Clinical trial NCT02093390: A Phase 1 Study to Evaluate the Effects of Fluconazole and Atorvastatin on the Pharmacokinetics of TAK-385 in Healthy Subjects
Official title: A Phase 1, Open-Label, Drug-Drug Interaction Study to Evaluate the Effects of Multiple Oral Doses of Fluconazole and Atorvastatin on the Pharmacokinetics of a Single Oral Dose of TAK-385 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Endometriosis
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-03-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

Each subject must meet all the following inclusion criteria to be enrolled in the study:

1. Age 18 to 55 years, inclusive, at the time of consent.
2. Healthy adult male or female in good health, as determined by a physician evaluation
3. Weight ≥ 45 kg and body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening.
4. Nonsmoker and does not use tobacco-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, or nicotine patch or gum).

Exclusion Criteria Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.

1. The subject has a history of drug abuse (defined as any illicit drug use) within 1 year before screening or is unwilling to abstain from drugs throughout the study.
2. The subject is unwilling to agree to abstain from caffeine and alcohol-containing products from 72 hours before check-in (Day -1) to completion of the final assessment.
3. The subject has taken any prescription medicine or herbal preparations (eg, St John's wort) or received any immunizations within 30 days before check-in (Day -1).
4. The subject has taken any over the counter (OTC) medications or vitamin supplements within 14 days before check-in (Day -1). The subject is unwilling to agree to abstain from consumption of grapefruit or grapefruit-containing products from 72 hours before check-in (Day -1) to completion of the final assessment.
5. The subject has current or recent (within 6 months) history of gastrointestinal disease that would be expected to influence the absorption of drugs.
6. The subject has a positive test result for hepatitis B surface antigen, hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody or antigen, or serological reactions for syphilis at screening.
7. The subject has a clinically significant ECG abnormality at screening or check-in (Day -1) or a QTc interval (by Fridericia's correction) of 450 msec or greater, or the subject has a history of cardiac disease.
8. The subject has abnormal laboratory values suggesting a clinically significant disease at screening or check-in (Day -1) .
9. Female subjects who are lactating and breastfeeding or pregnant before the first dose of study drug.
10. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 1
timeFrame: Day 1 (Predose and multiple time points up to 120 hours postdose)
measure: Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 10
timeFrame: Day 10 (Predose and multiple time points up to 120 hours postdose)
measure: 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
timeFrame: Day 1 (Predose and multiple time points up to 120 hours postdose)
measure: 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
timeFrame: Day 10 (Predose and multiple time points up to 120 hours postdose)
measure: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 1
timeFrame: Day 1 (Predose and multiple time points up to 120 hours postdose)
measure: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 10
timeFrame: Day 10 (Predose and multiple time points up to 120 hours postdose)
Secondary outcomes:
measure: Number of Participants With at Least 1 Treatment Emergent Adverse Event (AE)
timeFrame: First dose of study drug through the end of the study (22 days ± 3 days)
measure: Number of Participants With Clinical Significant Changes in Vital Signs
timeFrame: Baseline and First dose of study drug through the end of the study (22 days ± 3 days)
measure: Number of Participants With Clinical Significant Changes in Electrocardiogram (ECG) Findings
timeFrame: Baseline and First dose of study drug through Day 15
measure: Number of Participants With Clinical Significant Changes in Laboratory Tests
timeFrame: Baseline and First dose of study drug through the end of the study (22 days ± 3 days)
measure: Tmax: Time to Reach the Maximum Plasma Concentration of TAK-385
timeFrame: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
measure: AUC (0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours of TAK-385
timeFrame: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
measure: Terminal Disposition Half-life (t1/2) of TAK-385
timeFrame: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
measure: Apparent Total Body Clearance (CL/F) of TAK-385
timeFrame: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
measure: Fraction Excreted Unchanged (Fe) of TAK-385
timeFrame: Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
measure: Plasma Trough Concentrations for Fluconazole
timeFrame: Days 8 to 12 Predose
measure: Plasma Trough Concentrations for Atorvastatin
timeFrame: Days 8 to 12 Predose
Other outcomes:
Locations:
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: