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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Soticlestat 300 mg + Rifampin 600 mg | Experimental | Soticlestat 3*100 mg tablets, orally, administered once on Day 1 in fasted state in Period 1, followed by a washout period of 4 days, further followed by Rifampin 600 mg, administered as 2*300mg capsules, orally, once daily for 13 consecutive days, from Day 1 to Day 13 in fasted state in Period 2. Soticlestat 3*100 mg tablets, will be administered orally along with rifampin 600 mg (2*300mg) capsules, orally in the morning of Day 11 in Period 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Soticlestat | Drug | Soticlestat tablets. |
|
| Measure | Description | 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 |
| Measure | Description | 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) |
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Inclusion criteria:
Exclusion criteria:
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.
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.
Unable to refrain from or anticipates the use of:
Appropriate sources (example, Flockhart TableTM) will be consulted to confirm lack of pharmacokinetic (PK)/pharmacodynamics interaction with study drug.
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).
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.
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.
Donation of blood or significant blood loss within 56 days prior to the first dosing.
Plasma donation within 7 days prior to the first dosing.
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.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Belfast | BT9 6AD | United Kingdom |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
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 took part in the study at 1 investigative site in United Kingdom from 22 November 2021 to 03 March 2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants: Soticlestat 300 mg + Rifampin 600 mg + Soticlestat 300 mg | Soticlestat 300 milligram (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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (1 Day) |
|
| ||||||||||||||||||
| Washout Period (4 Days) |
| |||||||||||||||||||
| Period 2 (13 Days) |
|
The safety set included all participants who received at least one dose of the study drug(s).
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Rifampin | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 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 |
|
TEAEs were adverse events (AE) that started from Day 1 of Period 1 up to 15 days after the last dose of Soticlestat in Period 2 (up to Day 31)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Soticlestat 300 mg Alone | Soticlestat 300 mg (3*100 mg) T4 tablet, orally, once on Day 1 in fasted state in Period 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bacteriuria | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 20, 2021 | Feb 17, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 16, 2021 | Feb 17, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000712808 | soticlestat |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Rifampin | Drug | Rifampin capsules. |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
|
| Weight | Mean | Standard Deviation | kilogram (kg) |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
|
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. |
|
|
|
| Primary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Rifampin | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter(ng*hr/mL) | 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 |
|
|
|
|
| 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 | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
|
|
|
|
| Primary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Rifampin | 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). | Posted | Median | Full Range | hour | 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 | Number of Participants Reported One or More Treatment-Emergent Adverse Events (TEAEs) | The safety set included all participants who received at least one dose of the study drug(s). | Posted | Count of Participants | Participants | From Day 1 of Period 1 up to 15 days after the last dose of Soticlestat in Period 2 (up to Day 31) |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 2 |
| 15 |
| EG001 | Rifampin 600 mg Alone | Rifampin 600 mg (2*300 mg), capsules, orally, once daily from Day 1 to Day 13 in fasted state in Period 2. | 0 | 14 | 0 | 14 | 1 | 14 |
| EG002 | Soticlestat 300 mg + Rifampin 600 mg | 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. | 0 | 14 | 0 | 14 | 2 | 14 |
| Catheter site erythema | General disorders | MedDRA 24.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 24.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
|
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |