A Study to Evaluate the Safety, Tolerability and Pharmacokinetics Profile of MT101-5 in Healthy Volunteers

NCT05844787 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MT101-PD-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The primary study objective is to establish the safety and tolerability of MT101-5 after a single and multiple dose administrations in healthy volunteers. The safety and overall tolerability of MT101-5 will be evaluated based on:

• Incidence of Dose Limiting Toxicities (DLTs)
• Incidence of Treatment-Emergent Adverse Events (TEAEs).
• Incidence of withdrawals due to Adverse Events (AEs).
• Change/shifts in laboratory values. Change in vital signs.
• Change in Electrocardiogram (ECG) parameters.
• Changes in physical examination findings

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (37)

• Incidence of Dose Limiting Toxicities (DLTs)

  Any clinically significant adverse event (AE)/serious adverse event (SAE) or clinically significant laboratory abnormality which is classified as \> Grade 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0), where applicable, deemed by the investigator as at least "possibly, probably or definitely related" to the drug but unrelated to concurrent illness, or concomitant medications.

  Day 1 through 7 days after the last study drug administration

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that occurs or is reported by the patient to have occurred, or a worsening of a pre-existing condition. An adverse event may or may not be related to the study treatment.

  Day 1 through 7 days after the last study drug administration

• Incidence of withdrawals due to Adverse Events (AEs)

  Incidence of withdrawals due to Adverse Events (AEs) defined above

  Day 1 through 7 days after the last study drug administration

• Change in complete blood count test

  Change from baseline to day 7 after the first study drug administration

• Change in comprehensive metabolic panel test

  Change from baseline to day 7 after the first study drug administration

• Change in urinalysis test

  Change from baseline to day 7 after the first study drug administration

• Change in pregnancy test

  Change from baseline to day 7 after the first study drug administration

• Change of blood pressure (both systolic and diastolic blood pressures)

  Change from pre-dose to 96 hours after last study drug administration

• Change of blood pressure (both systolic and diastolic blood pressures)

  Change from pre-dose to day 7 after the last study drug administration

• Change of pulse

  Change from pre-dose to 96 hours after last study drug administration

• Change of pulse

  Change from pre-dose to day 7 after the last study drug administration

• Change of temperature

  Change from pre-dose to 96 hours after last study drug administration

• Change of temperature

  Change from pre-dose to day 7 after the last study drug administration

• Change of respiratory rate

  Change from pre-dose to 96 hours after last study drug administration

• Change of respiratory rate

  Change from pre-dose to day 7 after the last study drug administration

• ECG ventricular rate (beats per minute)

  At pre-dose

• ECG ventricular rate (beats per minute)

  96 hours after study drug administration

• ECG ventricular rate (beats per minute)

  On day 7 after the last study drug administration

• PR interval (msec)

  At pre-dose

• PR interval (msec)

  96 hours after study drug administration

• PR interval (msec)

  On day 7 after the last study drug administration

• QRS interval (msec)

  At pre-dose

• QRS interval (msec)

  96 hours after study drug administration

• QRS interval (msec)

  On day 7 after the last study drug administration

• QT interval (msec)

  At pre-dose

• QT interval (msec)

  96 hours after study drug administration

• QT interval (msec)

  On day 7 after the last study drug administration

• QTc interval (msec)

  At pre-dose

• QTc interval (msec)

  96 hours after study drug administration

• QTc interval (msec)

  On day 7 after the last study drug administration

• Maximum observed plasma drug concentration (Cmax)

  0-96 hours

• Apparent terminal elimination half-life (t1/2)

  0-96 hours

• Time to maximum observed plasma drug concentration (Tmax)

  0-96 hours

• Area under the plasma drug concentration-time curve (AUC)

  0-96 hours

• Percentage of AUC0-∞ extrapolated from Tlast to infinity (AUCext)

  0-96 hours

• Apparent plasma clearance (CL/F)

  0-96 hours

• Apparent Volume of distribution (Vz/F)

  0-96 hours

Study Arms (3)

SAD Phase

EXPERIMENTAL

SAD Phase: including Food Interaction - Blinding and Randomization: This is a randomized, double-blind, placebo-controlled, sentinel design, dose-escalating study with 40 healthy volunteers. Subjects will be assigned to 1 of up to 5 cohorts and will be randomized within each cohort to MT101-5 or placebo, as follows: * cohort 1: 100 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo) * cohort 2: 150 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo) * cohort 3: 300 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo) * cohort 4: 450 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo) * cohort 5: 600 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo)

Drug: MT101-5

Food Interaction Phase

EXPERIMENTAL

Food Interaction Phase: Following the completion of the SAD phase, if study stopping criteria (SSC) is not met, then subjects in cohort 5 will cross-over to the fed part of the study following a 7 day washout period. If SSC is achieved in the SAD phase, then the previous dose will be in the Food Interaction phase.

Drug: MT101-5

MAD Phase

EXPERIMENTAL

MAD Phase; Blinding and Randomization: This is a randomized, double-blind, placebo-controlled study in approximately 8 elderly healthy volunteers. If study stopping criteria (SSC) is not met in the SAD phase, then subjects will be assigned to the cohort 5 dose. If SSC is achieved in the SAD phase, then the previous dose will be used as the cohort in the MAD phase

Drug: MT101-5

Interventions

MT101-5 DRUG

Tablet

Food Interaction Phase; MAD Phase; SAD Phase

Eligibility Criteria

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

You may qualify if:

• Subjects will be eligible for enrollment in the study only if they meet ALL of the following criteria:
• Age:
• SAD \& Food Interaction: Healthy male and female subjects, 18 to 45 years of age, inclusive.
• MAD: Elderly healthy male and female subjects ≥ 65 years of age
• BMI:
• SAD \& Food Interaction: The subject has a body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, and weighs at least 50 kg.
• MAD: The subject has a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and weighs at least 50 kg.
• The subject is in good health and has no medical condition of clinical significance or that may impact the outcome of the study, as determined by the investigator (as determined by medical history, physical examination, 12-lead electrocardiogram \[ECG\], vital signs, and clinical laboratory results at screening).
• The subject is able to understand the nature of the study and any potential hazards associated with participating in it.
• The subject is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study.
• The subject is willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided and has had the opportunity to discuss the study with the investigator or designee.
• Negative pregnancy test for female subjects of childbearing potential. Women of childbearing potential (WOCBP) and Women of non-childbearing potential are eligible to participate. Both women of childbearing potential and women of non-childbearing potential should use an approved method of birth control and agrees to continue to use this method for the duration of the study (and for 90 days after taking the last dose of MT101-5).
• Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (e.g., diaphragm, cervical cap, male condom, and female condom and spermicidal foam, sponges, and film) (WOCBP only), female subject/partner's use of an intrauterine device (IUD), or if the female subject/partner is surgically sterile at least three months before screening (confirmed by study doctor) or 2 years post-menopausal (patient reported) confirmed with FSH/estradiol levels at screening. All male subjects/partners must agree to consistently and correctly use a condom for the duration of the study and for 90 days after taking the study drug. In addition, subjects may not donate sperm for the duration of the study and for 90 days after taking study drug.

You may not qualify if:

• Subjects will be eligible for enrollment in the study only if they meet NONE of the following criteria:
• The subject has a history of severe allergic or anaphylactic reactions.
• The subject has a known allergy or hypersensitivity to any component of the formulation.
• The subject has a medical history or current evidence of any clinically significant (as determined by the investigator) cardiac, endocrine (including diabetes), hematologic, hepatobiliary (abnormal alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma-glutamyl transpeptidase \[GGT\], or total bilirubin), immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal condition, or other major disease.
• The subject has a history of any malignant disease.
• The subject has a history of more than one herpes zoster episode or multimetameric herpes zoster.
• The subject has a history of an opportunistic infection (e.g. cytomegalovirus, pneumocystis carinii, aspergillosis, clostridium difficile).
• The subject has a history of or ongoing chronic or recurrent infectious disease (e.g. infected indwelling prosthesis, osteomyelitis, chronic sinusitis).
• The subject has had major trauma or surgery in the 2 months before screening or at any time between screening and check-in.
• The subject has had an acute infection within 2 weeks before screening or at any time between screening and check-in including, but not limited to, history, signs, or symptoms of a common cold (e.g., mild rhinorrhea), untreated oral/dental abnormalities (e.g. untreated dental caries as determined by examination of the mouth), or untreated disruption of the skin.
• The subject has clinically significant abnormal ECG findings at screening, check-in visits, or predose, as determined by the Investigator.
• The subject has a supine blood pressure measurement outside the ranges of the below at screening, check-in, or predose. Note: If either value is out of the range, blood pressure measurements may be repeated in the supine position at intervals of 5 to 10 minutes up to 3 times. If the mean systolic or diastolic measurement continues to exceed the stated limits, the subject will be excluded.
• SAD: Ranges 90 to 140 mm Hg systolic or 45 to 90 mm Hg diastolic (measured after a rest of at least 5 minutes)
• MAD: Ranges 90 to 150 mm Hg systolic or 45 to 95 mm Hg diastolic (measured after a rest of at least 5 minutes)
• The subject has a pulse of fewer than 45 beats per minute (bpm) or greater than 100 bpm (measured after a rest of at least 5 minutes) at screening, check-in, or predose.

Sponsors & Collaborators

• Mthera Pharma Co., Ltd.: lead
• Amarex Clinical Research: collaborator

Study Sites (1)

Frontage Clinical Services, 1nc.

Secaucus, New Jersey, 07094, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Ascending Dose (SAD) Study Including a Food Interaction Study, Followed by a Multiple Ascending Dose (MAD) Study.

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: May 6, 2023
• Study Start: July 11, 2022
• Primary Completion: February 23, 2023
• Study Completion: February 23, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-04

Locations

US (1)