A Study to Examine the Effect of Omeprazole, Famotidine, and an Acidic Beverage on the Pharmacokinetics of Entinostat in Healthy Adult Subjects

NCT02922933 | Completed Phase 1

• 1 other identifier: SNDX-275-0150
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is therefore to evaluate the effect of concomitant drugs through an increase of intra-gastric pH levels on the bioavailability of entinostat. The primary objectives of this study are to evaluate the effect of multiple doses of omeprazole, famotidine, and the effect of an acidic beverage in combination with omeprazole on the single-dose PK profile of entinostat. The secondary objectives are to evaluate the safety and tolerability of a single dose of entinostat when administered with multiple doses of omeprazole, famotidine, and when administered with an acidic beverage in combination with omeprazole.

Conditions

Volunteers; Healthy Volunteers; Human Volunteers; Normal Volunteers

Keywords

entinostat; Histone Deacetylase Inhibitor; HDAC

Outcome Measures

Primary Outcomes (3)

• AUC0-t (area under the concentration-time curve) for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage

  Pre-dose through Day 22

• AUC0-inf (area under the concentration-time curve, from time 0 extrapolated to infinity for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage (Part 3)

  Pre-dose through Day 22

• Cmax (maximum observed concentration) for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage (Part 3)

  Pre-dose through Day 22

Secondary Outcomes (3)

• AUC%extrap (percent of AUC0-inf extrapolated) for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage (Part 3)

  Pre-dose through Day 22

• Tmax (time to reach maximum observed concentration) for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage (Part 3)

  Pre-dose through Day 22

• Kel (apparent terminal elimination rate constant) for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage (Part 3)

  Pre-dose through Day 22

Other Outcomes (7)

• T1/2 (apparent terminal elimination half-life) for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage (Part 3)

  Pre-dose through Day 22

• CL/F (apparent total plasma clearance after oral (extravascular) administration)for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage (Part 3)

  Pre-dose through Day 22

• Vz/F (apparent volume of distribution during the terminal elimination phase) for entinostat administered with or without omeprazole (Part 1), with or without famotidine (Part 2), or omeprazole with and without acidic beverage

  Pre-dose through Day 22

Study Arms (3)

Omeprazole

ACTIVE COMPARATOR

Treatment A: 5mg entinostat on Day 1 Treatment B: 20mg omeprazole for 5 days with 5mg entinostat on Day 1

Drug: entinostat; Dietary Supplement: Omeprazole

Famotidine

ACTIVE COMPARATOR

Treatment C: 5mg entinostat on Day 1 Treatment D: 20mg famotidine on Days -1 and 1 with 5mg entinostat on Day 1

Drug: entinostat; Dietary Supplement: Famotidine

Acidic Beverage

ACTIVE COMPARATOR

Treatment E: 20mg omeprazole for 5 days with 5mg entinostat on Day 1 taken with water Treatment F: 20mg omeprazole for 5 days with 5mg entinostat on Day 1 taken with an acidic beverage

Drug: entinostat; Dietary Supplement: Omeprazole

Interventions

entinostat DRUG

HDAC (histone deacetylase inhibitor)

Also known as: SNDX-275, MS-275

Acidic Beverage; Famotidine; Omeprazole

Omeprazole DIETARY_SUPPLEMENT

Proton pump inhibitor

Also known as: Prilosec, Zegerid

Acidic Beverage; Omeprazole

Famotidine DIETARY_SUPPLEMENT

Histamine-2 blocker

Also known as: Pepcid

Famotidine

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 the protocol at least 6 months prior to first dose.
• Non-vasectomized male subjects must agree to use a condom with spermicide or abstain from sexual intercourse during the study and until 90 days beyond dose of study drug.
• Male subjects must agree not to donate sperm from the first dose and until 90 days beyond dose of study drug.
• For Part 3 only, must be able to consume approximately 240 mL of a non-diet cola beverage within approximately 3 minutes.
• Understands the study procedures in the informed consent form and be willing and able to comply with the protocol.

You may not qualify if:

• 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 hypersensitivity or idiosyncratic reaction to entinostat, omeprazole, famotidine, or Coca-Cola(r) Classic.
• 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 H. pylori breath test at screening for Parts 1 and .
• 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.

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (2)

Celerion

Tempe, Arizona, 85283, United States

Location

Celerion

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Interventions

entinostat; Omeprazole; omeprazole, sodium bicarbonate drug combination; Famotidine

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Azoles

Study Officials

• Laura Sterling, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2016
• First Posted: October 4, 2016
• Study Start: October 25, 2016
• Primary Completion: April 19, 2017
• Study Completion: May 8, 2017
• Last Updated: August 16, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)