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.
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). The total sample size will be up to 80 subjects to accommodate withdrawal of consent or replacement for other non-treatment-emergent adverse events (non-TEAE) reasons. SAD Levels 1-4 dosing: * Each of the SAD dose level cohorts will have 2 sentinel subjects followed at least 72 hours later by the remaining 6 subjects in 1 or more groups in a staggered fashion. Both sentinel subjects will be evaluated for 72 hours by the Investigator for safety prior to dosing the cohort's remaining 6 subjects. * Dosing will begin at dose Level 1 (10 mg). * Subjects in SAD Levels 1,3 and 4 will be dosed in a fed state (standard non-high-fat breakfast). * Subjects in the SAD Level 2, Two-Dose (20 mg) will be dosed in a fasting state on Day 1 with a subsequent 4-day washout period, followed by dosing in a fed state (standard not- high fat breakfast) on Day 6. * SAD Level 4 (80 mg) dosing is optional and may be adjusted based upon PK and safety results from earlier cohorts. MAD Levels 1-2 dosing: * The MAD portion of the study will commence at MAD Level 1 (10 mg) after the safe completion of the subjects in at least the SAD Level 2 Two-Dose cohort. * Subjects in MAD Levels 1-2 (no more than 20mg) will be dosed in a fed state (standard non-high-fat breakfast) over 14 continuous days of dosing. * MAD cohorts may be enrolled in small groups to accommodate clinic scheduling, with subjects dosed in a staggered fashion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
89
Safety and tolerability of oral MTR-601, a highly selective fast twitch myosin 2 ATPase inhibitor in normal healthy volunteers
Worldwide Clinical Trials
San Antonio, Texas, United States
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.
Time frame: From baseline to last follow-up visit (Day 7 for SAD Dose Levels 1, 3, and 4, Day 12 for SAD Dose Level 2, Day 20 MAD Dose Levels 1-6)
Maximum Plasma Concentration (Cmax) of MTR-601 In Single Ascending Doses
To evaluate the plasma and urine pharmacokinetics (PK) of MTR-601
Time frame: Day 1
Maximum Plasma Concentration (Cmax) of MTR-601 in Multiple Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Multiple Ascending Doses on Day 1
Time frame: Day 1
Maximum Plasma Concentration (Cmax) of MTR-601 in Multiple Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Multiple Ascending Doses on Day 7
Time frame: Day 7
Maximum Plasma Concentration at Steady State (Cmax, ss) of MTR-601 in Multiple Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Time to Maximum Plasma Concentration (Tmax) of MTR-601 in Single Ascending Doses
To evaluate the plasma and urine pharmacokinetics (PK) of MTR-601
Time frame: Day 1
Time to Maximum Plasma Concentration (Tmax) of MTR-601 in Multiple Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Multiple Ascending Doses on Day 1
Time frame: Day 1
Time to Maximum Plasma Concentration (Tmax) of MTR-601 in Multiple Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Multiple Ascending Doses on Day 7
Time frame: Day 7
Time to Maximum Plasma Concentration at Steady State (Tmax, ss) of MTR-601 in Multiple Ascending Doses
To Evaluate the Time to Maximum Plasma Concentration at Steady State (Tmax, ss) of MTR-601 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Plasma Area Under the Curve Through 24 Hours (AUC0-24) of MTR-601 in Single Ascending Doses
To evaluate the Plasma area under the curve (AUC0-24) of MTR-601 in Single Ascending Doses to 24 Hours
Time frame: 0-24 Hours
Plasma Area Under the Curve to Infinity (AUCinf) of MTR-601 in Single Ascending Dose
To extraplolate the plasma Area Under the Curve to infinite time of MTR-601 in Single Ascending Doses
Time frame: 0-96 hours
Plasma Half-life (T1/2) of MTR-601 in Single Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Single Ascending Doses
Time frame: 0-96 Hours
Plasma Concentration Corresponding to the Time of Last Measurable Observation (Clast)
To evaluate the plasma concentration corresponding to the time of last measurable observation of MTR-601 in Single Ascending Doses
Time frame: 0-96 Hours
Plasma Clearance of Drug After Extravascular Administration (CL/F) in Single Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Single Ascending Doses
Time frame: 0-96 Hours
Volume of Distribution After Extravascular Administration (Vz/F) of MTR-901 in Single Ascending Doses
To evaluate the volume of distribution after extravascular administration (Vz/F) of MTR-901 in Single Ascending Doses
