Phase 1 TAK-906 Single and Multiple Ascending Dose Study in Japanese Healthy Male Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Japanese Healthy Adult Male Participants
• Intervention / Treatment: Drug: TAK-906; Drug: TAK-906 Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Toshima, Tokyo, Japan
      • Sekino Clinical Pharmacology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-906 50 mg; Cohort 1; TAK-906 50 milligram (mg) capsules, orally, once daily on Day 1 as Single Dose Period followed by TAK-906 50 mg capsules, orally, twice daily from Day 3 to 7 as Multiple Dose Period.	Drug: TAK-906; TAK-906 capsules.
Placebo Comparator: TAK-906 Placebo; Cohort 1; TAK-906 Placebo capsules, orally, once daily on Day 1 as Single Dose Period followed by TAK-906 Placebo capsules, orally, twice daily from Day 3 to 7 as Multiple Dose Period.	Drug: TAK-906 Placebo; Placebo capsules.
Experimental: TAK-906 100 mg; Cohort 2; TAK-906 100 mg capsules, orally, once daily on Day 1 as Single Dose Period followed by TAK-906 100 mg capsules, orally, twice daily from Day 3 to 7 as Multiple Dose Period. Cohort 2 will be conducted after Cohort 1.	Drug: TAK-906; TAK-906 capsules.
Placebo Comparator: TAK-906 Placebo; Cohort 2; TAK-906 Placebo capsules, orally, once daily on Day 1 as Single Dose Period followed by TAK-906 Placebo capsules, orally, twice daily from Day 3 to 7 as Multiple Dose Period. Cohort 2 will be conducted after Cohort 1.	Drug: TAK-906 Placebo; Placebo capsules.
Experimental: TAK-906 10 mg; Cohort 3; TAK-906 10 mg capsules, orally, once daily on Day 1 as Single Dose Period followed by TAK-906 10 mg capsules, orally, twice daily from Day 3 to 7 as Multiple Dose Period.	Drug: TAK-906; TAK-906 capsules.
Placebo Comparator: TAK-906 Placebo; Cohort 3; TAK-906 Placebo capsules, orally, once daily on Day 1 as Single Dose Period followed by TAK-906 Placebo capsules, orally, twice daily from Day 3 to 7 as Multiple Dose Period.	Drug: TAK-906 Placebo; Placebo capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience at Least One Treatment-Emergent Adverse Event (TEAE)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with the treatment or study participation. A treatment-emergent adverse events (TEAE) is defined as an AE whose date of onset occurs on or after the start of study drug.	Baseline up to Day 14
Number of Participants With Markedly Abnormal Values of Vital Signs	Reported data were numbers of participants who met markedly abnormal criteria of vital signs. Vital signs included body temperature, respiratory rate, blood pressure, and pulse. Vital signs collected were classified as markedly abnormal values if they met the following criteria: systolic blood pressure less than (<) 85 millimeter of mercury (mmHg) or greater than (>) 180 mmHg, diastolic blood pressure <50 mmHg or >110 mmHg, pulse <50 beats per minute (bpm) or >120 bpm, body temperature <35.6 °C or >37.7 °C.	Baseline up to Day 14
Number of Participants With Markedly Abnormal Values of Clinical Laboratory Test Results	Reported data were numbers of participants who met markedly abnormal criteria of clinical laboratory test results. Clinical laboratory test results collected were classified as markedly abnormal values if they met the following criteria: red blood cells <0.8×lower limit of normal (LLN) or >1.2×upper limit of normal (ULN), platelets <75×10^3/μL or >600×10^3/μL, white blood cells <0.5×LLN or >1.5×ULN, protein (total) <0.8×LLN or >1.2×ULN, albumin <2.5 g/dL, blood urea nitrogen >30 mg/dL, uric acid >13.0 mg/dL, creatinine >2.0 mg/dL, total cholesterol >300 mg/dL, triglycerides >2.5×ULN, bilirubin (total) >2.0 mg/dL, Sodium <130 mEq/L or >150 mEq/L, Potassium <3.0 mEq/L or >6.0 mEq/L, Chloride <75 mEq/L or >126 mEq/L, Calcium <7.0 mg/dL or >11.5 mg/dL, Phosphorus <1.6 mg/dL or >6.2 mg/dL, alkaline phosphatase >3×ULN, aspartate aminotransferase >3×ULN, alanine aminotransferase >3×ULN, gamma-glutamyl transferase >3×ULN, glucose <50 mg/dL or >350 mg/dL, Magnesium <1.2 mg/dL or >3.0 mg/dL.	Baseline up to Day 14
Number of Participants With Markedly Abnormal Values of 12-lead Electrocardiogram (ECG)	Reported data were numbers of participants who met markedly abnormal criteria of 12-lead ECG. A standard 12-lead ECG was performed. The data collected was classified as markedly abnormal values if it met the following criteria: heart rate <50 bpm or >120 bpm, QT interval less than or equal to (<=) 50 msec or greater than or equal to (>=) 460 msec, QTcF interval <=50 msec or either of the following conditions was met: observed value >=500 msec, change from Day 1 Predose >= 30 msec and observed value >=450 msec.	Baseline up to Day 8
Number of Participants With TEAEs Related to Physical Examinations	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with the treatment or study participation. A treatment-emergent adverse events (TEAE) is defined as an AE whose date of onset occurs on or after the start of study drug.	Baseline up to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	AUC∞ is a measure of total plasma exposure to TAK-906 and its Metabolite M23 from Time 0 extrapolated to infinity, calculated using the observed value of the last quantifiable concentration.	Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period	Cmax is the peak plasma concentration of TAK-906 and its metabolite M23.	Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
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	AUCtau is a measure of total plasma exposure to TAK-906 and its Metabolite M23 from Time 0 to Time tau over the dosing interval.	Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period	Tmax is time to reach the peak plasma concentration of TAK-906 and its metabolite M23.	Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
t1/2z: Terminal Disposition Phase Half-life for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period	t1/2z is time for the plasma concentration of TAK-906 and its metabolite M23 to decrease by half.	Day 1 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
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	Ae(0-24) is the amount of TAK-906 and its metabolite M23 excreted in urine from Time 0 to 24 Hours postdose.	Day 1 pre-dose and 0-6, 6-12, and 12-24 hours post-dose
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	Fe24 was calculated as percentage of administered dose of drug excreted in urine from Time 0 to 24 Hours for TAK-906 and its metabolite M23.	Time Frame Day 1 pre-dose and 0-6, 6-12, and 12-24 hours post-dose
CLR: Renal Clearance for TAK-906 and Its Metabolite M23 on Day 1 of Single Dose Period	Renal clearance is a measure of apparent clearance of TAK-906 and its metabolite M23 from the urine.	Day 1 pre-dose and 0-6, 6-12, and 12-24 hours post-dose
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	AUC(τ,ss) is a measure of total plasma exposure to TAK-906 and its metabolite M23 from Time 0 during dosing interval at steady state.	Day 7 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
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	Cmax, ss is the peak plasma concentration of TAK-906 and its metabolite M23 during dosing interval at steady state.	Day 7 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
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	Tmax,ss is defined as time to reach the peak plasma concentration at steady state for TAK-906 and its metabolite M23.	Day 7 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
t1/2z: Terminal Disposition Phase Half-life for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period	t1/2z is time for the plasma concentration of TAK-906 and its metabolite M23 to decrease by half.	Day 7 pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose
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	Aetau is the amount of TAK-906 and its metabolite M23 excreted in urine during a dosing Interval.	Day 7 pre-dose and 0-6 and 6-12 hours post-dose
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	Fetau was calculated as percentage 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.	Day 7 pre-dose and 0-6 and 6-12 hours post-dose
CLR: Renal Clearance for TAK-906 and Its Metabolite M23 on Day 7 of Multiple Dose Period	Renal clearance is a measure of apparent clearance of TAK-906 and its metabolite M23 from the urine.	Day 7 pre-dose and 0-6 and 6-12 hours post-dose
AUCtau: Area Under the Serum Concentration-time Curve During a Dosing Interval for Serum Prolactin on Day 1 of Single Dose Period	AUCtau defined as area under the serum concentration-time curve during a dosing interval for serum prolactin was calculated.	Day 1 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Cmax: Maximum Observed Serum Concentration for Serum Prolactin on Day 1 of Single Dose Period	Cmax is the peak serum concentration of serum prolactin.	Day 1 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
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	AUClast defined as area under the serum concentration-time curve from Time 0 to the Time of the last quantifiable concentration for serum prolactin was calculated.	Day 1 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
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	AUC(t,ss) defined as area under the serum concentration-time curve from Time 0 during dosing interval at steady state for serum prolactin was calculated.	Day 7 pre-dose and 1, 2, 4, 6, and 24 hours post-dose
Cmax,ss: Maximum Observed Serum Concentration During Dosing Interval at Steady State for Serum Prolactin on Day 7 of Multiple Dose Period	Cmax,ss is the peak serum concentration of serum prolactin during dosing interval at steady state.	Day 7 pre-dose and 1, 2, 4, 6, and 24 hours post-dose

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2017
• Primary Completion (Actual): October 7, 2017
• Study Completion (Actual): October 7, 2017

Study Registration Dates

• First Submitted: July 31, 2017
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (Actual): August 2, 2017

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: December 18, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Drug therapy
• Other Study ID Numbers: TAK-906-1004; U1111-1197-9663 (Registry Identifier: WHO); JapicCTI-173661 (Registry Identifier: JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes