Clinical trial NCT04461483: A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Dose and Multiple Doses With Titration of TAK-935 in Healthy Japanese Participants
Official title: A Randomized, Double-blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Dose and Multiple Doses With Titration of TAK-935 in Healthy Japanese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-07-08
Enrollment: 33
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-935 with single ascending doses (Part 1) and multiple doses with titration (Part 2).

Detailed description: The drug being tested in this study is called TAK-935 tablet. TAK-935 tablet is being tested in Japanese healthy adult men. This study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-935 with single ascending doses (Part 1) and multiple doses with titration (Part 2).

The study will enroll up to 33 participants in total (Part 1 + 2). In Part 1, participants will be randomly assigned (by chance, like flipping a coin) to one of these treatment cohorts/groups;

* Cohort 1: Single dose of TAK-935 at 200 mg or placebo (fasted)
* Cohort 2: Single dose of TAK-935 at 600 mg or placebo (fasted)
* Cohort 3: Single dose of TAK-935 at 1200 mg or placebo (fasted)

In Part 2, participants will be randomly assigned to one of these treatment groups;

- Cohort 4: Multiple doses with titration of TAK-935 or placebo at 100 mg twice daily (BID) from Day 1 to Day 7, 200 mg BID from Day 8 to Day 14 and 300 mg BID from Day 15 to Day 21 (fasted).

This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately 36 days for Part 1 and 63 days for Part 2. Participants will be hospitalized for 5 days in Part 1 and 26 days in Part 2.

Eligibility criteria: Inclusion Criteria:

1. The participant must understand the study procedures and agree to participate by providing written informed consent.
2. The participant must be willing and able to comply with all study procedures and restrictions.
3. The participant must be a Japanese healthy adult male or female, aged 20 to 55 years, inclusive, at the time of informed consent.
4. The participant must have a body mass index (BMI) \>=18.5 and =\<25.0 kg/m\^2 at the Screening Visit.
5. The participant must be a current nonsmoker who has not used tobacco- or nicotine-containing products (eg, nicotine patch) for at least 6 months prior to the first dose of study drug or first invasive procedure.
6. The participant must be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead electrocardiogram, and vital sign measurements performed at the Screening Visit and prior to the first dose of study drug.
7. The participant must meet the following birth control requirements:

   * Is a male participant who is sterile or agrees to use an appropriate method of contraception, including a condom with spermicidal cream or jelly, from the first dose of study drug until 90 days after the last dose of study drug. No restrictions are required for a vasectomized male participant provided the participant is at least 1-year postbilateral vasectomy procedure prior to the first dose of study drug. A male participant whose vasectomy procedure was performed less than 1 year prior to the first dose of study drug must follow the same restrictions as a nonvasectomized man. Appropriate documentation of surgical procedure should be provided.
   * Is a male participant who agrees to not donate sperm from the first dose of study drug until 90 days after the last dose of study drug.
   * Is a female participant of nonchildbearing potential, defined by at least 1 of the following criteria:

     1. Postmenopausal (defined as 12 months of spontaneous amenorrhea in females aged \>45 years or \>=6 months of spontaneous amenorrhea in females aged \>45 years with serum follicle-stimulating hormone \[FSH\] levels \>40 mIU/mL). Appropriate documentation of follicle-stimulating hormone levels should be required.
     2. Hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure.
     3. Had a tubal ligation with appropriate documentation of surgical procedure.
     4. Congenital conditions such as uterine aplasia etc.

Exclusion Criteria:

1. Has a history of clinically significant endocrine, gastrointestinal (including motility disorder and intestinal obstruction), cardiovascular (including arrhythmia), hematological, hepatic, immunological, renal, respiratory, genitourinary, major neurological (including stroke, epileptic seizure), or degenerative ophthalmological abnormalities or diseases
2. Has participated in another investigational trial within 4 weeks or 5 half-lives (whichever is longer) before the pretrial visit (Screening). The 4-week or 5 half-lives window will be derived from the date of the last trial procedure and/or AE related to the trial procedure in the previous trial to the pretrial/Screening Visit of the current trial.
3. Is an employee or immediate family member (eg, spouse, parent, child, sibling) of the sponsor.
4. Has a history of cancer (malignancy).
5. Has any lifetime history of a suicide attempt, or have suicidal ideation or, any suicidal behavior within 12 months, or who are at significant risk to commit suicide, as judged by the investigator using the Columbia Suicide Severity Rating Scale (C-SSRS) or is clinically judged by the investigator to be at risk for suicide.
6. Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food.
7. Has a positive alcohol or drug screen.
8. Had major surgery, donated or lost whole blood prior to the start of study drug administration as any of below:

   For both male and female participants, \>=200 mL within 4 weeks (28 days) For male participants, \>=400 mL within 12 weeks (84 days), \>=800 mL in total within 52 weeks (364 days) For female participants, \>=400 mL within 16 weeks (112 days). \>=400 mL in total within 52 weeks (364 days)
9. Had gastrointestinal surgery that could impact the absorption of study drug.
10. Has a history of a major psychiatric disorder as diagnosed utilizing Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria.
11. Has a known hypersensitivity to any component of the formulation of TAK-935 or related compounds.
12. Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies, beginning approximately 7 days before administration of the initial dose of study drug, throughout the trial (including washout intervals between trial periods), until the Follow-up Visit.
13. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
14. 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.
15. Has a substance abuse disorder.
16. Has a QTcF \>450 msec confirmed with one repeat testing, at the Screening Visit.
17. Had abnormal Screening or Day -1 laboratory values that suggested a clinically significant underlying disease or participant with the following laboratory abnormalities: ALT and/or AST \>1.5 time ULN.
18. Has tested positive for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody, HIV antibody/antigen, or serologic reactions for syphilis at Screening.
19. In the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.

Primary outcomes:
measure: Parts 1 and 2: Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
timeFrame: Part 1: Baseline up to Day 8; Part 2: Baseline up to Day 35
Secondary outcomes:
measure: Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-935
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-935
timeFrame: Days 7, 14, and 21 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-935
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part 1, AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Infinity for TAK-935
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part 1, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for TAK-935
timeFrame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Part 2, AUCtau,ss: Area Under the Plasma Concentration-time Curve During the Dosing Interval at Steady State for TAK-935
timeFrame: Days 7, 14, and 21 pre-dose and at multiple time points (up to 12 hours) post-dose
Other outcomes:
Locations:
city: Shinjuku-ku
country: Japan
facility: Clinical Research Hospital Tokyo
state: Tokyo
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: