Drug InteractionPhase 1NCT03187015
A Study to Examine the Effects of Entinostat on Midazolam in Healthy Adult Subjects
A Phase 1 study testing Entinostat and Midazolam in people with Drug Interaction and Healthy Volunteer, run by Syndax Pharmaceuticals at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the effect of Entinostat on the bioavailability of Midazolam. The primary objective is to evaluate the effect of a single oral dose of entinostat on the pharmacokinetics (PK) of a single oral dose of midazolam in healthy subjects. Read more about this study
- Who is it for?
- Ages 19 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction, Healthy Volunteer
- What is being tested?
- Entinostat and Midazolam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 23 May 2017to 22 Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 1. Healthy, adult, male or female (of non childbearing potential only), 19-55 years of age, inclusive, at screening.
- Continuous non smoker who has not used nicotine containing products for at least 3 months prior to the first dose and throughout the study.
- Body mass index (BMI) ≥ 18.5 and ≤ 32 kg/m2 at screening.
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. Liver function tests (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP]) and serum bilirubin (total and direct) must be ≤ the upper limit of normal at screening for inclusion. Platelets, hemoglobin and hematocrit must be ≥ than the lower limit of normal at screening for inclusion.
- For a female of non childbearing potential: must have undergone one of the following sterilization procedures, and have official documentation, at least 6 months prior to the first dose:
- hysteroscopic sterilization;
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- bilateral tubal ligation or bilateral salpingectomy;
- hysterectomy;
- bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first dose and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status as per PI or designee judgment.
- A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to first dose of study drug. A male who has been vasectomized less than 4 months prior to study first dose must follow the same restrictions as a non vasectomized male).
- If male, must agree not to donate sperm from the first dose until 90 days after the last dose of study drug.
- Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.
Who cannot join
- Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit 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 any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose.
- History or presence of hypersensitivity or idiosyncratic reaction to entinostat or drugs with a benzamide structure (e.g., tiapride, remoxipride, clebropride), midazolam, related compounds, or inactive ingredients.
- History or presence of any of the following as deemed clinically significant in the opinion of the PI or designee:
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- Cancer (subject with history of cancer that is in complete remission and not requiring treatment for at least 5 years with the exception of basal cell carcinoma or cervical intraepithelial neoplasia/cervical carcinoma in situ or melanoma in situ superficial skin lesions that have been successfully removed will not be exclusionary);
- Cardiovascular disorders;
- Acute or chronic GI conditions (e.g., gastroesophageal reflux disease, peptic ulcer, colitis, gastric bypass or equivalent) that would interfere with drug tolerance or absorption.
- Respiratory disease.
- Evidence of active infection or febrile illness (e.g., GI, bronchopulmonary, or urinary) within 7 days prior to the first dose of study drug
- Clinically significant infection within 3 months prior to dosing as determined by the PI or designee.
- Positive urine drug or alcohol results at screening or check in.
- Positive urine cotinine at screening.
- Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- Female subjects of childbearing potential.
- Female subjects with a positive pregnancy test or lactating.
- Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
- Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
- QTcB interval is >460 msec or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening
- Estimated creatinine clearance <90 mL/min at screening.
- Unable to refrain from or anticipates the use of:
- Any drug, including prescription and non prescription medications (including herbal products, or vitamin supplements) beginning 14 days prior to the first dose of study drug and throughout the study. Acetaminophen (up to 2 g per 24 hour period) may be permitted during the study; however acetaminophen will not be administered 4 hours before and after dosing. Thyroid hormone replacement medication may be permitted if subject has been on same stable dose for last 3 months prior to first study drug administration.
- Any drugs known to be significant inducers of CYP enzymes and/or P gp, including St. John's Wort, for 28 days prior to the first dose and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/pharmacodynamics interaction with study drug.
- Has been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 28 days prior to the first dose and throughout the study.
- Donation of blood or significant blood loss within 56 days prior to the first dose.
- Plasma donation within 7 days prior to the first dose.
- Participation in another clinical study within 28 days prior to the first dose. The 28 day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label, 2-Period Study to Assess the Effect of Entinostat on the Pharmacokinetics of Midazolam in Healthy Adult Subjects
The purpose of this study is to evaluate the effect of Entinostat on the bioavailability of Midazolam.
The primary objective is to evaluate the effect of a single oral dose of entinostat on the pharmacokinetics (PK) of a single oral dose of midazolam in healthy subjects.
The secondary objective is to evaluate the safety and tolerability of combined administration of entinostat and midazolam in healthy subjects.
Read the detailed description
This is an open label, 2 period, fixed-sequence study.
Twenty-two (22), healthy, adult male subjects will be enrolled; additional subjects may be enrolled to replace discontinued subjects, at the discretion of the Sponsor.
Screening of subjects will occur within 28 prior to the first dose.
On Day 1 of Period 1, a single oral dose of midazolam will be administered followed by PK sampling for midazolam and 1 OH midazolam for 24 hours.
On Day 1 of Period 2, a single oral dose of midazolam will be administered 0.75 hours after a single oral dose of entinostat. Following midazolam dosing on Day 1 of Period 2, PK samples for midazolam and 1 OH midazolam will be taken for 24 hours.
There will be a washout period of at least 7 days between the dosing in Period 1 and entinostat dose in Period 2.
Safety will be monitored throughout the study by repeated clinical and laboratory evaluations.
- Conditions
- Drug Interaction, Healthy Volunteer
- Being tested
- Entinostat, Midazolam
- Keywords
- Healthy Volunteers, Entinostat, Histone Deacetylase Inhibitor, HDAC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntinostatDrug
Also called SNDX-275, MS-275
HDAC (histone deacetylase inhibitor)
MidazolamDrug
benzodiazepine central nervous system (CNS) depressant
| Study group | Role | What they receive |
|---|---|---|
| Midazolam | Other | Treatment A: 2 mg of Midazolam administered - Period 1, Day 1 Treatment B: 2 mg of Midazolam with 5 mg Entinostat (after 14 day minimum washout from Period 1, Day 1) - Period 2, Day 1 Receives: Drug: Entinostat; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK endpoint of AUC0-t (area under the concentration-time curve) for midazolam administered with and without entinostat.
AUC0-t for midazolam and 1 OH midazolam will be computed.
Measured: Pre-dose to 24 hours after dosing
PK endpoint of AUC0-inf (area under the concentration-time curve, from time 0 extrapolated to infinity) for midazolam administered with and without entinostat.
AUC0-inf for midazolam and 1 OH midazolam will be computed
Measured: Pre-dose to 24 hours after dosing
PK endpoint of Cmax (maximum observed concentration) for midazolam administered with and without entinostat.
Cmax for midazolam and 1 OH midazolam will be computed
Measured: Pre-dose to 24 hours after dosing
Secondary outcomes (1)
Incidence of Treatment Emergent Adverse Events (safety and tolerability) of combined administration of entinostat and midazolam in healthy subjects.
Subjects will be followed for adverse events up to 14 days after dose for Period 2, Day 1.
Measured: Pre-dose to 14 days after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start23 May 2017
- Primary completion4 Jun 2017
- Study completion22 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug InteractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Carraher, MD, Principal investigator, Celerion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03187015
- Sponsor's protocol ID
- SNDX-275-0160
- Status last verified
- Aug 2018
- First submitted
- 14 Apr 2017
- Last updated
- 16 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, 2-Period Study to Assess the Effect of Entinostat on the Pharmacokinetics of Midazolam in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT03187015
- Acronym / sponsor ID
- SNDX-275-0160
- Conditions
- Drug Interaction, Healthy Volunteer
- Keywords
- Healthy Volunteers, Entinostat, Histone Deacetylase Inhibitor, HDAC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 May 2017 (actual)
- Primary completion
- 4 Jun 2017 (actual)
- Study completion
- 22 Aug 2017 (actual)
- First posted
- 14 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effect of Entinostat on the bioavailability of Midazolam.
