Clinical trial NCT03809039: A Study to Investigate the Safety, Tolerability and Pharmacokinetics of MT-6345 in Healthy Subjects
Official title: A Randomised, Double-Blind, Placebo-Controlled Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of MT-6345 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Mitsubishi Tanabe Pharma America Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-18
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: The purpose of this study is to Investigate the Safety, Tolerability and Pharmacokinetics of MT-6345 in Healthy Subjects.


Eligibility criteria: Inclusion Criteria:

Additional screening criteria check may apply for qualification:

* Able to provide written informed consent to participate in this study after reading the participant information sheet and Informed Consent Form (ICF), and after having the opportunity to discuss the study with the Investigator or designee.
* Healthy and free from clinically significant illness or disease as determined by medical history, physical examination, laboratory and other tests at Screening and Day -1.
* A body weight of ≥60 kg for males and ≥50 kg for females and a body mass index (BMI) (Quetelet index) ranging from 18 to 30.0 kg/m2 inclusive at Screening and Day -1.
* In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the Protocol restrictions and requirements.

Exclusion Criteria:

Additional screening criteria check may apply for qualification:

* Subjects with clinically significant (in the opinion of the Investigator) endocrine, thyroid, hepatic, respiratory, gastrointestinal, neurological, renal, cardiovascular disease, or history (within the last 5 years) of any significant psychiatric/psychotic illness disorder (including anxiety, depression and reactive depression).
* Female subjects who are pregnant (positive pregnancy test at Screening or Day -1) or lactating.
* Having previously received MT-6345 as part of this study.
* Clinically relevant abnormal medical history, physical findings or laboratory values at Screening or Day -1 that could interfere with the objectives of the study or the safety of the subject, as judged by the Investigator.
* Subjects who test positive for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus (HIV)-1 or HIV-2 antibodies at Screening.

Primary outcomes:
measure: Number of Participants With Mild, Moderate and Severe Adverse Events
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Time to Maximum Plasma Concentration (Tmax) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Plasma Terminal Elimination Half Life (t½) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hour. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Terminal Elimination Rate Constant (Kel) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Mean Residence Time (MRT) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Apparent Oral Clearance (CL/F) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUC0-t) of MT-6345.
timeFrame: up to 2 weeks after dosing
measure: Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345
timeFrame: Part 1 and Part 2: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72 (Day 4), 120 (Day 6), 192 (Day 9), and 336 (Day 15 Follow-up Visit) hours. Part 3: Pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours.
measure: Linearity Factor (LF) of MT-6345
timeFrame: up to 2 weeks after dosing
measure: Accumulation Ratio (RA) of MT-6345
timeFrame: up to 2 weeks after dosing
measure: Urinary Excreted Amount of Test Compound (Ae) of MT-6345
timeFrame: Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours)
measure: Urinary Excreted Amount of Test Compound Expressed as a Percentage of the Dose Administered (Ae%) of MT-6345
timeFrame: Day 1 (pre-dose and post-dose at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 16 hours) and Day 2 to Day 10 (pre-dose on each day)
measure: Renal Clearance (CLR) of MT-6345
timeFrame: Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours)
Other outcomes:
Locations:
city: City Name
country: United Kingdom
facility: Investigational center
Study officials:
affiliation: Mitsubishi Tanabe Pharma America Inc.
name: Head of Medical Science,
role: STUDY_DIRECTOR
References: