Back to resultsA Phase 1 Study to Evaluate the Effects of Fluconazole and Atorvastatin on the Pharmacokinetics of TAK-385 in Healthy Subjects
Primary Purpose
Prostate Cancer, Endometriosis
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
TAK-385
Fluconazole
Atorvastatin
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
Inclusion Criteria
Each subject must meet all the following inclusion criteria to be enrolled in the study:
- Age 18 to 55 years, inclusive, at the time of consent.
- Healthy adult male or female in good health, as determined by a physician evaluation
- Weight ≥ 45 kg and body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening.
- 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.
- 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.
- 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.
- 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).
- 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.
- The subject has current or recent (within 6 months) history of gastrointestinal disease that would be expected to influence the absorption of drugs.
- 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.
- 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.
- The subject has abnormal laboratory values suggesting a clinically significant disease at screening or check-in (Day -1) .
- Female subjects who are lactating and breastfeeding or pregnant before the first dose of study drug.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
TAK-385 + fluconazole
TAK-385 + atorvastatin
Arm Description
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 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.
Outcomes
Primary Outcome Measures
Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 1
Cmax is the peak concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 10
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
Area under the plasma concentration versus time curve from zero to the time of the last quantifiable concentration.
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
Area under the plasma concentration versus time curve from zero to the time of the last quantifiable concentration.
AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 1
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
Area under the plasma concentration-time curve from time 0 to infinity.
Secondary Outcome Measures
Number of Participants With at Least 1 Treatment Emergent Adverse Event (AE)
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
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 Electrocardiogram (ECG) Findings
A 12-lead ECG was administered on Days 1,9,10,11,15.
Number of Participants With Clinical Significant Changes in Laboratory Tests
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
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
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
Terminal disposition half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Apparent Total Body Clearance (CL/F) of TAK-385
Fraction Excreted Unchanged (Fe) of TAK-385
Fraction of TAK-385 excreted in the urine unchanged.
Plasma Trough Concentrations for Fluconazole
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
Blood samples for atorvastatin trough levels were collected predose (before dosing with atorvastatin and before breakfast) on Days 8 through 12.
Full Information
NCT ID
NCT02093390
First Posted
March 19, 2014
Last Updated
June 1, 2016
Sponsor
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02093390
Brief Title
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
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Endometriosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TAK-385 + fluconazole
Arm Type
Experimental
Arm Description
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.
Arm Title
TAK-385 + atorvastatin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TAK-385
Intervention Description
TAK-385 tablets
Intervention Type
Drug
Intervention Name(s)
Fluconazole
Intervention Description
Fluconazole tablets
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Intervention Description
Atorvastatin tablets
Primary Outcome Measure Information:
Title
Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 1
Description
Cmax is the peak concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time Frame
Day 1 (Predose and multiple time points up to 120 hours postdose)
Title
Cmax: Maximum Observed Plasma Concentration of TAK-385 on Day 10
Description
Cmax is the peak concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time Frame
Day 10 (Predose and multiple time points up to 120 hours postdose)
Title
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
Description
Area under the plasma concentration versus time curve from zero to the time of the last quantifiable concentration.
Time Frame
Day 1 (Predose and multiple time points up to 120 hours postdose)
Title
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
Description
Area under the plasma concentration versus time curve from zero to the time of the last quantifiable concentration.
Time Frame
Day 10 (Predose and multiple time points up to 120 hours postdose)
Title
AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 1
Description
Area under the plasma concentration-time curve from time 0 to infinity.
Time Frame
Day 1 (Predose and multiple time points up to 120 hours postdose)
Title
AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-385 on Day 10
Description
Area under the plasma concentration-time curve from time 0 to infinity.
Time Frame
Day 10 (Predose and multiple time points up to 120 hours postdose)
Secondary Outcome Measure Information:
Title
Number of Participants With at Least 1 Treatment Emergent Adverse Event (AE)
Description
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.
Time Frame
First dose of study drug through the end of the study (22 days ± 3 days)
Title
Number of Participants With Clinical Significant Changes in Vital Signs
Description
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.
Time Frame
Baseline and First dose of study drug through the end of the study (22 days ± 3 days)
Title
Number of Participants With Clinical Significant Changes in Electrocardiogram (ECG) Findings
Description
A 12-lead ECG was administered on Days 1,9,10,11,15.
Time Frame
Baseline and First dose of study drug through Day 15
Title
Number of Participants With Clinical Significant Changes in Laboratory Tests
Description
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.
Time Frame
Baseline and First dose of study drug through the end of the study (22 days ± 3 days)
Title
Tmax: Time to Reach the Maximum Plasma Concentration of TAK-385
Description
Tmax is the time to reach the maximum concentrations (Cmax), equal to time (hours) to Cmax.
Time Frame
Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
Title
AUC (0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours of TAK-385
Description
Area under the plasma concentration versus time curve from 0 to 120 hours after study drug administration.
Time Frame
Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
Title
Terminal Disposition Half-life (t1/2) of TAK-385
Description
Terminal disposition half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time Frame
Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
Title
Apparent Total Body Clearance (CL/F) of TAK-385
Time Frame
Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
Title
Fraction Excreted Unchanged (Fe) of TAK-385
Description
Fraction of TAK-385 excreted in the urine unchanged.
Time Frame
Days 1 and 10 (Predose and multiple time points up to 120 hours postdose)
Title
Plasma Trough Concentrations for Fluconazole
Description
Blood samples for fluconazole trough levels were collected predose (before dosing with fluconazole and before breakfast) on Days 8 through 12.
Time Frame
Days 8 to 12 Predose
Title
Plasma Trough Concentrations for Atorvastatin
Description
Blood samples for atorvastatin trough levels were collected predose (before dosing with atorvastatin and before breakfast) on Days 8 through 12.
Time Frame
Days 8 to 12 Predose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria
Each subject must meet all the following inclusion criteria to be enrolled in the study:
Age 18 to 55 years, inclusive, at the time of consent.
Healthy adult male or female in good health, as determined by a physician evaluation
Weight ≥ 45 kg and body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening.
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.
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.
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.
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).
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.
The subject has current or recent (within 6 months) history of gastrointestinal disease that would be expected to influence the absorption of drugs.
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.
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.
The subject has abnormal laboratory values suggesting a clinically significant disease at screening or check-in (Day -1) .
Female subjects who are lactating and breastfeeding or pregnant before the first dose of study drug.
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Phase 1 Study to Evaluate the Effects of Fluconazole and Atorvastatin on the Pharmacokinetics of TAK-385 in Healthy Subjects
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