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

Dose Finding Study Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02706834
• Other study ID #: TAK-828-1001
• Secondary ID: U1111-1177-8044
• Status: Completed
• Phase: Phase 1
• Start date: March 1, 2016
• Est. completion date: June 17, 2016

Study information

• Verified date: January 2018
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 17, 2016
• Est. primary completion date: June 17, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria: -

1. Is a healthy male and female (non-child bearing potential) participants.

2. 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).

3. 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.

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.

Related Conditions & MeSH terms

• Dose Finding Study

Intervention

Drug:
• TAK-828
TAK-828 oral solution
• Placebo
TAK-828 placebo-matching oral solution

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 1 up to 30 days after last dose of study drug (up to 85 days)
Primary	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)
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.	Day 1 up to 7 days after last dose of study drug (up to 52 days)
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.	Day 1 up to 7 days after last dose of study drug (up to 52 days)
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.	Day 1 up to 7 days after last dose of study drug (up to 52 days)
Secondary	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
Secondary	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
Secondary	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
Secondary	AUC8: 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