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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1177-8044 | Registry Identifier | WHO |
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The purpose of this study is to evaluate the safety and tolerability of single oral doses of TAK-828 in healthy non-Japanese and Japanese participants.
The drug being tested in this study is called TAK-828. TAK-828 is being tested to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single oral doses of TAK-828 in healthy non-Japanese and Japanese participants.
The study enrolled 36 healthy participants. An interleaving crossover design with placebo substitution was used for Cohorts 1 and 2, and a crossover design was used in Cohort 3. Each cohort consisted of 12 participants, and participants were randomized to treatment sequence to receive TAK-828 or placebo after undergoing a fasting stage of at least 8 hours through intervention periods 1-4 for Cohorts 1 and 2 and through intervention periods 1 - 3 for Cohort 3. The assigned treatment sequence will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). An additional interventional period 5 (fed state) is planned to be conducted in either cohort 1 or 2, based on the dose of TAK-828 that will be chosen to be studied under fed conditions. Cohorts 1 and 2 were conducted in non-Japanese participants and Cohort 3 in Japanese participants.
This multi-center trial was conducted in the United States. Participants remained confined to the study site from check-in (Day -1) through Day 4 of each intervention period and returned 7 to 10 days after last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1, Sequence I | Experimental | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 1, Sequence II | Experimental | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 1, Sequence III | Experimental | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-828 | Drug | TAK-828 oral solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. | Day 1 up to 30 days after last dose of study drug (up to 85 days) |
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | Day 1 up to 30 days after last dose of study drug (up to 85 days) | |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose | Hematology and Chemistry values that met the following criteria were considered to be markedly abnormal: Erythrocytes, Hematocrit and Hemoglobin <0.8*Lower Limit of Normal (LLN) or >1.2*Upper Limit of Normal ULN.; Leukocytes <0.5*LLN or >1.5*ULN; Platelet <75 or >600 10^9/liter (L). Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase >3*ULN; Albumin <25 g/L; Bilirubin > 34.2 umol/L; Blood Urea Nitrogen >10.7 mmol/L; Chloride <75 or >126 mmol/L; Creatinine >177 umol/L; Direct Bilirubin >2*ULN; Glucose <2.8 or >19.4 mmol/L; Potassium <3.0 or >6.0 mmol/L; Protein <0.8*LLN or >1.2*ULN; Sodium <130 or >150 mmol/L. | Day 1 up to 7 days after last dose of study drug (up to 52 days) |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Vital signs measurements that met the following criteria were considered to be markedly abnormal: Systolic Blood Pressure (SBP) <85 mmHg or >180 mmHg supine laying face upward) or standing; Diastolic Blood Pressure (DBP) <50 mmHg or >110 mmHg supine or standing; Pulse Rate (PR) <50 beats/minute (bpm) or >120 bpm supine or standing; Temperature <35.6 degrees Celsius (C) or >37.7 degrees C. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828) | Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose | |
| Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828) | Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose |
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Inclusion Criteria: -
Exclusion Criteria: -
1. Has used prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to 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 equal to (<=) 1 gram per day (g/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.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Baltimore | Maryland | United States | ||||
Non-Japanese healthy participants were randomized to Cohort 1 or Cohort 2 with 4 different sequences to receive TAK-828 or placebo in a ratio of 9:3. Japanese healthy participants were randomized into Cohort 3 with 3 different sequences to receive TAK-828 or placebo in a ratio of 8:4.
Participants took part in the study at 2 investigative sites in the United States from 01 March 2016 to 17 June 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1, Sequence I | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| FG001 | Cohort 1, Sequence II | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| FG002 | Cohort 1, Sequence III | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| FG003 | Cohort 1, Sequence IV | Non-Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| FG004 | Cohort 2, Sequence I | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| FG005 | Cohort 2, Sequence II | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| FG006 | Cohort 2, Sequence III | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| FG007 | Cohort 2, Sequence IV | Non-Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. There was a 7-day washout period between each period. Each period lasted 4 days with a 7-day washout period between periods. |
| FG008 | Cohort 3, Sequence I | Japanese participants. TAK-828 15 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
| FG009 | Cohort 3, Sequence II | Japanese participants. TAK-828 15 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 150 mg, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
| FG010 | Cohort 3, Sequence III | Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 150 mg, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1, Sequence I | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. | Safety Set included all participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Day 1 up to 30 days after last dose of study drug (up to 85 days) |
|
From Day 1 up to 30 days after last dose of study drug (up to 85 days).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: Placebo | Non-Japanese participants in Cohort 1 who received placebo-matching TAK-828 oral solution, fasted (after an 8 hour fast), on Day 1 of Periods 1, 2, 3 or 4. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ventricular tachycardia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
Per an audit performed at the study site that enrolled Cohort 3, noncompliance to Good Clinical Practice (GCP) was identified and prevented confirmed reliability of the data collected. Data was still analyzed and results are reported in this posting.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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|
| Cohort 1, Sequence IV | Experimental | Non-Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 2, Sequence I | Experimental | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 2, Sequence II | Experimental | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 2, Sequence III | Experimental | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 2, Sequence IV | Experimental | Non-Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. There was a 7-day washout period between each period. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 3, Sequence I | Experimental | Japanese participants. TAK-828 15 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 3, Sequence II | Experimental | Japanese participants. TAK-828 15 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 150 mg, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Cohort 3, Sequence III | Experimental | Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 150 mg, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
|
| Placebo | Drug | TAK-828 placebo-matching oral solution |
|
| Day 1 up to 7 days after last dose of study drug (up to 52 days) |
| Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose | Heart Rate <50 beats per minute (bpm) >120 bpm; QTcB (Bazett's Correction Formula) ≤50 milliseconds (msec) or ≥500 msec OR ≥30 msec change from Baseline and ≥450 msec; QTcF (Fridericia's Correction Formula) ≤50 msec or ≥500 msec OR ≥30 msec change from Baseline (CFB) and ≥450 msec. | Day 1 up to 7 days after last dose of study drug (up to 52 days) |
| t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828) | Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose |
| AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828) | Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose |
| Austin |
| Texas |
| United States |
| Lost to Follow-up |
|
| Voluntary Withdrawal |
|
| Other Reason Not Specified |
|
| BG001 | Cohort 1, Sequence II | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| BG002 | Cohort 1, Sequence III | Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| BG003 | Cohort 1, Sequence IV | Non-Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| BG004 | Cohort 2, Sequence I | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| BG005 | Cohort 2, Sequence II | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| BG006 | Cohort 2, Sequence III | Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods. |
| BG007 | Cohort 2, Sequence IV | Non-Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. There was a 7-day washout period between each period. Each period lasted 4 days with a 7-day washout period between periods. |
| BG008 | Cohort 3, Sequence I | Japanese participants. TAK-828 15 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
| BG009 | Cohort 3, Sequence II | Japanese participants. TAK-828 15 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 150 mg, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
| BG010 | Cohort 3, Sequence III | Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 150 mg, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods. |
| BG011 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Smoking Classification | Number | participants |
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| Alcohol Classification | Number | participants |
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| Xanthine/Caffeine Consumption | Number | participants |
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| Female Reproductive Status | Number | participants |
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| OG001 |
| Cohort 1: TAK-828 0.1 mg/ Fasted |
Non-Japanese participants in Cohort 1 who received TAK-828 0.1 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1. |
| OG002 | Cohort 1: TAK-828 0.5 mg/ Fasted | Non-Japanese participants in Cohort 1 who received TAK-828 0.5 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 2. |
| OG003 | Cohort 1: TAK-828 15 mg/ Fasted | Non-Japanese participants in Cohort 1 who received TAK-828 15 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 3. |
| OG004 | Cohort 1: TAK-828 100 mg/ Fasted | Non-Japanese participants in Cohort 1 who received TAK-828 100 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 4. |
| OG005 | Cohort 1: TAK-828 100 mg/ Fed | Non-Japanese participants in Cohort 1 who received TAK-828 100 mg oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. |
| OG006 | Cohort 2: Placebo | Non-Japanese participants in Cohort 2 who received placebo-matching TAK-828 oral solution, fasted (after an 8 hour fast), on Day 1 of Periods 1, 2, 3 or 4. |
| OG007 | Cohort 2: TAK-828 3 mg/ Fasted | Non-Japanese participants in Cohort 2 who received TAK-828 3 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1. |
| OG008 | Cohort 2: TAK-828 50 mg/ Fasted | Non-Japanese participants in Cohort 2 who received TAK-828 50 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 2. |
| OG009 | Cohort 2: TAK-828 200 mg/ Fasted | Non-Japanese participants in Cohort 2 who received TAK-828 200 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 3. |
| OG010 | Cohort 2: TAK-828 100 mg/ Fasted | Non-Japanese participants in Cohort 2 who received TAK-828 100 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 4. |
| OG011 | Cohort 2: TAK-828 100 mg/ Fed | Non-Japanese participants in Cohort 2 who received TAK-828 100 mg oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. |
| OG012 | Cohort 3: Placebo | Japanese participants in Cohort 3 who received placebo-matching TAK-828 oral solution, fasted (after an 8 hour fast), on Day 1 of Periods 1, 2 or 3. |
| OG013 | Cohort 3: TAK-828 15 mg/ Fasted | Japanese participants in Cohort 3 who received TAK-828 15 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1. |
| OG014 | Cohort 3: TAK-828 100 mg/ Fasted | Japanese participants in Cohort 3 who received TAK-828 100 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 2. |
| OG015 | Cohort 3: TAK-828 150 mg/ Fasted | Japanese participants in Cohort 3 who received TAK-828 150 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 3. |
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| Secondary | Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828) | Pharmacokinetic (PK) Set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma or urine concentration of TAK-828F. Food effect statistical analysis is based on 10 participants who received TAK-828 100 mg under fasted and fed conditions. | Posted | Mean | Standard Deviation | ng/mL | Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose |
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| Primary | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) | Safety Set included all participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Day 1 up to 30 days after last dose of study drug (up to 85 days) |
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| Primary | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose | Hematology and Chemistry values that met the following criteria were considered to be markedly abnormal: Erythrocytes, Hematocrit and Hemoglobin <0.8*Lower Limit of Normal (LLN) or >1.2*Upper Limit of Normal ULN.; Leukocytes <0.5*LLN or >1.5*ULN; Platelet <75 or >600 10^9/liter (L). Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase >3*ULN; Albumin <25 g/L; Bilirubin > 34.2 umol/L; Blood Urea Nitrogen >10.7 mmol/L; Chloride <75 or >126 mmol/L; Creatinine >177 umol/L; Direct Bilirubin >2*ULN; Glucose <2.8 or >19.4 mmol/L; Potassium <3.0 or >6.0 mmol/L; Protein <0.8*LLN or >1.2*ULN; Sodium <130 or >150 mmol/L. | Safety Set included all participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Day 1 up to 7 days after last dose of study drug (up to 52 days) |
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| Primary | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose | Vital signs measurements that met the following criteria were considered to be markedly abnormal: Systolic Blood Pressure (SBP) <85 mmHg or >180 mmHg supine laying face upward) or standing; Diastolic Blood Pressure (DBP) <50 mmHg or >110 mmHg supine or standing; Pulse Rate (PR) <50 beats/minute (bpm) or >120 bpm supine or standing; Temperature <35.6 degrees Celsius (C) or >37.7 degrees C. | Safety Set included all participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Day 1 up to 7 days after last dose of study drug (up to 52 days) |
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| Primary | Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose | Heart Rate <50 beats per minute (bpm) >120 bpm; QTcB (Bazett's Correction Formula) ≤50 milliseconds (msec) or ≥500 msec OR ≥30 msec change from Baseline and ≥450 msec; QTcF (Fridericia's Correction Formula) ≤50 msec or ≥500 msec OR ≥30 msec change from Baseline (CFB) and ≥450 msec. | Safety Set included all participants who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Day 1 up to 7 days after last dose of study drug (up to 52 days) |
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| Secondary | Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828) | Pharmacokinetic (PK) Set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma or urine concentration of TAK-828F. | Posted | Median | Full Range | hours (h) | Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose |
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| Secondary | t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828) | Pharmacokinetic (PK) Set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma or urine concentration of TAK-828F. T1/2z was not calculated for the TAK-828 0.1 mg arm because Lambda z, required for the calculation, was not calculated due to the lack of a well-defined terminal elimination phase. | Posted | Mean | Standard Deviation | h | Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose |
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| Secondary | AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828) | PK Set included participants who received at least 1 dose of study drug and had at least 1 measurable plasma or urine concentration of TAK-828F.Food effect statistical analysis is based on 10 participants who received TAK-828 100 mg fasted and fed.AUC∞ was not calculated for TAK-828 0.1 mg arm due to lack of well-defined terminal elimination phase. | Posted | Mean | Standard Deviation | ng*h/mL | Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose |
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| 0 |
| 10 |
| 3 |
| 10 |
| EG001 | Cohort 1: TAK-828 0.1 mg/ Fasted | Non-Japanese participants in Cohort 1 who received TAK-828 0.1 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1. | 1 | 9 | 5 | 9 |
| EG002 | Cohort 1: TAK-828 0.5 mg/ Fasted | Non-Japanese participants in Cohort 1 who received TAK-828 0.5 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 2. | 0 | 8 | 3 | 8 |
| EG003 | Cohort 1: TAK-828 15 mg/ Fasted | Non-Japanese participants in Cohort 1 who received TAK-828 15 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 3. | 0 | 7 | 1 | 7 |
| EG004 | Cohort 1: TAK-828 100 mg/ Fasted | Non-Japanese participants in Cohort 1 who received TAK-828 100 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 4. | 0 | 7 | 0 | 7 |
| EG005 | Cohort 1: TAK-828 100 mg/ Fed | Non-Japanese participants in Cohort 1 who received TAK-828 100 mg oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. | 0 | 8 | 1 | 8 |
| EG006 | Cohort 2: Placebo | Non-Japanese participants in Cohort 2 who received placebo-matching TAK-828 oral solution, fasted (after an 8 hour fast), on Day 1 of Periods 1, 2, 3 or 4. | 0 | 9 | 0 | 9 |
| EG007 | Cohort 2: TAK-828 3 mg/ Fasted | Non-Japanese participants in Cohort 2 who received TAK-828 3 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1. | 0 | 9 | 1 | 9 |
| EG008 | Cohort 2: TAK-828 50 mg/ Fasted | Non-Japanese participants in Cohort 2 who received TAK-828 50 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 2. | 0 | 9 | 1 | 9 |
| EG009 | Cohort 2: TAK-828 200 mg/ Fasted | Cohort 2: TAK-828 200 mg/ Fasted Non-Japanese participants in Cohort 2 who received TAK-828 200 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 3. | 0 | 9 | 1 | 9 |
| EG010 | Cohort 2: TAK-828 100 mg/ Fasted | Non-Japanese participants in Cohort 2 who received TAK-828 100 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 4. | 0 | 9 | 2 | 9 |
| EG011 | Cohort 2: TAK-828 100 mg/ Fed | Non-Japanese participants in Cohort 2 who received TAK-828 100 mg oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. | 0 | 4 | 0 | 4 |
| EG012 | Cohort 3: Placebo | Japanese participants in Cohort 3 who received placebo-matching TAK-828 oral solution, fasted (after an 8 hour fast), on Day 1 of Periods 1, 2 or 3. | 0 | 12 | 0 | 12 |
| EG013 | Cohort 3: TAK-828 15 mg/ Fasted | Japanese participants in Cohort 3 who received TAK-828 15 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1. | 0 | 8 | 2 | 8 |
| EG014 | Cohort 3: TAK-828 100 mg/ Fasted | Japanese participants in Cohort 3 who received TAK-828 100 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 2. | 0 | 8 | 6 | 8 |
| EG015 | Cohort 3: TAK-828 150 mg/ Fasted | Japanese participants in Cohort 3 who received TAK-828 150 mg oral solution, fasted (after an 8 hour fast), on Day 1 of Period 3. | 0 | 6 | 4 | 6 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Feeling abnormal | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
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| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Temporomandibular joint syndrome | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Chromaturia | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
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| Foreign body reaction | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Bioequivalence interval of 0.80 to 1.25 |
| SBP <85 mmHg: standing, after 3 minutes |
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| DBP <50 mmHg: supine, after 5 minutes |
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| DBP <50 mmHg: standing, after 3 minutes |
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| PR <50 bpm: supine, after 5 minutes |
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| PR <50 bpm: standing, after 1 minute |
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| PR >120 bpm: standing, after 1 minute |
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| PR <50 bpm: standing, after 3 minutes |
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| PR >120 bpm: standing, after 3 minutes |
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| Temperature: <35.6 C |
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| QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec |
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Bioequivalence interval of 0.80 to 1.25 |