A Study of Soticlestat and Rifampin in Healthy Adults

A Phase 1 Open-Label Study to Evaluate the Drug-Drug Interaction of Rifampin as a Strong CYP3A Inducer on Soticlestat Pharmacokinetics in Healthy Adult Participants

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Soticlestat; Drug: Rifampin

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 6AD
    • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Soticlestat 300 mg + Rifampin 600 mg; 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.

Drug: Soticlestat; Soticlestat tablets.; Other Names: TAK-935; Drug: Rifampin; Rifampin capsules.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2021
• Primary Completion (Actual): February 16, 2022
• Study Completion (Actual): March 3, 2022

Study Registration Dates

• First Submitted: October 20, 2021
• First Submitted That Met QC Criteria: October 20, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin
• Other Study ID Numbers: TAK-935-1009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No