Dose Finding StudyPhase 1NCT02706834

Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of TAK-828 in Healthy Participants

A Phase 1 study testing TAK-828 in people with Dose Finding Study, run by Takeda at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Dose Finding Study
What is being tested?: TAK-828
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 36 participants
Where: 2 sitesUnited States
Study dates: 1 Mar 2016to 17 Jun 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Is a healthy male and female (non-child bearing potential) participants.
Cohorts 1 and 2: non-Japanese participants aged 18 to 55 years, inclusive, with body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m^ 2), inclusive, and body weight greater than or equal (>=) 50 kilograms (kg).
Cohort 3: Japanese participants (born to Japanese parents and grandparents) aged 20 to 55 years, inclusive, with BMI of 18.5 to 25 kg/m^ 2, inclusive, and body weight >= 45 kg.

Who cannot join

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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Study site
Austin, Texas
Study site
Baltimore, Maryland

Other trials in United States

About this study

Official title: A Randomized, Double-Blind (Sponsor-Open), Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Escalating Single Doses of TAK-828 in Healthy Non-Japanese and Japanese Subjects

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.

Read the detailed description

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.

Conditions: Dose Finding Study
Being tested: TAK-828, Placebo
Keywords: Drug therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TAK-828Drug
TAK-828 oral solution
PlaceboDrug
TAK-828 placebo-matching oral solution

Study groups in NCT02706834
Study group	Role	What they receive
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo
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. Receives: Drug: TAK-828; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 up to 7 days after last dose of study drug (up to 52 days)

Secondary outcomes (4)

Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)
Measured: 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)
Measured: Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose
t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)
Measured: 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)
Measured: Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 201617 Jun 2016

First posted11 Mar 2016 (estimated)
Study start1 Mar 2016
Primary completion17 Jun 2016
Study completion17 Jun 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Dose Finding StudyStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02706834
Sponsor's protocol ID: TAK-828-1001
Other IDs: U1111-1177-8044
Status last verified: Jan 2018
First submitted: 8 Mar 2016
Last updated: 19 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Dose Finding Study trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind (Sponsor-Open), Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Escalating Single Doses of TAK-828 in Healthy Non-Japanese and Japanese Subjects
ClinicalTrials.gov ID: NCT02706834
Acronym / sponsor ID: TAK-828-1001
Conditions: Dose Finding Study
Keywords: Drug therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 1 Mar 2016
Primary completion: 17 Jun 2016 (actual)
Study completion: 17 Jun 2016 (actual)
First posted: 11 Mar 2016 (estimated)
Results: Posted 19 Oct 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 11

Arm	Type	Receives
Cohort 1, Sequence I	Experimental	Drug: TAK-828, Drug: PlaceboNon-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	Drug: TAK-828, Drug: PlaceboNon-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	Drug: TAK-828, Drug: PlaceboNon-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.
Cohort 1, Sequence IV	Experimental	Drug: TAK-828, Drug: PlaceboNon-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	Drug: TAK-828, Drug: PlaceboNon-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	Drug: TAK-828, Drug: PlaceboNon-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	Drug: TAK-828, Drug: PlaceboNon-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	Drug: TAK-828, Drug: PlaceboNon-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	Drug: TAK-828, Drug: PlaceboJapanese 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	Drug: TAK-828, Drug: PlaceboJapanese 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	Drug: TAK-828, Drug: PlaceboJapanese 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.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Is a healthy male and female (non-child bearing potential) participants.
Cohorts 1 and 2: non-Japanese participants aged 18 to 55 years, inclusive, with body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m^ 2), inclusive, and body weight greater than or equal (>=) 50 kilograms (kg).
Cohort 3: Japanese participants (born to Japanese parents and grandparents) aged 20 to 55 years, inclusive, with BMI of 18.5 to 25 kg/m^ 2, inclusive, and body weight >= 45 kg.

Key exclusion criteria (1 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TAK-828TAK-828 oral solution	Drug	Cohort 1, Sequence I, Cohort 1, Sequence II, Cohort 1, Sequence III, Cohort 1, Sequence IV, Cohort 2, Sequence I, Cohort 2, Sequence II, Cohort 2, Sequence III, Cohort 2, Sequence IV, Cohort 3, Sequence I, Cohort 3, Sequence II, Cohort 3, Sequence III
PlaceboTAK-828 placebo-matching oral solution	Drug	Cohort 1, Sequence I, Cohort 1, Sequence II, Cohort 1, Sequence III, Cohort 1, Sequence IV, Cohort 2, Sequence I, Cohort 2, Sequence II, Cohort 2, Sequence III, Cohort 2, Sequence IV, Cohort 3, Sequence I, Cohort 3, Sequence II, Cohort 3, Sequence III

Primary outcome

Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)
Time frame: Day 1 up to 30 days after last dose of study drug (up to 85 days)
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.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
Time frame: 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
Time frame: Day 1 up to 7 days after last dose of study drug (up to 52 days)
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.
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
Time frame: Day 1 up to 7 days after last dose of study drug (up to 52 days)
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.
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose
Time frame: Day 1 up to 7 days after last dose of study drug (up to 52 days)
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.

4 secondary outcomes

Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)
Time frame: 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)
Time frame: Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose
t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)
Time frame: 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)
Time frame: Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose

Results and safety

Results posted to the registry on 19 Oct 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1, Sequence I	3	1
Cohort 1, Sequence II	3	2
Cohort 1, Sequence III	3	2
Cohort 1, Sequence IV	3	3
Cohort 2, Sequence I	3	2
Cohort 2, Sequence II	3	3
Cohort 2, Sequence III	3	3
Cohort 2, Sequence IV	3	3
Cohort 3, Sequence I	4	4
Cohort 3, Sequence II	4	3
Cohort 3, Sequence III	4	3

Primary outcome: Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)

Time frame: Day 1 up to 30 days after last dose of study drug (up to 85 days). Number. Unit: percentage of participants

Measure	Cohort 1: Placebo n = 10	Cohort 1: TAK-828 0.1 mg/ Fasted n = 9	Cohort 1: TAK-828 0.5 mg/ Fasted n = 8	Cohort 1: TAK-828 15 mg/ Fasted n = 7	Cohort 1: TAK-828 100 mg/ Fasted n = 7	Cohort 1: TAK-828 100 mg/ Fed n = 8	Cohort 2: Placebo n = 9	Cohort 2: TAK-828 3 mg/ Fasted n = 9	Cohort 2: TAK-828 50 mg/ Fasted n = 9	Cohort 2: TAK-828 200 mg/ Fasted n = 9	Cohort 2: TAK-828 100 mg/ Fasted n = 9	Cohort 2: TAK-828 100 mg/ Fed n = 4	Cohort 3: Placebo n = 12	Cohort 3: TAK-828 15 mg/ Fasted n = 8	Cohort 3: TAK-828 100 mg/ Fasted n = 8	Cohort 3: TAK-828 150 mg/ Fasted n = 6
Value	30.0	55.6	37.5	14.3	0	12.5	0	11.1	11.1	11.1	22.2	0	0	25.0	75.0	66.7

Population analysed: Safety Set included all participants who received at least 1 dose of study drug.

Primary outcome: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

Time frame: Day 1 up to 30 days after last dose of study drug (up to 85 days). Number. Unit: percentage of participants

Measure	Cohort 1: Placebo n = 10	Cohort 1: TAK-828 0.1 mg/ Fasted n = 9	Cohort 1: TAK-828 0.5 mg/ Fasted n = 8	Cohort 1: TAK-828 15 mg/ Fasted n = 7	Cohort 1: TAK-828 100 mg/ Fasted n = 7	Cohort 1: TAK-828 100 mg/ Fed n = 8	Cohort 2: Placebo n = 9	Cohort 2: TAK-828 3 mg/ Fasted n = 9	Cohort 2: TAK-828 50 mg/ Fasted n = 9	Cohort 2: TAK-828 200 mg/ Fasted n = 9	Cohort 2: TAK-828 100 mg/ Fasted n = 9	Cohort 2: TAK-828 100 mg/ Fed n = 4	Cohort 3: Placebo n = 12	Cohort 3: TAK-828 15 mg/ Fasted n = 8	Cohort 3: TAK-828 100 mg/ Fasted n = 8	Cohort 3: TAK-828 150 mg/ Fasted n = 6
Value	0	11.1	0	0	0	0	0	0	0	0	0	0	0	0	12.5	0

Population analysed: Safety Set included all participants who received at least 1 dose of study drug.

Primary outcome: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose

Time frame: Day 1 up to 7 days after last dose of study drug (up to 52 days). Number. Unit: percentage of participants

Measure	Cohort 1: Placebo n = 10	Cohort 1: TAK-828 0.1 mg/ Fasted n = 9	Cohort 1: TAK-828 0.5 mg/ Fasted n = 8	Cohort 1: TAK-828 15 mg/ Fasted n = 7	Cohort 1: TAK-828 100 mg/ Fasted n = 7	Cohort 1: TAK-828 100 mg/ Fed n = 8	Cohort 2: Placebo n = 9	Cohort 2: TAK-828 3 mg/ Fasted n = 9	Cohort 2: TAK-828 50 mg/ Fasted n = 9	Cohort 2: TAK-828 200 mg/ Fasted n = 9	Cohort 2: TAK-828 100 mg/ Fasted n = 9	Cohort 2: TAK-828 100 mg/ Fed n = 4	Cohort 3: Placebo n = 12	Cohort 3: TAK-828 15 mg/ Fasted n = 8	Cohort 3: TAK-828 100 mg/ Fasted n = 8	Cohort 3: TAK-828 150 mg/ Fasted n = 6
Value	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Population analysed: Safety Set included all participants who received at least 1 dose of study drug.

Primary outcome: Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose

Time frame: Day 1 up to 7 days after last dose of study drug (up to 52 days). Number. Unit: percentage of participants

Measure	Cohort 1: Placebo n = 10	Cohort 1: TAK-828 0.1 mg/ Fasted n = 9	Cohort 1: TAK-828 100 mg/ Fasted n = 7	Cohort 1: TAK-828 100 mg/ Fed n = 8	Cohort 2: Placebo n = 9	Cohort 2: TAK-828 3 mg/ Fasted n = 9	Cohort 2: TAK-828 50 mg/ Fasted n = 9	Cohort 2: TAK-828 100 mg/ Fasted n = 9	Cohort 3: Placebo n = 12	Cohort 3: TAK-828 100 mg/ Fasted n = 8	Cohort 3: TAK-828 150 mg/ Fasted n = 6
SBP <85 mmHg: standing, after 1 minute	0	0	0	12.5	0	0	0	11.1	8.3	0	0
SBP <85 mmHg: standing, after 3 minutes	20.0	11.1	0	0	11.1	0	11.1	0	0	0	0
DBP <50 mmHg: supine, after 5 minutes	0	0	14.3	0	0	11.1	11.1	0	8.3	12.5

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Day 1 up to 30 days after last dose of study drug (up to 85 days).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: Placebo	0 of 10 (0%)	3 of 10 (30%)	Not reported
Cohort 1: TAK-828 0.1 mg/ Fasted	1 of 9 (11.1%)	5 of 9 (55.6%)	Not reported
Cohort 1: TAK-828 0.5 mg/ Fasted	0 of 8 (0%)	3 of 8 (37.5%)	Not reported
Cohort 1: TAK-828 15 mg/ Fasted	0 of 7 (0%)	1 of 7 (14.3%)	Not reported
Cohort 1: TAK-828 100 mg/ Fasted	0 of 7 (0%)	0 of 7 (0%)	Not reported
Cohort 1: TAK-828 100 mg/ Fed	0 of 8 (0%)	1 of 8 (12.5%)	Not reported
Cohort 2: Placebo	0 of 9 (0%)	0 of 9 (0%)	Not reported
Cohort 2: TAK-828 3 mg/ Fasted	0 of 9 (0%)	1 of 9 (11.1%)	Not reported
Cohort 2: TAK-828 50 mg/ Fasted	0 of 9 (0%)	1 of 9 (11.1%)	Not reported
Cohort 2: TAK-828 200 mg/ Fasted	0 of 9 (0%)	1 of 9 (11.1%)	Not reported
Cohort 2: TAK-828 100 mg/ Fasted	0 of 9 (0%)	2 of 9 (22.2%)	Not reported
Cohort 2: TAK-828 100 mg/ Fed	0 of 4 (0%)	0 of 4 (0%)	Not reported
Cohort 3: Placebo	0 of 12 (0%)	0 of 12 (0%)	Not reported
Cohort 3: TAK-828 15 mg/ Fasted	0 of 8 (0%)	2 of 8 (25%)	Not reported
Cohort 3: TAK-828 100 mg/ Fasted	0 of 8 (0%)	6 of 8 (75%)	Not reported
Cohort 3: TAK-828 150 mg/ Fasted	0 of 6 (0%)	4 of 6 (66.7%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Takeda

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-828 in people with Dose Finding Study, run by Takeda at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE) (time frame: Day 1 up to 30 days after last dose of study drug (up to 85 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02706834.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2018.