A SAD/MAD Study to Evaluate the Safety, Tolerability, PK and PD of MT2004

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of MT2004 following oral single and multiple ascending dose administration.

Detailed Description
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A total of 48 subjects will be evaluated with 36 subjects randomized to receive active drug and 12 subjects randomized to receive placebo in a double-blind fashion (eight subjects per each dose cohort, six subjects randomized to active drug and two subjects randomized to placebo). A separate open panel of 8 subjects will receive a single dose of MT2004 under fed conditions following the last of the SAD dose escalation cohorts. The dose level will be selected by the sponsor based upon the safety and PK data generated in each dose escalation cohort of the SAD part of the trial. A total of 24 subjects will receive MT2004 (8 subjects in each dose cohort for a total of 3 cohorts, 6 subjects randomized to active drug and 2 subjects randomized to placebo per cohort). MT2004 dosing regimens (dose levels and duration of administration) will be determined based on the collective SAD PK and safety data from Part 1 and nonclinical data of MT2004 (pharmacology and toxicology). Tentative dosing regimen is once daily for a consecutive 14 days.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Sequential Parallel Group, SAD/MAD Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MT2004

Conditions
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Healthy

Intervention / Treatment
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* Drug: MT2004
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are capable of giving informed consent and complying with study procedures; Are between the ages of 18 and 55 years, inclusive; Female subjects have a negative urine pregnancy test result at screening and Day -1, and meet one of the following criteria: Using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)] Surgically sterile for at least 3 months prior to screening by one of the following means: Bilateral tubal ligation Bilateral salpingectomy (with or without oophorectomy) Surgical hysterectomy Bilateral oophorectomy (with or without hysterectomy) Postmenopausal, defined as the following: Last menstrual period greater than 12 months prior to screening Postmenopausal status confirmed by serum follicle stimulating hormone (FSH) and estradiol levels at screening; Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, clinical laboratory tests, 12- lead ECG, and vital signs; Normal renal function as determined by Investigator following review of clinical laboratory test results; Non-smoker and no more than 2 tobacco-containing products including nicotine replacement products in last 6 months; Body mass index (BMI) of 18.0 to 30.0 kg/m2 inclusive and body weight not less than 50 kg; Willing and able to adhere to study restrictions and to be confined at the clinical research center. Male subjects with female partners of child bearing potential must agree to use condoms for the duration of the study and until 12 weeks after dosing with the study drug and must refrain from donating sperm for this same period. Exclusion Criteria: Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator; Known or suspected malignancy; History of pancreatitis or gall stones; History of unexplained syncope, symptomatic hypotension or hypoglycemia; Family history of long QTc syndrome; History of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance; History of organ transplantation with the exception of cornea transplantation; Poor venous access; Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody; Donated or lost >500ml of blood in the previous 3 months; Taken an investigational drug or participated in a clinical trial within 3 months (or 5 half- lives), whichever is longer; Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug; Hospital admission or major surgery within 6 months prior to screening; A history of prescription drug abuse, or illicit drug use within 9 months prior to screening; A history of alcohol abuse according to medical history within 9 months prior to screening; A positive screen for alcohol and/or drugs of abuse at screening or Day -1; An unwillingness or inability to comply with food and beverage restrictions during study participation; Use of over-the-counter (OTC) medication within 7 days, and herbal (including St John's Wort, herbal teas, garlic extracts) within 7 days prior to dosing (Note: Use of acetaminophen at < 2 g/day is permitted until 24 hours prior to dosing); Pregnant or breast feeding at screening or planning to become pregnant during the study; Inability to swallow multiple capsules simultaneously Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, sequential parallel group
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MT2004<br>MT2004 oral capsules treated group | Drug: MT2004<br>* MT2004 oral capsules<br>|
| Placebo Comparator: Placebo<br>Placebo oral capsules treated group | Drug: Placebo<br>* Placebo oral capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of MT2004 | Maximum observed concentration (Cmax) of MT2004 | 48 hours | 
| AUClast of MT2004 | Area under the concentration-time curve (AUC) from Hour 0 to the last measurable concentration (AUC0-last) of MT2004 | 48 hours | 
| Tmax of MT2004 | Time to maximum concentration (Tmax) | 48 hours | 
| T half of MT2004 | T half of MT2004 | 48 hours | 
| Plasma FGF19 Level | Plasma FGF19 Level | 24 hours | 
| Serum 7-alpha-hydroxy-4-cholesten-3-one (C4) Level | Serum 7-alpha-hydroxy-4-cholesten-3-one (C4) Level | 24 hours |