Clinical trial NCT02817516: A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of TAK-828 Escalating Multiple-Doses in Healthy Participants
Official title: A Randomized, Double-Blind (Sponsor-Open), Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Multiple Doses of TAK-828 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-06-29
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the safety and tolerability of multiple oral doses of TAK-828 in healthy participants.

Detailed description: The drug being tested in this study is called TAK-828. TAK-828 is being tested to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics in healthy non-Japanese and Japanese participants in Parts 1 and 2, respectively.

The study will enroll approximately 56 participants. Participants will be randomly assigned (by chance, like flipping a coin) to receive either TAK-828 or matching placebo. This assignment will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

Proposed doses:

* Part 1: TAK-828 15 mg, 45 mg, 75 mg, 100 mg, and placebo twice daily
* Part 2: TAK-828 45 mg, and 100 mg, and placebo twice daily

All participants will be asked to take the solution at the same time each day throughout the study.

This multi-center trial will be conducted in the United States.

Eligibility criteria: Inclusion:

For Parts 1 and 2, participant eligibility is determined according to the following criteria prior to entry into the study:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative, signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.
3. The participant is a healthy male, or a healthy female not of child-bearing potential. Females not of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (example, defined as at least 1 year since last regular menses, with a follicle-stimulating hormone \[FSH\] level of greater than (\>) 40 international units per liter \[IU/L\] or at least 5 years since last regular menses confirmed before any study drug is administered).
4. For Part 1: the participant is a non-Japanese adult, aged 18 to 55 years (inclusive) at the time of informed consent and first dose of study drug.
5. For Part 1: the participant weighs at least 50 kilogram (kg) and has a body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m\^2) (inclusive) at Screening.
6. For Part 2: the participant is of Japanese descent (born to Japanese parents and grandparents), aged 20 to 55 years (inclusive) at the time of informed consent and first dose of study drug.
7. For Part 2: the participant weighs at least 45 kg and has a BMI of 18.5 to 25 kg/m\^2 (inclusive) at Screening.

Exclusion Criteria

For Parts 1 and 2, any participant who meets any of the following criteria will not qualify for entry into the study:

1. The participant received any investigational compound within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug.
2. The participant used prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) before Check-in (Day -1). Herbal supplements and hormone replacement therapy (HRT) must be discontinued 28 days prior to Check-in (Day -1). As an exception, acetaminophen may be used at doses of less than or equal to (\<=) 1 gram/day. Limited use of nonprescription medications that are not believed to affect participant safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.
3. The participant is an immediate family member or study-site employee or is in a dependent relationship with a study-site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
4. The participant has a history or presence of any disease or condition (or there is any finding upon review of the participant's medical history, physical examination, or clinical laboratory tests giving reasonable suspicion of a disease) that could interfere with study participation or safety, contraindicate taking TAK-828 or a similar drug in the same class, or potentially confound the study results (example, history or presence of clinically significant neurologic, cardiovascular, pulmonary, hepatic, hematologic, renal, immunologic, metabolic, musculoskeletal, gastrointestinal, endocrine, or psychiatric disease). It is the responsibility of the investigator to assess the clinical significance; however, consultation with the Takeda medical monitor may be warranted.
5. The participant has a known hypersensitivity to any component of the formulation of TAK-828.
6. The participant has an active infection at Screening.
7. The participant has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in (Day -1).
8. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year, or the participant drinks 7 or more drinks/week for females or 14 or more drinks/week for males (1 drink=5 ounces \[150 milliliter {mL}\] of wine, 12 ounces \[360 mL\] of beer, or 1.5 ounces \[45 mL\] of hard liquor) within 6 months before the Screening visit or is unwilling to abstain from alcohol and drugs throughout the study.
9. The participant is taking or took any excluded medication, supplements, or food products during the time periods listed in the Prohibited Medications, Foods, and Products table
10. If male, the participant intends to donate sperm during the course of this study or for 14 weeks after the last dose of study drug.
11. The participant has any condition possibly affecting drug absorption (example, gastrectomy).
12. The participant has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years before Screening.
13. The participant has a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at Screening or has a known history of human immunodeficiency virus (HIV) infection.
14. The participant used nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 28 days prior to Check-in (Day -1) or cotinine test is positive at Screening or Check-in (Day -1).
15. The participant has poor peripheral venous access.
16. The participant donated or lost 450 mL or more of his or her blood volume (including plasmapheresis) or had a transfusion of any blood product within 30 days prior to Day 1.
17. The participant has a Screening or Check-in (Day -1) abnormal (clinically significant) ECG. Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature of the principal investigator or medically qualified subinvestigator.
18. The participant has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or the participant has the following laboratory abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 3 times the upper limit of normal (ULN).
19. The participant has a creatine kinase isoenzyme MB (CK-MB) or cardiac troponin above the ULN at Screening or Day -1.
20. If female, the participant is of childbearing potential (example, premenopausal, not sterilized).

Primary outcomes:
measure: Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
timeFrame: Baseline up to 10 days after last dose of study drug (Day 24)
measure: Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE)
timeFrame: Baseline up to 10 days after last dose of study drug (Day 24)
measure: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose
timeFrame: Baseline up to 10 days after last dose of study drug (Day 24)
measure: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
timeFrame: Baseline up to 10 days after last dose of study drug (Day 24)
measure: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) at Least Once Post-dose
timeFrame: Baseline up to 10 days after last dose of study drug (Day 24)
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Free Base of TAK-828 (TAK-828F)
timeFrame: Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-828F
timeFrame: Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-828F
timeFrame: Cohorts 1 and 2: Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohort 3: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Other outcomes:
Locations:
city: Austin
country: United States
state: Texas
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: