Clinical trial NCT03237156: Phase 1 TAK-906 Single and Multiple Ascending Dose Study in Japanese Healthy Male Participants
Official title: A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-906 in Japanese Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Japanese Healthy Adult Male Participants
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-08-02
Enrollment: 24
Sex: MALE
Minimum age (years): 20
Maximum age (years): 60
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 safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of TAK-906 in Japanese healthy male participants.

Detailed description: The drug being tested in this study is called TAK-906. TAK-906 is being tested in healthy participants in order to evaluate safety and tolerability of single and multiple oral doses of TAK-906 in Japanese healthy male participants.

The study will enroll approximately 24 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in Cohort 1 or Cohort 3. Study drug will be administered in a double-blind manner which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need), orally, once daily on Day 1 as Single Dose Period and twice daily from Day 3 to 7 as Multiple Dose Period:

* TAK-906 50 mg (Cohort 1)
* TAK-906 100 mg (Cohort 2)
* TAK-906 10 mg (Cohort 3)
* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

Cohort 2 will be conducted after the completion of Cohort 1. This will be conducted in Japan.

Eligibility criteria: Inclusion Criteria:

1. In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
3. The participant is a Japanese healthy adult male, aged 20 to 60 years, inclusive, at the time of informed consent.
4. The participant weighs at least 50 kilogram (kg) and has a body mass index (BMI) from 18.5 to 25 kilogram per square meter (kg/m\^2), inclusive at Screening.
5. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from the signing of informed consent to 12 weeks (84 days) after the last dose of study drug. The female partner of a male participant should also be advised to use adequate contraception.

Exclusion Criteria:

1. The participant has received any investigational compound within 16 weeks (112 days) prior to the first dose of study drug.
2. The participant has received TAK-906 in a previous clinical study or as a therapeutic agent.
3. The participant is an immediate family member of or an investigational site employee, or is in a dependent relationship with an investigational 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 uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality, which may impact the ability of the participant to participate in the study or potentially confound its results.
5. The participant has a history of any psychiatric disease that would interfere with the evaluation of study drug activity (prolactin concentration) or safety.
6. The participant has a history of seizure or tardive dyskinesia.
7. The participant has a history of hyperprolactinemia, pituitary adenoma, and/or hypothyroidism.
8. The participant has a family history of prolonged QT.
9. The participant has undergone previous gastric bypass surgery or currently had a gastric band fitted.
10. The participant has dysphagia and/or inability to swallow study medication whole.
11. The participant has a known hypersensitivity to any component of the TAK-906 formulation or related compounds.
12. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the Screening visit, or is unwilling to agree to abstain from alcohol and drugs throughout the study, or has a positive urine test result for drugs of abuse or a positive alcohol screen (urine alcohol test/breath test) result for alcohol at Screening.
13. The participant has taken any excluded medication, supplements, or dietary products during the time periods listed in the Excluded Medications, Supplements, and Dietary Products table.
14. If male, the participant intends to donate sperm during the course of this study or for at least 12 weeks (84 days) after the last dose of study drug.
15. The participant has current or recent (within 24 weeks \[168 days\]) gastrointestinal disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention).
16. The participant has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1.
17. The participant has a positive test result for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, or serological reactions for syphilis at Screening.
18. The participant has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 4 weeks (28 days) prior to the first dose of study drug. Cotinine test is positive at Screening.
19. The participant has poor peripheral venous access.
20. The participant has undergone whole blood collection of at least 200 mL within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the start of study drug administration.
21. The participant has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the start of study drug administration.
22. The participant has undergone blood component collection within 2 weeks (14 days) prior to the start of study drug administration.
23. The participant has a Screening or Check-in (Day -1) electrocardiogram (ECG) that was abnormal (clinically significant).
24. The participant has a QTcF of greater than (\>) 450 millisecond (msec) on the ECG at Screening, at Check-in (Day -1), or prior to the first dose of study drug (Day 1 predose).
25. The participant has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or any participant with the following lab abnormalities:

    * Transaminase (alanine aminotransferase \[ALT\] and/or aspartate aminotransferase \[AST\]) and/or total bilirubin \>1.5 × upper limit of normal (ULN).
    * Creatinine \>1.2 milligram per deciliter (mg/dL).
26. The participant who, in the opinion of the investigator or sub-investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.

Primary outcomes:
measure: Number of Participants Who Experience at Least One Treatment-Emergent Adverse Event (TEAE)
timeFrame: Baseline up to Day 14
measure: Number of Participants With Markedly Abnormal Values of Vital Signs
timeFrame: Baseline up to Day 14
measure: Number of Participants With Markedly Abnormal Values of Clinical Laboratory Test Results
timeFrame: Baseline up to Day 14
measure: Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG)
timeFrame: Baseline up to Day 8
measure: Number of Participants With TEAEs Related to Physical Examinations
timeFrame: Baseline up to Day 14
Secondary outcomes:
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: Cmax: Maximum Observed Plasma Concentration for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: t1/2z: Terminal Disposition Phase Half-life for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours Postdose for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 0-6, 6-12, and 12-24 hours post-dose
measure: Fe24: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to 24 Hours for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose
timeFrame: Time Frame Day 1 pre-dose and 0-6, 6-12, and 12-24 hours post-dose
measure: CLR: Renal Clearance for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 0-6, 6-12, and 12-24 hours post-dose
measure: AUC(τ,ss): Area Under the Plasma Concentration-time Curve From Time 0 During Dosing Interval at Steady State for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: Cmax,ss: Maximum Observed Plasma Concentration During Dosing Interval at Steady State for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: Tmax,ss: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: t1/2z: Terminal Disposition Phase Half-life for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
measure: Aetau: Amount of Drug Excreted in Urine During a Dosing Interval for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 0-6 and 6-12 hours post-dose
measure: Fetau: Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time Tau Over the Dosing Interval for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 0-6 and 6-12 hours post-dose
measure: CLR: Renal Clearance for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 0-6 and 6-12 hours post-dose
measure: AUCtau: Area Under the Serum Concentration-time Curve During a Dosing Interval for Serum Prolactin on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
measure: Cmax: Maximum Observed Serum Concentration for Serum Prolactin on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
measure: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Serum Prolactin on Day 1 of Single Dose Period
timeFrame: Day 1 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
measure: AUC(t,ss): Area Under the Serum Concentration-time Curve From Time 0 During Dosing Interval at Steady State for Serum Prolactin on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
measure: Cmax,ss: Maximum Observed Serum Concentration During Dosing Interval at Steady State for Serum Prolactin on Day 7 of Multiple Dose Period
timeFrame: Day 7 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Other outcomes:
Locations:
city: Toshima
country: Japan
facility: Sekino Clinical Pharmacology Clinic
state: Tokyo
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: