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

NCT02706834 | Completed Phase 1 Results

• 2 other identifiers: TAK-828-1001U1111-1177-8044
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Dose Finding Study

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (5)

• 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.

  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)

Secondary Outcomes (4)

• 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

• 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

Study Arms (11)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Drug: TAK-828; Drug: Placebo

Interventions

TAK-828 DRUG

TAK-828 oral solution

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

Placebo DRUG

TAK-828 placebo-matching oral solution

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Austin, Texas, United States

Location

Limitations and Caveats

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.

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 11, 2016
• Study Start: March 1, 2016
• Primary Completion: June 17, 2016
• Study Completion: June 17, 2016
• Last Updated: October 19, 2018
• Results First Posted: October 19, 2018

Record last verified: 2018-01

Locations

US (2)