Renal ImpairmentPhase 1NCT03192111
A Study to Evaluate the Pharmacokinetics of Entinostat in Adult Subjects With Normal and Impaired Renal Function
A Phase 1 study testing Entinostat in people with Renal Impairment and Healthy Volunteer, run by Syndax Pharmaceuticals at 3 sites in United States.
Trial summary
This purpose of this study is to evaluate the effects of a single dose of entinostat on subjects with varying levels of renal impairment. The primary objective of this study is to evaluate the pharmacokinetics of a single dose of entinostat in adult subjects with mild, moderate and severe renal impairment compared to… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Renal Impairment, Healthy Volunteer
- What is being tested?
- Entinostat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- 27 Jul 2017to 23 Nov 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All Subjects:
- Adult male or female (of non childbearing potential only), at least 18 years of age, at screening.
- BMI ≥ 18.5 to ≤ 40.0 kg/m2, at screening.
- Subject is a non-smoker or moderate smoker (≤ 10 cigarettes/day or the equivalent). Subject must agree to consume no more than 10 cigarettes or equivalent/day from the time of screening and throughout the period of PK sample collection.
- Females must be of non childbearing potential and must have undergone one of the following sterilization procedures, and have official documentation, at least 6 months prior to dosing:
- hysteroscopic sterilization;
Show all 24Show fewer
- bilateral tubal ligation or bilateral salpingectomy;
- hysterectomy;
- bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to dosing 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 dosing of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to dosing of study drug. A male who has been vasectomized less than 4 months prior to dosing must follow the same restrictions as a non vasectomized male).
- If male, must agree not to donate sperm from dosing until 90 days after dosing of study drug.
- Understands the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol.
- Mild, Moderate, and Severe Renal Impaired Subjects:
- Baseline health is judged to be stable based on medical history, laboratory profiles, vital signs, or ECGs at screening, as deemed by the PI. Subjects with any clinical laboratory results outside normal ranges may be enrolled if deemed appropriate in the opinion of the PI.
- For subjects with mild RI only: Baseline eGFR 60 89 mL/min/1.73m2, inclusive, based on the MDRD equation at screening defined as follows:
- eGFR = 175 x (Scr,std)-1.154 x (Age)-0.203 Scr, std: serum creatinine (mg/dL) measured with a standardized assay. For females, multiply result by 0.742; if African American, multiply result by 1.212.
- For subjects with moderate RI only: Baseline eGFR 30 - 59 mL/min/1.73m2, inclusive, based on the MDRD equation at screening as described above.
- For subjects with severe RI only: Baseline eGFR 29 mL/min/1.73m2 or less based on the MDRD equation at screening as described above.
- Subject has had no clinically significant change in renal status at least 1 month prior to study medication administration and is not currently or has not previously been on hemodialysis.
- Matched Healthy Control Subjects 8. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. Subjects with any clinical laboratory results outside normal ranges may be enrolled if deemed appropriate in the opinion of the PI.
- 9. Has eGFR ≥ 90 mL/min/1.73m2, based on the MDRD equation at screening defined as follows: eGFR = 175 x (Scr,std)-1.154 x (Age)-0.203 Scr, std: serum creatinine (mg/dL) measured with a standardized assay. For females, multiply result by 0.742; if African American, multiply result by 1.212.
- Actual creatinine clearance, as determined by a 24-hour urine collection, may be used in place of or in conjunction with the MDRD equation, at the PI's discretion. Subjects who have an actual or estimated creatinine clearance up to 10% below 90 mL/min/1.73m2 may be enrolled in the study at the discretion of the PI.
- 10. The age of individual healthy adult male and female subjects is aimed to be within the range of the mean age ± 10 years of the mild, moderate and severe RI subjects. In the event that these subjects do not match the mean for age in the severe RI cohort, additional healthy subjects (up to 8) will be enrolled using the same criteria.
- 11. The BMI of individual healthy adult male and female subjects is aimed to be within the range of the mean BMI ± 20 % of the mild, moderate and severe RI subjects. In the event that these subjects do not match the mean for BMI in the severe RI cohort, additional healthy subjects (up to 8) will be enrolled using the same criteria.
Who cannot join
- All Subjects:
- 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 hypersensitivity or idiosyncratic reaction to the study drug or drugs with a benzamide structure (e.g., tiapride, remoxipride, clebropride), 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:
Show all 32Show fewer
- Cancer (subject with history of cancer that is in complete remission and not requiring treatment for at least 5 years, 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).
- Active cardiovascular disorders (no history of myocardial infarction within 6 months of dosing, no stents or bypass within 6 months of dosing, ≥ Class 2 congestive heart failure).
- Acute or chronic GI conditions (e.g., peptic ulcer, colitis, gastric bypass or equivalent) that would interfere with drug tolerance or absorption; subjects with cholecystectomy or uncomplicated gallbladder for over 1 year of dosing would be allowed.
- Clinically significant infection within 1 month prior to dosing as determined by the PI or designee.
- Female subjects of childbearing potential, pregnant or lactating subjects.
- Positive results for the urine/saliva drug screen or for the urine/breath alcohol screen at screening or check-in unless the positive drug screen is due to prescription drug use and is approved by the PI and Sponsor.
- Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
- Unable to refrain from or anticipates the use of:
- Any drug known to be metabolized by CYP1A2 or CYP2C8, or to be a strong or moderate inhibitor of P gp or breast cancer resistance protein (BCRP) for 14 days prior to dosing and throughout the study. Use of weak inhibitors may be deemed acceptable following consultation with the Sponsor Medical Monitor and the PI. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/pharmacodynamic interaction with study drug.
- Any medication or substance (including prescription or over-the-counter, including herbal products, natural or herbal supplements) which cannot be discontinued at least 14 days prior to dosing and throughout the study. Subjects who are taking medications for stable diseases for at least ~2 weeks for subjects with severe RI or ~1 month for mild and moderate renal impaired subjects (or 5 half-lives of the compound, whichever is longer) prior to dosing will be allowed to participate in the study at the discretion of the PI and following consultation with the Sponsor Medical Monitor. See Section 10.4.2 for additional details on allowable and prohibited concomitant therapy.
- Seated heart rate is equal to or lower than 40 bpm or higher than 99 bpm at screening.
- Subject has had a renal transplant or has had nephrectomy.
- 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 dosing and throughout the study.
- Donation of blood or significant blood loss within 56 days prior to dosing.
- Plasma donation within 7 days prior to dosing.
- Participation in another clinical study within 28 days prior to dosing. The 28 day window will be derived from the date of dosing.
- Mild, Moderate, and Severe Renal Impaired Subjects:
- History or presence of alcoholism or drug abuse within the past 6 months prior to dosing.
- Seated blood pressure is less than 90/40 mmHg or greater than 180/105 mmHg at screening.
- PR interval > 240 msec, QRS > 140 msec at screening.
- QTcF interval is >490 msec or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening.
- Has rapidly fluctuating renal function as determined by historical measurements. Rapidly fluctuation renal function is defined as creatinine clearance that differs by more than 30% within 3 months of the screening eGFR determination. If historical measurements are not available, then the 2 measurements will be used to demonstrate stability.
- Healthy Subjects:
- 20. History or presence of alcoholism or drug abuse within the past 2 years prior to dosing.
- 21. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
- 22. PR interval > 220 msec or QRS > 120 msec at screening. 23. QTcF interval is > 450 msec or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
New Orleans Center for Clinical Research
Knoxville, Tennessee, 37920
Clinical Pharmacology of Miami
Miami, Florida, 33014
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
Official title: A Phase 1, Open-Label, Parallel-Cohort, Single-Dose Study to Evaluate the Pharmacokinetics of Entinostat in Adult Subjects With Normal and Impaired Renal Function
This purpose of this study is to evaluate the effects of a single dose of entinostat on subjects with varying levels of renal impairment.
The primary objective of this study is to evaluate the pharmacokinetics of a single dose of entinostat in adult subjects with mild, moderate and severe renal impairment compared to healthy mean-matched subjects.
The secondary objective of this study is to evaluate the safety and tolerability of entinostat in adult subjects with mild, moderate, and severe renal impairment and in healthy mean-matched adult subjects.
- Conditions
- Renal Impairment, Healthy Volunteer
- Being tested
- Entinostat
- Keywords
- Healthy Volunteers, Mild Renal Impairment, Moderate Renal Impairment, Severe Renal Impairment, Entinostat, Histone Deacetylase Inhibitor, HDAC
- Medical subject headings
- Renal Insufficiency
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
| Study group | Role | What they receive |
|---|---|---|
| Mild Renal Impairment | Experimental | Subjects with mild renal impairment Receives: Drug: Entinostat |
| Moderate Renal Impairment | Experimental | Subjects with moderate renal impairment Receives: Drug: Entinostat |
| Severe Renal Impairment | Experimental | Subjects with severe renal impairment Receives: Drug: Entinostat |
| Healthy Subjects | Experimental | Healthy volunteers mean-matched to the mild, moderate, and severe renal impairment patients Receives: Drug: Entinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate AUC0-t (area under the concentration-time curve) for entinostat in subjects with varying degrees of renal impairment versus healthy matched subjects.
AUC0-t will be computed for all subjects
Measured: Pre-dose through Day 22
To evaluate AUC0-inf (area under the concentration-time curve, from time 0 to infinity) for entinostat in subjects with varying degrees of renal impairment versus healthy matched subjects.
AUC0-inf will be computed for all subjects
Measured: Pre-dose through Day 22
To evaluate Cmax (maximum observed concentration) for entinostat in subjects with varying degrees of renal impairment versus healthy matched subjects.
