A Study to Investigate the Safety, Tolerability and Pharmacokinetics of MT-6345 in Healthy Subjects

Healthy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03809039
• Other study ID #: MT-6345-E01
• Secondary ID: 2018-002478-39
• Status: Terminated
• Phase: Phase 1
• Start date: January 15, 2019
• Est. completion date: July 1, 2020

Study information

• Verified date: May 2023
• Source: Mitsubishi Tanabe Pharma America Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 52
• Est. completion date: July 1, 2020
• Est. primary completion date: July 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• MT-6345
MT-6345
• MT-6345 Placebo
MT-6345 Placebo

Locations

Country	Name	City	State
United Kingdom	Investigational center	City Name

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma America Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Mild, Moderate and Severe Adverse Events	The criteria of Mild, Moderate and Severe are as follows: Mild: The event is transient and easily tolerated by the subject.; Moderate: The event causes discomfort and interferes with the subject's general condition.; Severe: The event causes considerable interference with the subject's general condition and may be incapacitating.	Up to 6 weeks
Secondary	Maximum Plasma Concentration (Cmax) of MT-6345	Cmax was measured for MT-6345 for the PK analysis set (PKPOP) subjects in Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Time to Maximum Plasma Concentration (Tmax) of MT-6345	Tmax was measured for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Plasma Terminal Elimination Half Life (t½) of MT-6345	t1/2 was measured for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC0-24h) of MT-6345	AUC(0-24h) was computed for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of MT-6345	AUC(0-last) was computed for MT-6345 for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-8) of MT-6345	AUC(0-8) was calculated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Terminal Elimination Rate Constant (Kel) of MT-6345	Kel was estimated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Mean Residence Time (MRT) of MT-6345	MRT was calculated for the PKPOP subjects in Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Apparent Oral Clearance (CL/F) of MT-6345	CL/F was measured for MT-6345 in the PKPOP subjects of Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUC0-t) of MT-6345.		up to 2 weeks after dosing
Secondary	Apparent Volume of Distribution at Steady State (Vss/F) of MT-6345	Vss/F was measured for MT-6345 in the PKPOP subjects of Part 1 and Part 2, and on Day 1 in Part 3.	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.
Secondary	Linearity Factor (LF) of MT-6345		up to 2 weeks after dosing
Secondary	Accumulation Ratio (RA) of MT-6345		up to 2 weeks after dosing
Secondary	Urinary Excreted Amount of Test Compound (Ae) of MT-6345	Ae was measured for MT-6345 for the PKPOP subjects in Part 3.	Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours)
Secondary	Urinary Excreted Amount of Test Compound Expressed as a Percentage of the Dose Administered (Ae%) of MT-6345	Ae% was measured for MT-6345 for the PKPOP subjects in Part 3.	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)
Secondary	Renal Clearance (CLR) of MT-6345	CLR was measured for MT-6345 for the PKPOP subjects in Part 3. For Day 10, CLR was not calculated because AUC(0-24h) on the last day of dosing was not calculated.	Day 1 (0 hours to 24 hours) and Day 10 (0 hours to 24 hours)