Study to Determine the Effect of the Timing of a Meal on the Pharmacokinetics of Entinostat

Healthy Volunteers Clinical Trial

Official title:

A 2-Stage, Open-Label, Randomized, Single-Dose, Crossover Study to Determine the Effect of the Timing of a Meal on the Pharmacokinetics of Entinostat in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02922946
• Other study ID #: SNDX-275-0180
• Status: Completed
• Phase: Phase 1
• Start date: October 11, 2016
• Est. completion date: June 26, 2017

Study information

• Verified date: August 2018
• Source: Syndax Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are to evaluate the effect of the timing of a moderate-fat meal on the single dose pharmacokinetics of entinostat and to evaluate the safety and tolerability of entinostat under fed and fasting conditions in healthy adult subjects.

Description:

This is a 2-stage food effect (timing of the meal) study. A total of 48 subjects will be dosed if Stage 2 is conducted.

Stage 1 will be conducted as an open-label, randomized, 2-way crossover study. On Day 1 of each period, subjects will receive a single, oral dose of entinostat under fasting or fed conditions.

If preliminary results in Stage 1 indicate that the timing of a meal exhibits significant effect on the bioavailability of entinostat, then Stage 2 will be conducted which will investigate the effect of a meal either before or after dosing of entinostat on entinostat PK.

Stage 2 will be conducted as an open-label, randomized, 3-way crossover study. On Day 1 of each period, subjects will receive a single, oral dose of entinostat under fasting or fed conditions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: June 26, 2017
• Est. primary completion date: May 20, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy adults 19-55 years of age at screening.

• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to first dose and throughout the study.

• Body mass index of = 18.5 at screening.

• Medically healthy with no significant medical history, physical examination, laboratory values, vital signs, or ECGs. Liver function tests and serum bilirubin must be = the upper limit of normal. Platelets, hemoglobin, and hematocrit must be > the lower limit of normal at screening.

• Females of non-childbearing potential must have undergone sterilization procedures as noted in protocol at least 6 months prior to dose.

• Non-vasectomized male subjects must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond dose of study drug.

• Male subjects must agree not to donate sperm from the first dose until 90 days beyond dose of study drug.

• Understands the study procedures in the informed consent form and be willing and able to comply with the protocol.

Exclusion Criteria:

• Mentally or legally incapacitated or has significant emotional problems at screening or expected during the conduct of the study.

• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.

• History of illness that might confound the results of the study or poses an additional risk to the subject by their participation in the study in the opinion of the PI or designee.

• History of presence of alcoholism or drug abuse within the past 2 years prior to dose.

• History or presence of clinically significant cancer, cardiovascular disorders, acute or chronic gastrointestinal conditions in the opinion of the PI.

• Females of childbearing potential.

• Females with a positive pregnancy test or lactating.

• Positive urine drug or alcohol results are screening or each check-in.

• Positive urine cotinine at screening.

• Positive results are screening for HIV, hepatitis B surface antigen, or hepatitis C virus

• Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.

• Seated heart rate lower than 40 bpm or higher than 99 bpm at screening.

• QTcB interval (correction value of the interval between the Q and T waves on the ECG tracing using the Bazett Correction Formula) > 460 msec for males or > 480 msec for females or has ECG findings deemed abnormal by the PI or designee.

• Estimated creatinine clearance < 90 mL/min at screening.

• Unable to refrain from or anticipates the use of any prescription or non-prescription medications and any drugs known to be significant inhibitors or CYP (Cytochromes 450) enzymes and/or P-gp.

• Has been on a diet incompatible with the on-study diet within 28 days prior to dose and throughout the study in the opinion of the PI or designee.

• Is lactose intolerant.

• Donation of blood or significant blood loss within 56 days prior to dose.

• Plasma donation within 7 days prior to dose.

• Participation in another clinical study 28 days prior to dose.

Related Conditions & MeSH terms

• Healthy Volunteers
• Human Volunteers
• Normal Volunteers
• Volunteers

Intervention

Drug:
• Entinostat
HDAC (histone deacetylase) inhibitor

Locations

Country	Name	City	State
United States	Celerion	Lincoln	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Syndax Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC0-t (area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) for entinostat under fed and fasting conditions		Pre-dose through Day 22
Primary	AUC0-inf (area under the concentration-time curve, from time 0 extrapolated to infinity) for entinostat under fed and fasting conditions		Pre-dose through Day 22
Primary	Cmax (maximum observed concentration) of entinostat under fed and fasting conditions		Pre-dose through Day 22
Primary	AUC%extrap (percent of AUC0-inf extrapolated) of entinostat under fed and fasting conditions		Pre-dose through Day 22
Primary	Tmax (time to reach maximum observed concentration) of entinostat under fed and fasted conditions		Pre-dose through Day 22
Primary	Kel (apparent terminal elimination rate constant) of entinostat under fed and fasted conditions		Pre-dose through Day 22
Primary	T1/2 (apparent terminal elimination half-life) of entinostat under fed and fasted conditions		Pre-dose through Day 22
Primary	Changes from baseline in physical exam		Baseline through Day 1
Primary	Changes from baseline in vital signs		Baseline through Day 22
Primary	Changes from baseline in ECG results		Baseline through Day 22
Primary	Changes from baseline in adverse events		Baseline through 14 days after last sample collection
Primary	Changes from baseline in clinical laboratory tests		Baseline through Day 1