Clinical trial NCT05064449: A Study of Soticlestat With Itraconazole and Mefenamic Acid in Healthy Adults
Official title: A Phase 1, Open-Label Study to Evaluate the Effect of Itraconazole and Mefenamic Acid on the Single-Dose Pharmacokinetic Profile of Soticlestat in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-10-01
Enrollment: 28
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main aim of this study is to check how itraconazole and mefenamic acid affect the way soticlestat is processed by the body.

The study will have 2 parts. Participants can only participate in one study part.

Part 1: Participants will check into the study clinic to receive soticlestat, four days later they will begin receiving itraconazole and will stay in the clinic for 11 more days, receiving soticlestat in combination with itraconazole on one of those days. Participants will be contacted about 8 days after leaving the clinic for follow-up.

Part 2: Participants will check into the study clinic to receive soticlestat, four days later they will begin receiving mefenamic acid and will stay in the clinic for 7 more days, receiving soticlestat in combination with mefenamic acid on one of those days.. Participants will be contacted about 9 days after leaving the clinic for follow-up.

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 either itraconazole or mefenamic acid in healthy participants.

The study will be conducted in 2 parts: Part 1 (drug-drug interaction \[DDI\] with itraconazole), Part 2 (DDI with mefenamic acid). The study will enroll approximately 28 participants. Participants will be enrolled into two parts (Part 1 and Part 2) to receive soticlestat along with adjunctive therapy itraconazole and mefenamic acid as:

* Part 1: Soticlestat 300 mg + Itraconazole 200 mg
* Part 2: Soticlestat 300 mg + Mefenamic Acid 500 mg (first dose only) and 250 mg (subsequent doses)

Both Parts 1 and 2 will have two period (Periods 1 and 2). In Period 1, participants will receive only soticlestat (study drug) and in Period 2, participants will receive study drug along with either itraconazole or mefenamic acid depending upon in which part they are in. The data will be collected and stored in electronic case report form (eCRF).

This single-center trial will be conducted in the United States. The overall duration of the study is approximately 52 days for participants in Part 1 (includes screening and follow-up), but 48 days for participants in Part 2 (including screening and follow-up). There will be follow up for all participants approximately 15 days after the last dose of soticlestat in each study part.

Eligibility criteria: Inclusion Criteria:

1. Has body mass index (BMI) greater than or equal to (\>=) 18.0 and less than or equal to (\<=) 32.0 kilogram per meter square (kg/m\^2) at screening.
2. Continuous non-smoker who has not used nicotine-containing products for at least 90 days prior to the first dosing.
3. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECGs), as deemed by the Investigator or designee.

   * Supine blood pressure is \>=90/40 millimeter of mercury (mmHg) and \<=140/90 mmHg at screening;
   * Supine pulse rate is \>=45 beats per minute (bpm) and \<=100 bpm at screening;
   * QT interval corrected for pulse rate using Fridericia's formula (QTcF) is \<=450 millisecond (msec) (males) or \<=470 msec (females) and ECG findings considered normal or not clinically significant by the Investigator or designee at screening;
   * Estimated creatinine clearance \>=80 milliliter per minute (mL/min) at screening;
   * Liver function tests including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \<=1.5\*the upper limit of normal (ULN) at screening and check-in.
4. Able to swallow multiple tablets.

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 participants by their participation in the study.
2. Has history or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
3. Has history or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
4. 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.
5. Has 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).
6. 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.
7. 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.
8. Donation of blood or significant blood loss within 56 days prior to the first dosing.
9. Plasma donation within 7 days prior to the first dosing.
10. Has participation in another clinical study within 30 days or 5 half-lives prior to the first dosing. The 30-day 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.

Primary outcomes:
measure: Part 1, Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Itraconazole
timeFrame: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose
measure: Part 2, Cmax: Maximum Observed Plasma Concentration for Soticlestat When Administered Alone and With Mefenamic Acid
timeFrame: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with mefenamic acid: Period 2, Day 2 pre-dose and at multiple timepoints (up to 144 hours) post-dose
measure: Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Itraconazole
timeFrame: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose
measure: Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Soticlestat When Administered Alone and With Mefenamic Acid
timeFrame: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with mefenamic acid: Period 2, Day 2 pre-dose and at multiple timepoints (up to 144 hours) post-dose
measure: Part 1, 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 Itraconazole
timeFrame: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose
measure: Part 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 Mefenamic Acid
timeFrame: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with mefenamic acid: Period 2, Day 2 pre-dose and at multiple timepoints (up to 144 hours) post-dose
measure: Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Itraconazole
timeFrame: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with itraconazole: Period 2, Day 5 pre-dose and at multiple timepoints (up to 168 hours) post-dose
measure: Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Soticlestat When Administered Alone and With Mefenamic Acid
timeFrame: Soticlestat alone: Period 1, Day 1 pre-dose and at multiple timepoints (up to 96 hours) post-dose; Soticlestat with mefenamic acid: Period 2, Day 2 pre-dose and at multiple timepoints (up to 144 hours) post-dose
Secondary outcomes:
measure: Parts 1 and 2: Number of Participants Reported One or More Treatment-emergent Adverse Event (TEAE)
timeFrame: Part 1: from Day 1 of Period 1 up to 15 days after the last dose of soticlestat in Period 2 (up to Day 20 in Period 2); Part 2: from Day 1 of Period 1 up to 15 days after the last dose of soticlestat in Period 2 (up to Day 17 in Period 2)
measure: Parts 1 and 2: Number of Participants With Clinically Significant Abnormal Values for Laboratory Evaluations
timeFrame: Part 1: Day 1 of Period 1 up to Day 12 of Period 2; Part 2: Day 1 of Period 1 up to Day 8 of Period 2
measure: Parts 1 and 2: Number of Participants With Clinically Significant Abnormal Values for Vital Signs
timeFrame: Part 1: Day 1 of Period 1 up to Day 12 of Period 2; Part 2: Day 1 of Period 1 up to Day 8 of Period 2
measure: Parts 1 and 2: Number of Participants With Clinically Significant Abnormal Values for Electrocardiogram (ECG)
timeFrame: Part 1: Day 1 of Period 1 up to Day 12 of Period 2; Part 2: Day 1 of Period 1 up to Day 8 of Period 2
measure: Parts 1 and 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Part 1: Day 1 of Period 1 up to Day 12 of Period 2; Part 2: Day 1 of Period 1 up to Day 8 of Period 2
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: