Study to Evaluate the Effect of a Single Oral Dose of MT-7117 on the QT/QTc Interval in Healthy Subjects

NCT05241535 | Completed Phase 1 FDA Drug

• 1 other identifier: MT-7117-Z-103
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the effect of a single oral dose of MT-7117 on the QT/QTc interval in healthy subjects.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• Placebo-corrected, baseline-adjusted QTcF (corrected QT interval using the Fridericia formula) interval (ΔΔQTcF) at designed time points up to 24 hours post-dose

  The upper bound of the one-sided 95% confidence interval (CI) for the ΔΔQTcF at geometric mean Cmax (maximum plasma concentration) level is \<10 milliseconds.

  Pre-dose, 15 minutes post dose, 30 minutes post dose, 1 hour post dose, 2 hours post dose, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

Secondary Outcomes (14)

• Absolute values and changes in QTcF interval, PR (retrograde P waves), and QRS (Q wave, R wave, and S wave) values from Baseline at each timepoint.

  Pre-dose, 15 minutes post dose, 30 minutes post dose, 1 hour post dose, 2 hours post dose, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• Absolute values and changes in heart rate (HR) from Baseline at each timepoint.

  Pre-dose, 15 minutes post dose, 30 minutes post dose, 1 hour post dose, 2 hours post dose, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• The lower bound of the one-sided 95% CI of the ΔΔQTcF is >5 milliseconds at one or more individual timepoints between 1 hour and 4 hours after a single dose of moxifloxacin.

  1 hour post dose, 2 hours post dose, 3 hours post dose and 4 hours post dose

• The slope in concentration-response analysis for moxifloxacin is significantly positive from zero and the lower bound of the two-sided 90% CI of the predicted ΔΔQTcF at the geometric mean Cmax exceeds 5 milliseconds.

  Pre-dose, 15 minutes post dose, 30 minutes post dose, 1 hour post dose, 2 hours post dose, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• Proportion of subjects with a QTcF interval >=450, >=480, and >=500 milliseconds.

  Pre-dose, 15 minutes post dose, 30 minutes post dose, 1 hour post dose, 2 hours post dose, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

Study Arms (3)

Sequence 1 (starting with MT-7117 or Placebo)

EXPERIMENTAL

Treatment A or B (a single oral dose of MT-7117 or Placebo), Treatment C (a single oral dose of moxifloxacin)", then Treatment A or B (a single oral dose of placebo or MT-7117).

Drug: MT-7117; Drug: moxifloxacin; Drug: Placebo

Sequence 2 (starting with MT-7117 or Placebo)

EXPERIMENTAL

Treatment A or B (a single oral dose of placebo or MT-7117), Treatment A or B (a single oral dose of MT-7117 or Placebo), then Treatment C (a single oral dose of moxifloxacin).

Drug: MT-7117; Drug: moxifloxacin; Drug: Placebo

Sequence 3 (starting sequence with Moxifloxacin)

EXPERIMENTAL

Treatment C (A single oral dose of moxifloxacin), Treatment A or B (a single oral dose of placebo or MT-7117), then Treatment A or B (a single oral dose of MT-7117 or Placebo).

Drug: MT-7117; Drug: moxifloxacin; Drug: Placebo

Interventions

MT-7117 DRUG

oral

Sequence 1 (starting with MT-7117 or Placebo); Sequence 2 (starting with MT-7117 or Placebo); Sequence 3 (starting sequence with Moxifloxacin)

moxifloxacin DRUG

oral

Sequence 1 (starting with MT-7117 or Placebo); Sequence 2 (starting with MT-7117 or Placebo); Sequence 3 (starting sequence with Moxifloxacin)

Placebo DRUG

oral

Sequence 1 (starting with MT-7117 or Placebo); Sequence 2 (starting with MT-7117 or Placebo); Sequence 3 (starting sequence with Moxifloxacin)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to provide written informed consent to participate in this study after reading the participant information sheet and Informed Consent Form (ICF) and having the opportunity to discuss the study with the Investigator or designee.
• Healthy male or female subjects, 18-45 years of age, inclusive, at the time of signing the ICF.
• Subjects must weigh at least 50 kilograms (kg) (110 pounds) but no more than 95 kg (209 pounds) and have a body mass index (BMI) 18.0 to 30.0 kg/m2 both inclusive at Screening and on Day -1.
• Female subjects must not be lactating and must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours before receiving the first dose of IMP (Investigational Medicinal Product).
• Female subjects of childbearing potential and male subjects with a partner of childbearing potential must agree to use 2 effective methods of contraception (in female subjects, one method must be highly effective).
• Male subjects must agree not to donate sperm and female subjects must agree not to donate ova until 3 months after the last dose of IMP.
• In the Investigator's opinion, the subject can understand the nature of the study and any risks involved in participation and is willing to cooperate and comply with the protocol restrictions and requirements.

You may not qualify if:

• Presence or history of any hepatobiliary disease at Screening, determined clinically significant by the Investigator after discussion with Sponsor's Responsible Physician. Current, or history of, clinically significant (in the opinion of the Investigator and Sponsor Responsible Physician) endocrine, respiratory, neurological, gastrointestinal, renal, cardiovascular disease, or history (within the last 2 years) of any clinically significant psychiatric/psychotic illness disorder (including anxiety, depression, and reactive depression).
• 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.
• Subject with a history of gastrointestinal surgery or disease known to affect absorption, metabolism, or excretion of the IMP (other than surgical history of appendectomy and hernia repair / herniorrhaphy / hernioplasty are permitted).
• Subjects who have had major surgery within 3 months of Day 1.
• Family history of long or short QT syndrome, hypokalemia, syncope, or Torsades de Pointes.
• Clinically significant 12-lead ECG abnormalities, including subjects with QTcF of ≥450 msec at Screening or Day -1. A repeat assessment is allowed at each visit. If the repeat measurement is in range, the subject may be included.
• Subjects with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin ≥1.5 × upper limit of normal reference range at Screening or Day -1. A repeat assessment is allowed at each visit. If the repeat measurement is in range, the subject may be included.
• Blood pressure (supine) at Screening or Day -1 outside the range 90-145 mmHg (systolic) or 50-95 mmHg (diastolic); and resting heart rate (HR) outside the range of 45-100 bpm. A repeat assessment is allowed at each visit. If the repeat measurement is in range, the subject may be included.
• Receipt of any prescribed or nonprescribed systemic or topical medication within 30 days (or, if relevant, 5 half-lives, whichever is longer) prior to the first dose of study drugs unless, in the opinion of the Investigator and Sponsor, the medication will not interfere with the study procedures or compromise subject safety.
• Occasional use of paracetamol (acetaminophen) for mild analgesia is permitted.
• Vitamins and herbal supplements are not permitted 14 days prior to dosing.
• Presence or history of severe adverse reaction or allergy to any drug or excipient or other allergies that are of clinical significance to the study drugs.
• Previously having received MT-7117.
• History or presence of melanoma and/or lesions suspicious for melanoma at Screening.
• a. Subjects with the presence of a skin lesion suspicious for dysplastic nevus or a history of histologically proven dysplastic nevus.

Sponsors & Collaborators

• Tanabe Pharma America, Inc.: lead

Study Sites (2)

Daytona Beach Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

Dallas Clinical Research Unit

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Head of Medical Science

  Tanabe Pharma America, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Partially blinded. Placebo tablets to match active MT-7117 tablets
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 1, randomized, partial double-blind, placebo and positive-controlled, three-way crossover study to evaluate the effect of a single oral dose of MT-7117, placebo, and positive control, moxifloxacin, on the QT/QTc interval in healthy subjects. The study consists of 3 treatments administered in a specific sequence as per the randomization list. Each subject will receive all 3 treatments over a specific sequence.

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: February 15, 2022
• Study Start: January 12, 2022
• Primary Completion: February 23, 2022
• Study Completion: February 27, 2022
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)