This first-in-human (FiH) study consists of 2 parts: single ascending dose (SAD) with evaluation of food effect (Part 1) and multiple ascending dose (MAD) (Part 2). The primary purpose of this study is to evaluate the safety and tolerability of single ascending oral doses in Part 1 (SAD Including Evaluation of Food Effect) and multiple ascending oral doses in Part 2 (MAD) of MA-0211 in healthy adult participants. This study will also evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending and multiple ascending oral doses of MA-0211 in healthy adult participants. In addition, this study will evaluate the effect of a single oral dose of MA-0211 on the QT interval using Fridericia's Correction (QTcF); determine the effect of food on the PK of a single oral dose of MA-0211 as well as evaluate the effect of multiple oral doses of MA-0211 on the QTcF.
After a screening period of up to 29 days prior to study drug administration, eligible participants will be residential for a single period of 6 days/5 nights in Part 1 and 19 days/18 nights in Part 2 . Participants will be admitted to the clinical unit on day 2.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
320
Parexel - Baltimore
Baltimore, Maryland, United States
Safety and tolerability assessed by nature, frequency, and severity of Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Time frame: Up to day 26
Number of participants with vital sign abnormalities and /or adverse events (AEs)
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to day 26
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Time frame: Up to day 26
Safety assessed by routine 12- lead electrocardiogram (ECG)
The overall conclusion of the routine ECG will be recorded as normal, abnormal not clinically significant, or abnormal clinically significant.
Time frame: Up to day 26
Safety assessed by continuous 12- lead electrocardiogram (ECG)
The overall conclusion of the continuous ECG will be recorded as normal or abnormal, with a comment added if abnormal.
Time frame: Up to day 15
Safety assessed by Real-time cardiac monitoring (telemetry) (Part 1)
Number of participants with potentially clinically significant telemetry abnormalities.
Time frame: Day 1
Part 1: Pharmacokinetics (PK) of MA-0211 in plasma: area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf)
AUCinf will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 1: PK of MA-0211 in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)
AUClast will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 1: PK of MA-0211 in plasma: percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf(%extrap))
AUCinf(%extrap) will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 1: PK of MA-0211 in plasma: maximum concentration (Cmax)
Cmax will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 2 (Only First Dose and Last Dose): PK of MA-0211 in plasma: maximum concentration (Cmax)
Cmax will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 1: PK of MA-0211 in plasma: time prior to the time corresponding to the first measurable (nonzero) concentration (tlag)
tlag will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 2 (Only First Dose): PK of MA-0211 in plasma: time prior to the time corresponding to the first measurable (nonzero) concentration (tlag)
tlag will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 1: PK of MA-0211 in plasma: time of maximum concentration (tmax)
tmax will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 2 (Only First Dose and Last Dose): PK of MA-0211 in plasma: time of maximum concentration (tmax)
tmax will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 1: PK of MA-0211 in plasma: apparent total systemic clearance after extravascular dosing (CL/F)
CL/F will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 2 (Only Last Dose): PK of MA-0211 in plasma: apparent total systemic clearance after extravascular dosing (CL/F)
CL/F will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 1: PK of MA-0211 in plasma: terminal elimination half-life (t ½)
t ½ will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 2 (Only Last Dose): PK of MA-0211 in plasma: terminal elimination half-life (t ½)
t ½ will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 1: PK of MA-0211 in plasma: apparent volume of distribution during the terminal elimination phase after extravascular dosing (Vz/F)
Vz/F will be derived from the PK plasma samples collected.
Time frame: Up to day 6
Part 2 (Only Last Dose): PK of MA-0211 in plasma: apparent volume of distribution during the terminal elimination phase after extravascular dosing (Vz/F)
Vz/F will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 2: PK of MA-0211 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)
Ctrough will be derived from the PK plasma samples collected.
Time frame: Up to day 15
Part 2 (Only First Dose): PK of MA-0211 in plasma: area under the concentration-time curve from the time of dosing to 24 hours postdose (AUC24)
AUC24 will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 2 (Only Last Dose): PK of MA-0211 in plasma Area under the curve over a dosing interval (AUCtau)
AUCtau will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 2 (Only Last Dose): PK of MA-0211 in plasma: peak-trough ratio (PTR)
PTR will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 2 (Only Last Dose): PK of MA-0211 in plasma: accumulation ratio calculated using the area under the concentration-time curve (Rac(AUC))
Rac(AUC) will be derived from the PK plasma samples collected.
Time frame: Up to day 19
Part 1: Pharmacodynamic (PD) of MA-0211: Twelve peroxisome proliferator-activated receptor (PPAR) delta target genes expression levels
To assess the PD of MA-0211 in Part 1.
Time frame: Up to day 2
Part 2: (Only First Dose and Last Dose) PD of MA-0211: Twelve peroxisome proliferator-activated receptor (PPAR) delta target genes expression levels
To assess the PD of MA-0211 in Part 2.
Time frame: Up to day 15
Part 2: (Only First Dose and Last Dose) PD of MA-0211: Serum myostatin
To assess the PD of MA-0211 in Part 2.
Time frame: Up to day 15
Part 2: (Only First Dose and Last Dose) PD of MA-0211: follistatin levels
To assess the PD of MA-0211 in Part 2.
Time frame: Up to day 15
Part 2: PD of MA-0211: Plasma acyl-carnitine levels
To assess the PD of MA-0211 in Part 2.
Time frame: Up to day 15
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