Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals

NCT06117020 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MTR-601-NHV-101
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the safety and tolerability of single and multiple doses of MTR-601 in normal healthy volunteers under fed and fasted conditions. To evaluate the plasma and urine pharmacokinetics (PK) of MTR-601. To evaluate the pharmacodynamic (PD) effects of MTR-601 on muscle strength and muscle accumulation of MTR-601 by muscle biopsy and other potential mechanistic, predictive and PD markers of MTR-601.

Conditions

Muscle Spasticity; Hypertonia, Muscle; Cerebral Palsy; Multiple Sclerosis; Stroke; Hereditary Spastic Paraplegia; Dystonia; Spinal Cord Injuries

Keywords

Fast twitch type 2 myosin ATPase

Outcome Measures

Primary Outcomes (1)

• Incidence, severity and relatedness of Treatment-emergent adverse events (TEAEs). TEAE severity will be measured as mild, moderate or severe, and relatedness will be either related or not related.

  To assess the safety and tolerability of single and multiple doses of MTR-601 in normal healthy volunteers under fed and fasted conditions.

  From baseline to day 18.

Secondary Outcomes (9)

• Maximum plasma concentration (Cmax) of MTR-601

  From baseline to day 18.

• Time to maximum plasma concentration (Tmax) of MTR-601

  From baseline to day 18.

• Plasma area under the curve (AUC) concentration of MTR-601

  From baseline to day 18.

• Plasma half-life (T1/2) of MTR-601

  From baseline to day 18.

• Urine concentration of MTR-601

  From baseline to day 18.

Other Outcomes (1)

• Exploratory biomarkers of MTR-601 activity.

  From baseline to day 18.

Study Arms (2)

MTR-601

EXPERIMENTAL

Safety and tolerability of oral MTR-601, a highly selective fast twitch myosin 2 ATPase inhibitor in normal healthy volunteers

Drug: MTR-601

Placebo

PLACEBO COMPARATOR

Drug: MTR-601

Interventions

MTR-601 DRUG

Safety and tolerability of oral MTR-601, a highly selective fast twitch myosin 2 ATPase inhibitor in normal healthy volunteers

Also known as: Placebo

MTR-601; Placebo

Eligibility Criteria

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

You may qualify if:

• Willing to adhere to study procedures and provide written informed consent prior to the start of any study procedures.
• years of age at the time of consent and in good physical health based on medical history, physical examination including vital signs, as well as laboratory, electrocardiogram (ECG), Echocardiography (LVEF in the normal range of 50-70%), normal muscle strength upon physical examination, and spirometry test values in the normal range.
• Weight ≥50 kg and body mass index (BMI) \<33 kg/m2.
• Females or males with female partners must use a medically accepted contraceptive regimen (i.e., condoms with spermicide, abstinence, nonhormonal intrauterine device (IUD), Essure procedure, or diaphragm with spermicide) from at least 30 days prior to first dose through 90 days after the last dose OR females must be of non-childbearing potential, defined as:
• Have been surgically sterilized (bilateral oophorectomy) or hysterectomized at least 6 months prior to screening. Surgical sterilization procedures or hysterectomy must be supported with clinical documentation/medical records and noted in the Relevant Medical History/Current Medical Condition section of the electronic case report form (eCRF).
• Non-smoker and must not have used any tobacco products within 3 months prior to screening.
• In good physical and mental health as determined by past medical history, physical examination, psychiatric examination, 12-lead ECG, Echocardiography, spirometry, urinary system ultrasound, vital sign measurements, and clinical laboratory evaluations and calculations(e.g., eGFR greater than 90 ml/1.73 m2) at screening or check-in to the clinical research unit (CRU) on Day -1, as assessed by the Investigator (or designee). Congenital nonhemolytic hyperbilirubinemia; or suspicion of Gilbert's syndrome based on total and direct bilirubin is not acceptable.
• Has clinical laboratory test results within the reference ranges of the testing laboratory, except for results outside reference ranges that are deemed not clinically significant by the Investigator (or designee) at screening and check-in to the CRU on Day -1.
• Vital signs are within normal limits and FVC (after 3 minutes resting in supine position, will be measured in the seated position) is greater than 90% of the predicted value for gender, age and height with good expiratory effort.

You may not qualify if:

• History of, or physical examination findings indicating, clinically significant endocrine, neurological, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or muscle abnormalities or diseases that, in the opinion of the Investigator, would render the subject being unsuitable for the study.
• Unwilling or unable to refrain from strenuous exercise for 3 days prior to check-in and during study.
• Unwilling to discontinue coffee (containing caffeine) and other caffeine-containing beverages (e.g., sodas, energy drinks) for at least 72 hours before check-in and throughout the entirety of the study.
• Use of tobacco- or nicotine-containing products (including but not limited to cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 3 months prior to check-in to the CRU on Day -1 and throughout the entirety of the study (urine cotinine levels will be measured during screening for all subjects; subjects with cotinine values greater than 500 ng/mL will be excluded).
• Requires prescription or nonprescription medications/herbal remedies/supplements of any kind (with the exception of paracetamol/acetaminophen 2 g/day for up to 3 consecutive days) from 14 days prior to check-in (Day -1) and throughout the entirety of the study; uses or intends to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing.
• History or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, urinary, hematological, pulmonary, gastrointestinal, neurological, psychiatric, respiratory, or endocrine disorder, unless determined by the Investigator (or designee) and agreed by the Medical Monitor to be not clinically significant.
• Active or history of metabolic, cardiovascular, or cerebrovascular disease, including hypertension, angina, ischemic heart disease, transient ischemic attacks, bundle branch block, evidence of myocardial ischemia, stroke, and peripheral arterial disease sufficient to cause symptoms and/or require therapy to maintain stable status.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• Active neoplastic disease or history of any neoplastic disease within 5 years of screening (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitively treated with standard of care).
• Active infection (e.g., sepsis, pneumonia, abscess) or a serious infection (e.g., resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to dosing.
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
• Any of the following at screening and/or pre-dose:
• QT interval corrected for heart rate using Fridericia's formula (QTcF), QRS duration, PR interval outside of normal limits confirmed by repeat measurement, unless deemed non-clinically significant by PI and agreed by Medical Monitor
• Findings which would make QTc measurements difficult or QTc data uninterpretable
• History of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome)

Sponsors & Collaborators

• Motric Bio: lead

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

Related Publications (1)

• Gyimesi M, Horvath AI, Turos D, Suthar SK, Penzes M, Kurdi C, Canon L, Kikuti C, Ruppel KM, Trivedi DV, Spudich JA, Lorincz I, Rauscher AA, Kovacs M, Pal E, Komoly S, Houdusse A, Malnasi-Csizmadia A. Single Residue Variation in Skeletal Muscle Myosin Enables Direct and Selective Drug Targeting for Spasticity and Muscle Stiffness. Cell. 2020 Oct 15;183(2):335-346.e13. doi: 10.1016/j.cell.2020.08.050. Epub 2020 Oct 8.

  PMID: 33035452 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Muscle Spasticity; Muscle Hypertonia; Cerebral Palsy; Multiple Sclerosis; Stroke; Spastic Paraplegia, Hereditary; Dystonia; Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Dyskinesias; Spinal Cord Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Alan Hand, MD

  Worldwide Clinical Trials

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind - placebo-controlled.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This randomized, placebo-controlled, first-in-human (FIH) study of MTR-601 in normal healthy volunteers will consist of 3 single ascending dose (SAD) level cohorts, 1 SAD Level 2, Two-Dose cohort, 3 multiple ascending dose (MAD) level cohorts, and 1 optional MAD level cohort, each comprised of 8 subjects (6 MTR-601; 2 placebo).

Study Record Dates

• First Submitted: October 17, 2023
• First Posted: November 3, 2023
• Study Start: September 11, 2023
• Primary Completion: October 16, 2024
• Study Completion: October 16, 2024
• Last Updated: March 12, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)