The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of MLN3126 when administered as a single dose of tablets at escalating dose levels in healthy participants.
The drug tested in this study is called MLN3126. The study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and the potential effect of food on the PK of MLN3126 and its M-I metabolite following single oral dose administrations. This study planned to enroll approximately 48 healthy participants, who were to be enrolled in 1 of the 6 dose cohorts or matching placebo in an ascending fashion. Participants were randomly assigned to MLN3126 or placebo within each cohort- which remained undisclosed to the participant and study doctor during the study (unless there was an urgent medical need): * Cohort 1 - MLN3126 300 mg or matching placebo * Cohort 2 - MLN3126 600 mg or matching placebo * Cohort 3 - MLN3126 1000 mg or matching placebo * Cohort 3 - MLN3126 1000 mg or matching placebo (fed regimen) * Cohort 4 - MLN3126 1500 mg or matching placebo * Cohort 5 - MLN3126 2000 mg or matching placebo * Cohort 6 - Did not taken place due to termination of the study All participants were asked to take the required tablets at the same time throughout the study. This single-centre trial was conducted in The United States. Participants were confined to the clinic for 5 days, and were contacted by telephone on day 14 (±2days) for a follow-up assessment. This study was terminated after completion of Cohort 5 due to findings of study site non-compliance to Good Clinical Practice (GCP) regarding study documentation. There were no safety concerns.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
39
MLN3126 tablets
MLN3126 placebo-matching tablets
Unnamed facility
Eatontown, New Jersey, United States
Number of Participants That Experience At Least One Treatment-Emergent Adverse Event (TEAE) Post-Dose
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Up to Day 22
Percentage of Participants With Markedly Abnormal Clinical Laboratory Results Post-Dose
Clinical safety laboratory tests included clinical chemistry, hematology and urinalysis. The percentage of participants with any markedly abnormal laboratory finding during the study.
Time frame: Up to Day 16
Percentage of Participants With Markedly Abnormal Vital Signs Post-Dose
Vital signs included oral body temperature measurement, blood pressure, respiration rate, and pulse rate \[beats per minute (bpm) or heart rate\]. The percentage of participant with markedly abnormal vital signs findings during the study. OBP=Orthostatic Blood Pressure. All OBP measurements were standing.
Time frame: Up to Day 16
Percentage of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings Post-Dose
A standard 12-lead ECG was performed. The percentage of participants with markedly abnormal electrocardiogram (ECG) findings during the study.
Time frame: Up to Day 16
Cmax: Maximum Plasma Concentration of MLN3126 and Metabolite M-I
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
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Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)
Tmax: Time to Maximum Plasma Concentration of MLN3126 and Metabolite M-I
Tmax is the time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)
AUC(0-tlqc): Area Under the Plasma Concentration Time Curve of MLN3126 and Metabolite M-I From Time 0 to the Last Quantifiable Concentration
AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).
Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)
AUC(0-inf): Area Under the Plasma Concentration Time Curve of MLN3126 and Metabolite M-I From Time 0 to Infinity
AUC(0-inf) is measure of area under the curve from time 0 to infinity.
Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)
CL/F: Oral Clearance of MLN3126
CL/F is apparent clearance of the drug from the plasma, after extravascular administration.
Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)
T ½: Half-life of MLN3126 and Metabolite M-I
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)
Ae (0-96): Total Amount of MLN3126 and Metabolite M-I Excreted in the Urine
Ae (0-96) is the total amount of drug excreted in urine from time 0 to time 96 hours.
Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)
Fe: Fraction of MLN3126 Excreted in the Urine
Fe is the Fraction of drug excreted in urine, calculated as Fe=(Ae\[0-t\]/dose)×100.
Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)
Renal Clearance (CLr) of MLN3126 and Metabolite M-I
Renal clearance was calculated as CLr=Ae(0-96)/AUC (0-96).
Time frame: Pre-dose and multiple timepoints post-dose (Up to 96 Hours)