Clinical trial NCT03687684: Phase 1 Study of TAK-831 in Healthy Adult Asian Subjects
Official title: Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of TAK 831 in Healthy Adult Asian Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2018-09-27
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-831 when administered as single or multiple oral doses in healthy adult Asian participants.

Detailed description: The drug being tested in this study is called TAK-831. This study will assess the safety, tolerability, pharmacokinetics (PK), and Pharmacodynamics (PD) of TAK-831 when administered as single or multiple oral doses in healthy adult Asian participants (Japanese and Chinese participants).

The study will enroll approximately 40 participants and include up to 5 cohorts of healthy adult Japanese or Chinese participants as following (8 participants per a cohort). Cohorts 3, 4 and 5 are optional and will be decided to run based on the data of Cohorts 1 and 2. Dose level for these cohorts will be defined based on the result of Cohort 1 or Cohort 2.

* Japanese Cohort 1-A; TAK-831 100 mg single dose + TAK-831 300 mg single dose
* Japanese Cohort 1-B; TAK-831 100 mg single dose + Placebo single dose
* Japanese Cohort 1-C; Placebo single dose + TAK-831 300 mg single dose
* Japanese Cohort 2; TAK-831 300 mg or TAK-831 matching placebo, single dose + TAK-831 300 mg or TAK-831 matching placebo, multiple dose \*
* Chinese Cohort 3; TAK-831 600 mg or TAK-831 matching placebo, single dose + TAK-831 600 mg or TAK-831 matching placebo, multiple dose
* Japanese Cohort 4; TAK-831 600 mg or TAK-831 matching placebo, single dose + TAK-831 600 mg or TAK-831 matching placebo, multiple dose
* Japanese Cohort 5; TAK-831 50 mg or TAK-831 matching placebo, single dose + TAK-831 50 mg or TAK-831 matching placebo, multiple dose \*The dose in Cohort 2 will be adjusted based on the safety and tolerability as well as PK and PD in Cohort 1.

Above all treatment, randomization information will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need) and TAK-831 will be administered orally.

This single center trial will be conducted in Japan. The overall time to participate in Cohort 1 of this study is approximately 12 days and 19 days in Cohorts 2 to 5. 11 days (for Cohort 1) or 12 days (for Cohorts 2 to 5) after last dose of study drug, participants will be contacted by telephone for a follow-up assessment unless abnormal, clinically significant findings are observed upon discharge.

Eligibility criteria: Inclusion Criteria:

1. The participant must understand the study procedures and agree to participate by providing written informed consent (for Chinese participants, an interpreter should be present as necessary).
2. The participant must be willing and able to comply with all study procedures and restrictions.
3. The participant must be male or female (of nonchildbearing potential) aged 20 to 55 years, inclusive, at the Screening.
4. The participant must have a body mass index (BMI) \>=18.5 kg/m\^2 and =\<25.0 kg/m\^2 at the Screening.
5. The participant must be a current nonsmoker who has not used tobacco- or nicotine-containing products (e.g., nicotine patch) for at least 6 months prior to the Screening.
6. Chinese participants are defined as participants who were born in mainland China, and their biological parents and grandparents must all have been of Chinese origin (for Cohort 3 only).
7. Chinese participants who have lived out of China for more than 5 years must not have significantly modified their diets since leaving China (for Cohort 3 only).
8. The participant must be judged to be in good health by the investigator, based on clinical evaluations including laboratory tests, medical history, full physical examination, 12-lead electrocardiogram, and vital sign measurements performed at the Screening and prior to the first dose of study drug.
9. The participant must meet the birth control requirements.

Exclusion Criteria:

1. The participant has a history of clinically significant endocrine, gastrointestinal (including motility disorder and intestinal obstruction), cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary, or presents with major neurological (including stroke and chronic seizures) abnormalities or diseases.
2. The participant has participated in another investigational trial within 4 weeks before the pretrial visit (Screening). The 4-week window will be derived from the date of the last trial procedure and/or adverse event (AE) related to the trial procedure in the previous trial to the Screening Visit of the current trial.
3. The participant is an employee or immediate family member (e.g., spouse, parent, child, sibling) of the sponsor.
4. The participant has a history of cancer (malignancy).
5. The participant has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food.
6. The participant has a positive alcohol or drug or immunological screen.
7. The participant is of childbearing potential or lactating.
8. The participant had major surgery, received or lost 1 unit of blood (approximately 500 milliliters \[mL\]) within 8 weeks prior to the first dose of study drug.
9. The participant with any gastrointestinal (GI) surgery that could impact upon the absorption of study drug.
10. The participant has a known hypersensitivity to any component of the formulation of TAK-831 or related compounds.
11. The participant 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 trial drug, throughout the trial (including washout intervals between trial periods), until the Follow-up Visit.
12. The participant has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\] per day).
13. The participant who 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.
14. The participant has a history of drug abuse.
15. The participant has a (QT interval with Fridericia's correction method) QTcF \>450 milliseconds (msec) (males) or \>470 msec (females) or PR outside the range of 120 to 220 msec at the Screening Visit or Check-in.

Primary outcomes:
measure: Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE)
timeFrame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
measure: Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results
timeFrame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
measure: Number of Participants Reporting at Least One TEAE Related to Vital Sign
timeFrame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
measure: Number of Participants Reporting at Least One TEAE Related to Body Weight
timeFrame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
measure: Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters
timeFrame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK-831
timeFrame: Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose
measure: Cohorts 2 to 5, Cmax, ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831
timeFrame: Day 17 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831
timeFrame: Cohort 1: Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72 hours post-dose; Day 17 pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post-dose
measure: AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831
timeFrame: Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831
timeFrame: Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose
measure: Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831
timeFrame: Day 1: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose and Day 17: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose
Other outcomes:
Locations:
city: Shinjuku-ku
country: Japan
facility: Clinical Research Hospital Tokyo
state: Tokyo
Study officials:
References: