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

Phase 1

Completed

Conditions: Prostate Cancer
Endometriosis

Interventions: Drug: TAK-385
Drug: Fluconazole
Drug: Atorvastatin

Registration Number: NCT02093390

Lead Sponsor: Millennium Pharmaceuticals, Inc.

Brief Summary: This is a nonrandomized, open-label, fixed-sequence, 2-arm study designed to assess the effect of multiple doses of fluconazole or atorvastatin on the single-dose pharmacokinetics of TAK-385 in healthy adult subjects.

Detailed Description: The drug being tested in this study is called TAK-385. TAK-385 was being tested to assess if the way it is processed the body changes when it administered with other medications (fluconazole or atorvastatin). This study looked at lab results in people who took TAK-385.

The study enrolled 40 patients. Participants were assigned to one of the two treatment groups:

* TAK-385 40 mg and fluconazole 400 mg on Day 6 and 200 mg on Days 7 to 14

* TAK-385 40 mg and atorvastatin 80 mg on Days 6-14

Participants in the fluconazole arm were administered TAK-385 on Days 1 and 10 and fluconazole on Days 6 through 14. Participants in the atorvastatin arm were administered TAK-385 on Days 1 and 10 and atorvastatin on Days 6 through 14.

This single-center trial was conducted in the United States. The overall time to participate in this study was 4 weeks. Participants made multiple visits to the clinic, including one 16-day period of confinement to the clinic, and a final visit 7 days after last dose of study drug for a follow-up assessment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TAK-385 + fluconazole	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	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.
TAK-385 + atorvastatin	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.
TAK-385 + fluconazole	TAK-385	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.

Primary Outcome Measures

Name	Time	Method
Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 10	Day 10 (Predose and multiple time points up to 120 hours postdose)	Cmax is the peak concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
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	Day 1 (Predose and multiple time points up to 120 hours postdose)	Area under the plasma concentration versus time curve from zero to the time of the last quantifiable concentration.
Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 1	Day 1 (Predose and multiple time points up to 120 hours postdose)	Cmax is the peak concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 1	Day 1 (Predose and multiple time points up to 120 hours postdose)	Area under the plasma concentration-time curve from time 0 to infinity.
AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 10	Day 10 (Predose and multiple time points up to 120 hours postdose)	Area under the plasma concentration-time curve from time 0 to infinity.
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	Day 10 (Predose and multiple time points up to 120 hours postdose)	Area under the plasma concentration versus time curve from zero to the time of the last quantifiable concentration.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Significant Changes in Electrocardiogram (ECG) Findings	Baseline and First dose of study drug through Day 15	A 12-lead ECG was administered on Days 1,9,10,11,15.
Apparent Total Body Clearance (CL/F) of TAK-385	Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
Fraction Excreted Unchanged (Fe) of TAK-385	Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)	Fraction of TAK-385 excreted in the urine unchanged.
Number of Participants With at Least 1 Treatment Emergent Adverse Event (AE)	First dose of study drug through the end of the study (22 days ± 3 days)	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.
Number of Participants With Clinical Significant Changes in Vital Signs	Baseline and First dose of study drug through the end of the study (22 days ± 3 days)	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.
Number of Participants With Clinical Significant Changes in Laboratory Tests	Baseline and First dose of study drug through the end of the study (22 days ± 3 days)	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.
Tmax: Time to Reach the Maximum Plasma Concentration of TAK-385	Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)	Tmax is the time to reach the maximum concentrations (Cmax), equal to time (hours) to Cmax.
AUC (0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours of TAK-385	Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)	Area under the plasma concentration versus time curve from 0 to 120 hours after study drug administration.
Terminal Disposition Half-life (t1/2) of TAK-385	Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)	Terminal disposition half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Plasma Trough Concentrations for Fluconazole	Days 8 to 12 Predose	Blood samples for fluconazole trough levels were collected predose (before dosing with fluconazole and before breakfast) on Days 8 through 12.
Plasma Trough Concentrations for Atorvastatin	Days 8 to 12 Predose	Blood samples for atorvastatin trough levels were collected predose (before dosing with atorvastatin and before breakfast) on Days 8 through 12.