Time frame: 0-96 Hours
Maximum Plasma Concentration at 24 Hours (C24) of MTR-601 in Multiple Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Multiple Ascending Doses on Day 1
Time frame: Day 1
Maximum Plasma Concentration at 24 Hours (C24) of MTR-601 in Multiple Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Multiple Ascending Doses on Day 7
Time frame: Day 7
Maximum Plasma Concentration at 24 Hours (C24) of MTR-601 in Multiple Ascending Doses
To evaluate the plasma pharmacokinetics (PK) of MTR-601 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Area Under the Curve Over the Dosing Interval (AUCtau) of MTR-601 in Multiple Ascending Doses
To evaluate the Area Under the Curve over the Dosing Interval (AUCtau) of MTR-601 in Multiple Ascending Doses on Day 1
Time frame: Day 1
Area Under the Curve Over the Dosing Interval (AUCtau) of MTR-601 in Multiple Ascending Doses
To evaluate the Area Under the Curve over the Dosing Interval (AUCtau) of MTR-601 in Multiple Ascending Doses on Day 7
Time frame: Day 7
Area Under the Curve at Steady State Over the Dosing Interval (AUCtau) of MTR-601 in Multiple Ascending Doses
To evaluate the Area Under the Curve at Steady State over the Dosing Interval (AUCtau) of MTR-601 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Average Plasma Drug Concentration of MTR-601 in Multiple Ascending Doses
To evaluate the Average plasma drug concentration of MTR-601 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Volume of Distribution After Extravascular Administration (Vz/F) of MTR-901 in Multiple Ascending Doses
To evaluate the Volume of Distribution After Extravascular Administration (Vz/F) of MTR-901 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Accumulation Ratio of Maximum Plasma Concentration (AR_Cmax) of MTR-901 in Multiple Ascending Doses
To evaluate the Accumulation Ratio of Maximum Plasma Concentration (AR\_Cmax) of MTR-901 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Maximum Accumulation Concentration of Area Under the Curve (AR_AUC0-24, qd) of MTR-901 in Multiple Ascending Doses
To evaluate the Maximum Accumulation Concentration of Area Under the Curve (AR\_AUC0-24, qd) of MTR-901 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Plasma Clearance of Drug After Extravascular Administration (CL/F) of MTR-601 in Multiple Ascending Doses
To evaluate the Plasma Clearance of Drug After Extravascular Administration (CL/F) of MTR-601 in Multiple Ascending Doses on Day 14
Time frame: Day 14
Cumulative Amount of MTR-601 Excreted Unchanged in Urine (Ae) in Single Ascending Doses
To evaluate the Cumulative amount of MTR-601 Excreted Unchanged in Urine in Single Ascending Doses
Time frame: Up to 96 Hours
Fraction of Dose of MTR-601 Excreted Unchanged in Urine (Fe) in Single Ascending Doses
To evaluate theFraction of Dose of MTR-601 Excreted Unchanged in Urine in Single Ascending Doses
Time frame: Up to 96 Hours
Renal Clearance (Clr) of MTR-601 in Single Ascending Doses
To evaluate the Renal Clearance (Clr) of MTR-601 in Single Ascending Doses in Single Ascending Doses
Time frame: Up to 96 Hours
Cumulative Amount of MTR-601 Excreted Unchanged in Urine (Ae) In Multiple Ascending Doses
To evaluate the Cumulative amount of MTR-601 Excreted Unchanged in Urine in Multiple Ascending Doses
Time frame: Day 1
Fraction of Dose of MTR-601 Excreted Unchanged in Urine (Fe) in Multiple Ascending Doses
To evaluate theFraction of Dose of MTR-601 Excreted Unchanged in Urine in Multiple Ascending Doses
Time frame: Day 1
Cumulative Amount of MTR-601 Excreted Unchanged in Urine (Ae) In Multiple Ascending Doses
To evaluate the Cumulative amount of MTR-601 Excreted Unchanged in Urine in Multiple Ascending Doses
Time frame: Day 7
Fraction of Dose of MTR-601 Excreted Unchanged in Urine (Fe) in Multiple Ascending Doses
To evaluate theFraction of Dose of MTR-601 Excreted Unchanged in Urine in Multiple Ascending Doses
Time frame: Day 7
Cumulative Amount of MTR-601 Excreted Unchanged in Urine (Ae) In Multiple Ascending Doses
To evaluate the Cumulative amount of MTR-601 Excreted Unchanged in Urine in Multiple Ascending Doses
Time frame: Day 14
Fraction of Dose of MTR-601 Excreted Unchanged in Urine (Fe) in Multiple Ascending Doses
To evaluate theFraction of Dose of MTR-601 Excreted Unchanged in Urine in Multiple Ascending Doses
Time frame: Day 14
Renal Clearance (Clr) of MTR-601 in Multiple Ascending Doses
To evaluate the Renal Clearance (Clr) of MTR-601 in Multiple Ascending Doses
Time frame: Day 14
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