Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The main aim of this study is to check how rifampin affects the way soticlestat is processed by the body. Participants will be required to stay at the study clinic for 18 consecutive days. On the first full day and 15th day, participants will take a single dose of soticlestat. Rifampin will be taken each day starting on the 5th day for 13 consecutive days. Clinic staff will follow up with each participant about 15 days after the last soticlestat dose to check for any side effects.
Detailed description
The drug being tested in this study is called soticlestat (TAK-935). The study will evaluate the safety and tolerability of soticlestat when co-administered with rifampin in healthy participants. The study will enroll 14 participants. The participants will be assigned to treatment group to receive following therapies: • Soticlestat 300 milligram (mg) + Rifampin 600 mg The study will have two periods: Period 1 and Period 2. In Period 1, participants will receive soticlestat in fasted condition while in Period 2 participants will receive soticlestat along with rifampin. The data will be collected and stored in electronic case report form (eCRF). This single-center trial will be conducted in the United Kingdom. The overall study duration of the study will be approximately 58 days including 28 days screening and follow up duration. There will be a follow up contact required for all participants approximately 15 days after the last dose of soticlestat.
Interventions
DRUGRifampin
Rifampin capsules.
DRUGSoticlestat
Soticlestat tablets.
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy, adult, male or female of non-childbearing potential, 18-55 years of age, inclusive, at screening. 2. Has body mass index (BMI) greater than or equal to (\>=) 18.0 and less than or equal to (\<=) 32.0 kilogram per square meter (kg/m\^2) at screening. 3. Continuous non-smoker who has not used nicotine-containing products for at least 90 days prior to the first dosing. 4. Able to swallow multiple tablets/capsules.
Exclusion criteria
1. Has history of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study. 2. Any positive responses on the C-SSRS that in the clinical judgment of the Investigator has a risk of suicide or has made a suicide attempt in the previous 12 months prior to the first dosing. 3. Unable to refrain from or anticipates the use of: * Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to first dosing. * Any drugs known to be significant inducers of cytochrome (CYP)3A, CYP2C19, UGT1A9 or UGT2B4 enzymes, and/or P-glycoprotein (P-gp), including St. John's Wort, within 28 days prior to the first dosing. Appropriate sources (example, Flockhart TableTM) will be consulted to confirm lack of pharmacokinetic (PK)/pharmacodynamics interaction with study drug. 4. History of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to the following: beer 354 milliliter \[mL\]/12 ounce \[oz\], wine \[118 mL/4 oz\], or distilled spirits \[29.5 mL/1 oz\] per day). 5. Consumes excessive amounts, defined as greater than 4 servings (1 serving is approximately equivalent to 120 mg of caffeine), of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. 6. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study. 7. Donation of blood or significant blood loss within 56 days prior to the first dosing. 8. Plasma donation within 7 days prior to the first dosing. 9. Participation in another clinical study within 30 days or 5 half-lives prior to the first dosing. The 30-days window or 5 half-lives will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Rifampin | Soticlestat Alone: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose in Period 1; Soticlestat with Rifampin: Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose in Period 2 |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Rifampin | Soticlestat Alone: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose in Period 1; Soticlestat with Rifampin: Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose in Period 2 |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat When Administered Alone and With Rifampin | Soticlestat Alone: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose in Period 1; Soticlestat with Rifampin: Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose in Period 2 |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Rifampin | Soticlestat Alone: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose in Period 1; Soticlestat with Rifampin: Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose in Period 2 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Reported One or More Treatment-Emergent Adverse Events (TEAEs) | From Day 1 of Period 1 up to 15 days after the last dose of Soticlestat in Period 2 (up to Day 31) |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in United Kingdom from 22 November 2021 to 03 March 2022.
Pre-assignment details
Healthy participants were enrolled in this 2-period study to receive soticlestat tablets alone in Period 1 and soticlestat tablets and rifampin capsules in Period 2 of the study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants: Soticlestat 300 mg + Rifampin 600 mg + Soticlestat 300 mg Soticlestat 300 mg (3\*100 mg) immediate-release (T4) tablet, orally, once on Day 1 in fasted state in Period 1, followed by a washout period of 4 days, further followed by Rifampin 600 mg (2\*300 mg), capsules, orally, once daily from Day 1 to Day 13 along with soticlestat 300 mg (3\*100 mg) T4 tablet, orally, once on Day 11 in fasted state in Period 2. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 (1 Day) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants: Soticlestat 300 mg + Rifampin 600 mg + Soticlestat 300 mg |
|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 10.07 |
| Body Mass Index (BMI) | 26.713 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.1941 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 173.9 centimeter (cm) STANDARD_DEVIATION 5.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 15 Participants |
| Region of Enrollment United Kingdom | 15 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 14 Participants |
| Weight | 80.72 kilogram (kg) STANDARD_DEVIATION 10.176 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 2 / 15 | 1 / 14 | 2 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 0 / 14 |
Outcome results
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Rifampin
Time frame: Soticlestat Alone: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose in Period 1; Soticlestat with Rifampin: Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose in Period 2
Population: The PK set included participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations). Here, overall number of participants analyzed signified those who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Soticlestat 300 mg Alone | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Rifampin | 1448 nanogram*hour per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 47 |
| Soticlestat 300 mg + Rifampin 600 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Rifampin | 226.2 nanogram*hour per milliliter(ng*hr/mL) | Geometric Coefficient of Variation 94 |
90% CI: [12.53, 21.5]
Primary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat When Administered Alone and With Rifampin
Time frame: Soticlestat Alone: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose in Period 1; Soticlestat with Rifampin: Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose in Period 2
Population: The PK set included participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Soticlestat 300 mg Alone | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat When Administered Alone and With Rifampin | 1290 ng*hr/mL | Geometric Coefficient of Variation 52.9 |
| Soticlestat 300 mg + Rifampin 600 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Soticlestat When Administered Alone and With Rifampin | 190.6 ng*hr/mL | Geometric Coefficient of Variation 88.2 |
90% CI: [11.94, 18.64]
Primary
Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Rifampin
Time frame: Soticlestat Alone: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose in Period 1; Soticlestat with Rifampin: Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose in Period 2
Population: The pharmacokinetic (PK) set included participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Soticlestat 300 mg Alone | Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Rifampin | 1364 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 63.6 |
| Soticlestat 300 mg + Rifampin 600 mg | Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Rifampin | 176.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 99.6 |
90% CI: [9.73, 17.79]
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Rifampin
Time frame: Soticlestat Alone: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose in Period 1; Soticlestat with Rifampin: Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose in Period 2
Population: The PK set included participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Soticlestat 300 mg Alone | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Rifampin | 0.504 hour |
| Soticlestat 300 mg + Rifampin 600 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Rifampin | 0.499 hour |
p-value: =0.079190% CI: [-0.202, 0]Wilcoxon Signed-Rank Test
Secondary
Number of Participants Reported One or More Treatment-Emergent Adverse Events (TEAEs)
Time frame: From Day 1 of Period 1 up to 15 days after the last dose of Soticlestat in Period 2 (up to Day 31)
Population: The safety set included all participants who received at least one dose of the study drug(s).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Soticlestat 300 mg Alone | Number of Participants Reported One or More Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| Soticlestat 300 mg + Rifampin 600 mg | Number of Participants Reported One or More Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
| Soticlestat 300 mg + Rifampin 600 mg | Number of Participants Reported One or More Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |