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The purpose of this study is to evaluate the effect of entinostat on heart rate and other electrocardiogram (ECG) parameters. This study will also evaluate the safety and tolerability of entinostat, as well as pharmacokinetic and pharmacodynamic parameters.
This is a single center, randomized, placebo-controlled, single dosing schedule, double-blinded study to evaluate the effect of entinostat as compared to placebo on the electrical activity of the heart in patients with advanced solid tumors. Thirty patients will be randomized in a 1:1 ratio to receive either entinostat or placebo. Study treatment will be blinded to patients and the Investigator. ECG analysts will be blinded to the patient, visit, and treatment allocation. Patients will be on study up to 30 days following study drug administration. Total study duration is expected to be 9 months. After completing this study and at the discretion of the Investigator, patients may elect to enroll into a separate continuation study (SNDX-275-0141).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Entinostat | Active Comparator | Participants received a single oral supratherapeutic dose of 15 mg entinostat under fasted conditions. |
|
| Placebo | Placebo Comparator | Participants received a single dose of placebo-matching entinostat under fasted conditions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entinostat | Drug | Single, supratherapeutic dose of entinostat given orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in Heart Rate (HR) | Heart rate measured in beats per minute (bpm). | Baseline (pre-dose) through 24 hours post-dose |
| Change from Baseline in Electrocardiogram Procedures | Change from baseline in QT interval corrected for heart rate (Qtc), PR interval (PR) and QRS complex (QRS). | Baseline (pre-dose) through 24 hours post-dose |
| Change from Baseline in T-Cell Morphology | Baseline (pre-dose) through 24 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Treatment-emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE is an AE that occurs after the first dose of study drug. A SAE is defined as any AE that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Immune Regulatory Cells after a Single Dose of Entinostat, when given at a Supratherapeutic Dose, Relative to Placebo Control | Pre-dose through 14 days post-dose | |
| Variability and Changes in Protein Lysine Acetylation in Peripheral Blood Cells after a Single Dose of Entinostat, when given at a Supratherapeutic Dose and Examine the Underlying Biological Variation |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Meyers, MD, PhD | Syndax Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The START Center for Cancer Care | San Antonio | Texas | 78229 | United States |
Data will be reviewed throughout the study by the sponsor, Contract Research Organization (CRO) assisting with Serious Adverse Event (SAE) management, and routine monitoring to safeguard the interests of trial patients and to assess the safety of the interventions administered during the trial.
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| Placebo | Drug | Single dose of placebo-matching entinostat (containing inactive ingredients matching the appearance of the active product). |
|
| First dose through 30 days post-dose or through resolution of acute toxicities (Up to 31 days) |
| Number of Participants with Clinically Significant Abnormalities in Laboratory Values Reported as a TEAE | Standard safety laboratory tests included Chemistry, Hematology. Any hematologic or clinical chemistry abnormality considered by the investigator to be clinically significant was reported as a TEAE. | Baseline (pre-dose) through 14 days post-dose or 30 day safety follow-up visit (if applicable) |
| Change from Baseline in Vital Signs | Vital signs included temperature, pulse, blood pressure, and respiration rate | Baseline (pre-dose) through 14 days post-dose or 30 day safety follow-up visit (if applicable) |
| Change from Baseline in ECG Values | A 12-lead continuous ECG recording (via a Holter) was recorded on Day 1 for 25 hours. Safety ECGs were read and interpreted by the Investigator on-site for the purpose of safety monitoring and were transmitted electronically to the central ECG laboratory for clinical interpretation by a cardiologist | Baseline ()pre-dose through 14 days post-dose or 30 day safety follow-up visit (if applicable) |
| Change from Baseline in QTc | Pre-dose through 24 hours post-dose |
| Cmax (Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose | Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose |
| Tmax (Time of Maximum Plasma Concentration) of Entinostat when given as a Single Supratherapeutic Dose | Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose |
| AUC0-24 (Area under the Plasma Concentration-time Curve from Time Zero to 24 hours) of Entinostat when given as a Single Supratherapeutic Dose | Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose |
| AUC0-t (Area under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration) of Entinostat when given as a Single Supratherapeutic Dose | Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose |
| AUC0-inf (Area under the Plasma Concentration-time Curve from 0-time Extrapolated to Infinity) of Entinostat when given as a Single Supratherapeutic Dose | Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose |
| t1/2 (Elimination Half-life and Apparent Plasma Terminal Phase Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose | Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose |
| λz (Terminal Elimination Rate Constant) of Entinostat when given as a Single Supratherapeutic Dose | Pre-dose and multiple time-points through 24 hours post-dose and 14 days post-dose |
| Pre-dose through 14 days post-dose |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D008171 | Lung Diseases |
| D001943 | Breast Neoplasms |
| D001941 | Breast Diseases |
| D007680 | Kidney Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D004066 | Digestive System Diseases |
| D004700 | Endocrine System Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C118739 | entinostat |
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