The primary objective is to evaluate the effect of a single oral dose of entinostat on the pharmacokinetics (PK) of a single oral dose of midazolam in healthy subjects.
The secondary objective is to evaluate the safety and tolerability of combined administration of entinostat and midazolam in healthy subjects.
Detailed description
This is an open label, 2 period, fixed-sequence study.
Twenty-two (22), healthy, adult male subjects will be enrolled; additional subjects may be enrolled to replace discontinued subjects, at the discretion of the Sponsor.
Screening of subjects will occur within 28 prior to the first dose.
On Day 1 of Period 1, a single oral dose of midazolam will be administered followed by PK sampling for midazolam and 1 OH midazolam for 24 hours.
On Day 1 of Period 2, a single oral dose of midazolam will be administered 0.75 hours after a single oral dose of entinostat. Following midazolam dosing on Day 1 of Period 2, PK samples for midazolam and 1 OH midazolam will be taken for 24 hours.
There will be a washout period of at least 7 days between the dosing in Period 1 and entinostat dose in Period 2.
Safety will be monitored throughout the study by repeated clinical and laboratory evaluations.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Midazolam | Other | Drug: Entinostat, Drug: MidazolamTreatment A: 2 mg of Midazolam administered - Period 1, Day 1 Treatment B: 2 mg of Midazolam with 5 mg Entinostat (after 14 day minimum washout from Period 1, Day 1) - Period 2, Day 1 |
Who may qualify
- Ages
- 19 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 1. Healthy, adult, male or female (of non childbearing potential only), 19-55 years of age, inclusive, at screening.
- Continuous non smoker who has not used nicotine containing products for at least 3 months prior to the first dose and throughout the study.
- Body mass index (BMI) ≥ 18.5 and ≤ 32 kg/m2 at screening.
- Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. Liver function tests (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP]) and serum bilirubin (total and direct) must be ≤ the upper limit of normal at screening for inclusion. Platelets, hemoglobin and hematocrit must be ≥ than the lower limit of normal at screening for inclusion.
- For a female of non childbearing potential: must have undergone one of the following sterilization procedures, and have official documentation, at least 6 months prior to the first dose:
Key exclusion criteria (28 listed)
- Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit 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 any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose.
- History or presence of hypersensitivity or idiosyncratic reaction to entinostat or drugs with a benzamide structure (e.g., tiapride, remoxipride, clebropride), midazolam, related compounds, or inactive ingredients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntinostatAlso: SNDX-275, MS-275HDAC (histone deacetylase inhibitor) | Drug | Midazolam |
| Midazolambenzodiazepine central nervous system (CNS) depressant | Drug | Midazolam |
Primary outcome
PK endpoint of AUC0-t (area under the concentration-time curve) for midazolam administered with and without entinostat.
Time frame: Pre-dose to 24 hours after dosing
AUC0-t for midazolam and 1 OH midazolam will be computed.
PK endpoint of AUC0-inf (area under the concentration-time curve, from time 0 extrapolated to infinity) for midazolam administered with and without entinostat.
Time frame: Pre-dose to 24 hours after dosing
AUC0-inf for midazolam and 1 OH midazolam will be computed
PK endpoint of Cmax (maximum observed concentration) for midazolam administered with and without entinostat.
Time frame: Pre-dose to 24 hours after dosing
Cmax for midazolam and 1 OH midazolam will be computed
1 secondary outcome
Incidence of Treatment Emergent Adverse Events (safety and tolerability) of combined administration of entinostat and midazolam in healthy subjects.
Time frame: Pre-dose to 14 days after last dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Carraher, MD principal investigator
Celerion
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Entinostat and Midazolam in people with Drug Interaction and Healthy Volunteer, run by Syndax Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK endpoint of AUC0-t (area under the concentration-time curve) for midazolam administered with and without entinostat. (time frame: Pre-dose to 24 hours after dosing). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2018.