Cmax will be computed for all subjects
Measured: Pre-dose through Day 22
Secondary outcomes (1)
Incidence of Treatment Emergent Adverse Events (safety and tolerability) of entinostat in subjects with varying degrees of renal impairment and healthy mean-matched healthy subjects
Subjects will be followed for adverse events up to 14 days after the last PK sample is collected.
Measured: Pre-dose to 14 days after last PK sample
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2017
- Study start27 Jul 2017
- Primary completion23 Nov 2017
- Study completion23 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal ImpairmentStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03192111
- Sponsor's protocol ID
- SNDX-275-0190
- Status last verified
- Apr 2018
- First submitted
- 15 Jun 2017
- Last updated
- 13 Apr 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 13 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Parallel-Cohort, Single-Dose Study to Evaluate the Pharmacokinetics of Entinostat in Adult Subjects With Normal and Impaired Renal Function
- ClinicalTrials.gov ID
- NCT03192111
- Acronym / sponsor ID
- SNDX-275-0190
- Conditions
- Renal Impairment, Healthy Volunteer
- Keywords
- Healthy Volunteers, Mild Renal Impairment, Moderate Renal Impairment, Severe Renal Impairment, Entinostat, Histone Deacetylase Inhibitor, HDAC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 27 Jul 2017 (actual)
- Primary completion
- 23 Nov 2017 (actual)
- Study completion
- 23 Nov 2017 (actual)
- First posted
- 19 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.
This purpose of this study is to evaluate the effects of a single dose of entinostat on subjects with varying levels of renal impairment.
The primary objective of this study is to evaluate the pharmacokinetics of a single dose of entinostat in adult subjects with mild, moderate and severe renal impairment compared to healthy mean-matched subjects.
The secondary objective of this study is to evaluate the safety and tolerability of entinostat in adult subjects with mild, moderate, and severe renal impairment and in healthy mean-matched adult subjects.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Mild Renal Impairment | Experimental | Drug: EntinostatSubjects with mild renal impairment |
| Moderate Renal Impairment | Experimental | Drug: EntinostatSubjects with moderate renal impairment |
| Severe Renal Impairment | Experimental | Drug: EntinostatSubjects with severe renal impairment |
| Healthy Subjects | Experimental | Drug: EntinostatHealthy volunteers mean-matched to the mild, moderate, and severe renal impairment patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Adult male or female (of non childbearing potential only), at least 18 years of age, at screening.
- BMI ≥ 18.5 to ≤ 40.0 kg/m2, at screening.
- Subject is a non-smoker or moderate smoker (≤ 10 cigarettes/day or the equivalent). Subject must agree to consume no more than 10 cigarettes or equivalent/day from the time of screening and throughout the period of PK sample collection.
- Females must be of non childbearing potential and must have undergone one of the following sterilization procedures, and have official documentation, at least 6 months prior to dosing:
- 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 dosing of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to dosing of study drug. A male who has been vasectomized less than 4 months prior to dosing must follow the same restrictions as a non vasectomized male).
Key exclusion criteria (32 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 hypersensitivity or idiosyncratic reaction to the study drug or drugs with a benzamide structure (e.g., tiapride, remoxipride, clebropride), 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:
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 | Healthy Subjects, Mild Renal Impairment, Moderate Renal Impairment, Severe Renal Impairment |
Primary outcome
To evaluate AUC0-t (area under the concentration-time curve) for entinostat in subjects with varying degrees of renal impairment versus healthy matched subjects.
Time frame: Pre-dose through Day 22
AUC0-t will be computed for all subjects
To evaluate AUC0-inf (area under the concentration-time curve, from time 0 to infinity) for entinostat in subjects with varying degrees of renal impairment versus healthy matched subjects.
Time frame: Pre-dose through Day 22
AUC0-inf will be computed for all subjects
To evaluate Cmax (maximum observed concentration) for entinostat in subjects with varying degrees of renal impairment versus healthy matched subjects.
Time frame: Pre-dose through Day 22
Cmax will be computed for all subjects
1 secondary outcome
Incidence of Treatment Emergent Adverse Events (safety and tolerability) of entinostat in subjects with varying degrees of renal impairment and healthy mean-matched healthy subjects
Time frame: Pre-dose to 14 days after last PK sample
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 13 Apr 2018.
- Individual participant dataSharing planned: No
Related trials for Renal Impairment
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites 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 in people with Renal Impairment and Healthy Volunteer, run by Syndax Pharmaceuticals at 3 sites 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 24 inclusion and 32 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 13 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
To evaluate AUC0-t (area under the concentration-time curve) for entinostat in subjects with varying degrees of renal impairment versus healthy matched subjects. (time frame: Pre-dose through Day 22). 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 13 Apr 2018.