Healthy Participants
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the effect of the potent cytochrome P-450 (CYP) 3A4 inhibitor (itraconazole) on the single-dose PK of oral TAK-906 maleate.
Detailed description
The drug being tested in this study is called TAK-906. TAK-906 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-906 maleate. The study enrolled 12 participants. Participants received the following treatment sequence: • TAK-906 maleate 25 mg; Itraconazole 200 mg + TAK-906 maleate 25 mg Participants were given an oral dose of TAK-906 in the First Intervention Period which was followed by a washout period, after which participants were given Itraconazole solution along with TAK-906 orally in the Second Intervention Period. This single center trial was conducted in the United States. The overall duration to participate in this study was 7 weeks. Participants remained confined in the clinic from Day 1 up to Day 2 (First Intervention Period) and Day 4 up Day 6 (Second Intervention Period). Participants returned for a Follow-up Visit, 10 to 14 days after last dose of study drug.
Interventions
DRUGTAK-906 Maleate
TAK-906 capsule
DRUGItraconazole
Itraconazole solution
Sponsors
Millennium Pharmaceuticals, Inc.
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) greater than or equal to (\>=) 18 and less than or equal to (\<=) 30 kilogram per square meter (kg/m\^2) and 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. Has had a 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-906 | TAK-906 maleate 25mg: Day 1 pre-dose and at multiple time points (up to 48 hours) post-TAK-906 maleate-dose; Itraconazole 200 mg + TAK-906 maleate 25mg: Day 4 pre-dose and at multiple time points (up to 48 hours) post- TAK-906 maleate-dose |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906 | TAK-906 maleate 25mg: Day 1 pre-dose and at multiple time points (up to 48 hours) post-TAK-906 maleate-dose; Itraconazole 200 mg + TAK-906 maleate 25mg: Day 4 pre-dose and at multiple time points (up to 48 hours) post- TAK-906 maleate-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906 | TAK-906 maleate 25mg: Day 1 pre-dose and at multiple time points (up to 48 hours) post-TAK-906 maleate-dose; Itraconazole 200 mg + TAK-906 maleate 25mg: Day 4 pre-dose and at multiple time points (up to 48 hours) post- TAK-906 maleate-dose |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 05 June 2017 to 10 July 2017.
Pre-assignment details
Healthy participants were enrolled in single sequence 2-period crossover study to receive TAK-906 maleate 25 milligram (mg) in First Intervention Period followed by Itraconazole 200 mg along with TAK-906 maleate 25 mg in Second Intervention Period.
Participants by arm
| Arm | Count |
|---|---|
| TAK-906 Maleate 25mg;Itraconazole 200mg + TAK-906 Maleate 25mg TAK-906 maleate 25 mg, capsule, orally, once on Day 1 of First Intervention Period, followed by a minimum of 4-day washout period, further followed by Itraconazole 200 mg, solution, orally, once daily on Days 1 to 5 along with TAK-906 maleate 25 mg, capsule, orally on Day 4 of Second Intervention Period. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Second Intervention Period (6 Days) | Positive urine drug screen | 1 |
Baseline characteristics
| Characteristic | TAK-906 Maleate 25mg;Itraconazole 200mg + TAK-906 Maleate 25mg |
|---|---|
| Age, Continuous | 32.3 years STANDARD_DEVIATION 7.25 |
| Body Mass Index (BMI) | 26.2 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 180.8 centimeter (cm) STANDARD_DEVIATION 6.79 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 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 | 4 Participants |
| Region of Enrollment United States | 12 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
| Weight | 85.4 kilogram (kg) STANDARD_DEVIATION 10.59 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 12 | 1 / 11 | 1 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 | 0 / 11 |
Outcome results
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906
Time frame: TAK-906 maleate 25mg: Day 1 pre-dose and at multiple time points (up to 48 hours) post-TAK-906 maleate-dose; Itraconazole 200 mg + TAK-906 maleate 25mg: Day 4 pre-dose and at multiple time points (up to 48 hours) post- TAK-906 maleate-dose
Population: The PK analysis set included all participants from the safety set who had at least 1 measurable post-dose TAK-906 plasma concentration. PK analysis set where Day 1 and 4 assessments were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-906 Maleate 25 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906 | 24.41 h*ng/mL | Standard Deviation 8.136 |
| Itraconazole 200 mg + TAK-906 Maleate 25 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906 | 31.45 h*ng/mL | Standard Deviation 8.995 |
Comparison: A paired t-test on the natural log-transformed parameters was performed. The mean difference and its 90% CI for the log-transformed parameters were exponentiated to obtain the point estimates of the itraconazole effect and 90% CIs.90% CI: [1.0965, 1.4904]
Primary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906
Time frame: TAK-906 maleate 25mg: Day 1 pre-dose and at multiple time points (up to 48 hours) post-TAK-906 maleate-dose; Itraconazole 200 mg + TAK-906 maleate 25mg: Day 4 pre-dose and at multiple time points (up to 48 hours) post- TAK-906 maleate-dose
Population: The PK analysis set included all participants from the safety set who had at least 1 measurable post-dose TAK-906 plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-906 Maleate 25 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906 | 24.10 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 8.173 |
| Itraconazole 200 mg + TAK-906 Maleate 25 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906 | 30.73 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 8.521 |
Comparison: A paired t-test on the natural log-transformed parameters was performed. The mean difference and its 90% CI for the log-transformed parameters were exponentiated to obtain the point estimates of the itraconazole effect and 90% CIs.90% CI: [1.1199, 1.4891]
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-906
Time frame: TAK-906 maleate 25mg: Day 1 pre-dose and at multiple time points (up to 48 hours) post-TAK-906 maleate-dose; Itraconazole 200 mg + TAK-906 maleate 25mg: Day 4 pre-dose and at multiple time points (up to 48 hours) post- TAK-906 maleate-dose
Population: The pharmacokinetic (PK) analysis set included all participants from the safety set who had at least 1 measurable post-dose TAK-906 plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TAK-906 Maleate 25 mg | Cmax: Maximum Observed Plasma Concentration for TAK-906 | 9.532 nanogram per milliliter (ng/mL) | Standard Deviation 4.6337 |
| Itraconazole 200 mg + TAK-906 Maleate 25 mg | Cmax: Maximum Observed Plasma Concentration for TAK-906 | 17.999 nanogram per milliliter (ng/mL) | Standard Deviation 4.878 |
Comparison: A paired t-test on the natural log-transformed parameters was performed. The mean difference and its 90 percent (%) confidence interval (CI) for the log-transformed parameters were exponentiated to obtain the point estimates of the itraconazole effect and 90% CIs.90% CI: [1.6446, 2.3904]