK-385 Day 10 (n=19, 19)	1.00 hours Interval 0.499 to 6.01	1.01 hours Interval 0.501 to 4.02

SECONDARY outcome

Timeframe: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Area under the plasma concentration versus time curve from 0 to 120 hours after study drug administration.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
AUC (0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours of TAK-385 Day 1 (n=20,19)	87.4 ng*hr/mL Standard Deviation 38.1	116.0 ng*hr/mL Standard Deviation 56.3
AUC (0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours of TAK-385 Day 10 (n=19,19)	104.0 ng*hr/mL Standard Deviation 40.5	99.8 ng*hr/mL Standard Deviation 31.2

SECONDARY outcome

Timeframe: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Terminal disposition half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Terminal Disposition Half-life (t1/2) of TAK-385 Day 1 (n=20, 19)	34.8 hours Standard Deviation 3.38	36.5 hours Standard Deviation 3.74
Terminal Disposition Half-life (t1/2) of TAK-385 Day 10 (n=19, 19)	39.2 hours Standard Deviation 3.57	41.1 hours Standard Deviation 5.11

SECONDARY outcome

Timeframe: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Apparent Total Body Clearance (CL/F) of TAK-385 Day 1 (n=20, 19)	502 liters/hour Standard Deviation 189	420 liters/hour Standard Deviation 244
Apparent Total Body Clearance (CL/F) of TAK-385 Day 10 (n=19, 19)	421 liters/hour Standard Deviation 186	406 liters/hour Standard Deviation 144

SECONDARY outcome

Timeframe: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Fraction of TAK-385 excreted in the urine unchanged.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Fraction Excreted Unchanged (Fe) of TAK-385 Day 1 (n=20, 19)	1.56 percent of TAK-385 Standard Deviation 0.720	1.99 percent of TAK-385 Standard Deviation 1.17
Fraction Excreted Unchanged (Fe) of TAK-385 Day 10 (n=20, 19)	1.61 percent of TAK-385 Standard Deviation 0.813	1.40 percent of TAK-385 Standard Deviation 0.426

SECONDARY outcome

Timeframe: Days 8 to 12 Predose

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Blood samples for fluconazole trough levels were collected predose (before dosing with fluconazole and before breakfast) on Days 8 through 12.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=20 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Plasma Trough Concentrations for Fluconazole Day 8	6330 ng/mL Standard Deviation 1100	—
Plasma Trough Concentrations for Fluconazole Day 9	6540 ng/mL Standard Deviation 1180	—
Plasma Trough Concentrations for Fluconazole Day 10	7030 ng/mL Standard Deviation 1270	—
Plasma Trough Concentrations for Fluconazole Day 11	7030 ng/mL Standard Deviation 1540	—
Plasma Trough Concentrations for Fluconazole Day 12	7200 ng/mL Standard Deviation 1560	—

SECONDARY outcome

Timeframe: Days 8 to 12 Predose

Population: PK-Evaluable population included all enrolled participants who received at least one dose of study drug and had data available for analysis of the PK parameters.

Blood samples for atorvastatin trough levels were collected predose (before dosing with atorvastatin and before breakfast) on Days 8 through 12.

Outcome measures

Outcome measures
Measure	TAK-385 + Fluconazole n=19 Participants TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
Plasma Trough Concentrations for Atorvastatin Day 8	0.742 ng/mL Standard Deviation 0.444	—
Plasma Trough Concentrations for Atorvastatin Day 9	0.753 ng/mL Standard Deviation 0.351	—
Plasma Trough Concentrations for Atorvastatin Day 10	0.702 ng/mL Standard Deviation 0.385	—
Plasma Trough Concentrations for Atorvastatin Day 11	0.559 ng/mL Standard Deviation 0.263	—
Plasma Trough Concentrations for Atorvastatin Day 12	0.536 ng/mL Standard Deviation 0.203	—

Adverse Events

TAK-385 + Fluconazole

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

TAK-385 + Atorvastatin

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Director, Clinical Science

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Publication restrictions are in place

Restriction type: OTHER

Measure	TAK-385 + Fluconazole n=20 participants at risk TAK-385 40 mg, tablet, orally once on Day 1 and fluconazole 400 mg, tablet, orally on Day 6 then 200 mg, tablet, orally once daily on Days 7 to 9 followed by a single dose of TAK-385 in combination with fluconazole 200 mg on 10 day then fluconazole 200 mg, tablet, orally once daily alone on Days 11 to 14.	TAK-385 + Atorvastatin n=20 participants at risk TAK-385 40 mg, tablet, orally once on Day 1 and atorvastatin 80 mg, tablet, orally once daily on days 6 to 9 followed by a single dose of TAK-385 in combination with atorvastatin 80 mg on 10 day then atorvastatin 80 mg, tablet, orally once daily alone on Days 11 to 14.
General disorders Application site dermatitis	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Arthropod bite	10.0% 2/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Excoriation	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Hypoaesthesia	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Somnolence	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Dermatitis contact	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Dry skin	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Erythema	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Papule	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	15.0% 3/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Pruritus generalised	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.0% 1/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	15.0% 3/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.0% 2/20 • Up to 25 days At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.