Healthy Participants
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the effect of the potent CYP3A4 inhibitor itraconazole on the single-dose PK of TAK-954.
Detailed description
The drug being tested in this study is called TAK-954. TAK-954 is being tested in healthy participants in order to evaluate the effect of the potent CYP3A4 inhibitor itraconazole on the single-dose PK of TAK-954. The study will enroll approximately 10 participants. Participants will receive the following treatment sequences: • TAK-954 0.2 mg; Itraconazole 200 mg + TAK-954 0.2 mg Participants will be given an intravenous infusion of TAK-954 on Day 1 of First Intervention Period (6 days) followed by minimum 7-day washout period, after which participants will be given Itraconazole capsule on Days 1 to 8 along with TAK-945 infusion on Day 4 of Second Intervention Period (9 days). This single center trial will be conducted in the United States. The overall duration to participate in this study is 7 to 8 weeks. Participants will visit the clinic on Day -1 and remained confined until Day 6 (First Intervention Period) and Day 9 (Second Intervention Period). Participants will return for a Follow-up Visit 10 to 14 days after last dose of study drug (approximately up to Day 34).
Interventions
DRUGTAK-954
TAK-954 Infusion
DRUGItraconazole
Itraconazole Capsule
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is a man or woman (with no child bearing potential) aged 18 to 55 years, inclusive, at the Screening Visit. 2. Has a body mass index (BMI) from greater than or equal to (\>=) 18 and less than or equal to (\<=) 30 kilogram per square meter (kg/m\^2) and has a body weight greater than (\>) 50 kilogram (kg) at the Screening Visit. 3. Is a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before administration of the initial dose of trial drug/invasive procedure.
Exclusion criteria
1. Has a positive alcohol or drug screen. 2. Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter (mL)) within 8 weeks of the first dose of study drug. 3. Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\] per day). 4. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. 5. Has a substance abuse disorder.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-954 | TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2 mg: Day 4 pre-dose and at multiple time points (up to 120 hours) post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 | TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in United States from 31 May 2017 to 24 July 2017.
Pre-assignment details
Healthy participants were enrolled in this single sequence 2-period crossover study to receive TAK-954 0.2 milligram (mg) in Intervention Period 1 followed by itraconazole 200 mg + TAK-954 0.2 mg in Intervention Period 2.
Participants by arm
| Arm | Count |
|---|---|
| TAK-954 0.2 mg + Itraconazole 200 mg and TAK-954 0.2mg TAK-954 0.2 mg, infusion, intravenously, once on Day 1 of First Intervention Period, followed by a minimum of 7-day washout period, further followed by itraconazole 200 mg, capsule, orally, once daily on Days 1 to 8 along with TAK-954 0.2 mg, infusion, intravenously on Day 4 of Second Intervention Period. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | TAK-954 0.2 mg + Itraconazole 200 mg and TAK-954 0.2mg |
|---|---|
| Age, Continuous | 34.7 years STANDARD_DEVIATION 10.34 |
| Body mass index (BMI) | 24.2 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 174.4 centimeter (cm) STANDARD_DEVIATION 10.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 9 Participants |
| Weight | 73.72 kilogram (kg) STANDARD_DEVIATION 11.534 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 3 / 10 | 0 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954
Time frame: TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Population: The PK set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration. PK analysis set where Day 1 and 4 assessments were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-954 0.2 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 | 28.59 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 6.55 |
| Itraconazole 200 mg and TAK-954 0.2 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 | 43.15 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 10.265 |
Comparison: A paired t-test on the natural log-transformed parameters was performed. The means and difference of means for the log-transformed parameters were exponentiated to obtain the point estimates of the itraconazole effect and 90% CIs.90% CI: [1.3851, 1.6012]
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-954
Time frame: TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2 mg: Day 4 pre-dose and at multiple time points (up to 120 hours) post-dose
Population: The pharmacokinetic (PK) set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-954 0.2 mg | Cmax: Maximum Observed Plasma Concentration for TAK-954 | 2.642 nanogram/milliliter (ng/mL) | Standard Deviation 0.4426 |
| Itraconazole 200 mg and TAK-954 0.2 mg | Cmax: Maximum Observed Plasma Concentration for TAK-954 | 2.840 nanogram/milliliter (ng/mL) | Standard Deviation 0.6497 |
Comparison: A paired t-test on the natural log-transformed parameters was performed. The means and difference of means for the log-transformed parameters were exponentiated to obtain the point estimates of the itraconazole effect and 90 percent (%) confidence intervals (CIs).90% CI: [0.9569, 1.1792]