NL-OMON48219已完成2 期
Randomized, Double-blind, Placebo-controlled, Two-Part, Adaptive Design Study of Safety, Tolerability, Preliminary Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of MYK-491 in Patients with Stable Heart Failure with Reduced Ejection Fraction - Heart Failure study in patients with reduced heart function
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 至 99（—）
入选标准
- •This study is to be performed in patients with HFrEF due to any etiology. Each
- •patient must meet the following criteria to be included in this study:
- •1. Able to understand and comply with the study procedures, understand the
- •risks involved in the study, and provide written informed consent according to
- •federal, local, and institutional guidelines before the first study-specific
- •2. Men or women 18 to 80 years of age at the Screening visit.
- •3. Body mass index (BMI) 18 to 40 kg/m2, inclusive, at the Screening visit and
- •all required assessments can be reliably performed.
- •4. Sinus rhythm or stable atrial pacing with mean resting heart rate (HR) 50-95
- •beats per minute (bpm), inclusive. (Patient will be ineligible to dose if, on
- •Day 1, the predose HR measurement is * 95 bpm. Heart rate is the mean of 3
- •measurements taken 1 minute apart. A single measurement would not make a
- •patient ineligible).
- •5. Has stable, chronic HFrEF of moderate severity as defined by all of the
- •* For the first 3 patients in each multiple-ascending dose (MAD) cohort testing
- •a new (higher) daily dose: documented LVEF 25% to 35% during Screening (as
- •confirmed by ECHO Central Lab)
- •* For other patients in the MAD Cohorts (and all patients in SAD Cohorts):
- •documented LVEF 15% to 35% during Screening (as confirmed by ECHO Central Lab)
- •* LVEF must be confirmed with second screening ECHO to be performed at least 7
- •days after initial screening ECHO. Results of both must meet inclusion
- •criteria and must be received from core lab prior to dosing. In the event of
- •extended screening windows due to SRC reviews, effort should be made to ensure
- •second ECHO is near planned time of randomization.
- •* Chronic medication for the treatment of heart failure consistent with current
- •guidelines that has been given at stable doses for * 2 weeks with no plan to
- •modify during the study. This includes treatment with at least one of the
- •following unless not tolerated or contraindicated: beta-blocker, angiotensin
- •converting enzyme (ACE) inhibitor/angiotensin receptor blocker
- •(ARB)/angiotensin receptor neprilysin inhibitor (ARNI)
- •6. Female patients must not be pregnant or lactating. Male patients (including
- •men who have had vasectomies), as there may be a risk of drug being secreted in
- •the ejaculate, should use barrier methods for the duration of the study and for
- •3 months after the last dose of study medication. All patients, if sexually
- •active, must be using one of the following highly-effective birth control
- •methods from the Screening visit through 3 months after the last dose of
- •investigational medicinal product (IMP):
- •* Hormonal contraception associated with inhibition of ovulation, intrauterine
- •device (IUD), or intrauterine hormone-release system (IUS) plus barrier (eg,
- •male using condom or female using diaphragm or cervical cap).
- •* Vasectomy plus barrier.
- •* Female is surgically sterile for 6 months or postmenopausal for 1 year.
- •Permanent sterilization includes hysterectomy, bilateral oophorectomy,
- •bilateral salpingectomy, and/or documented bilateral tubal occlusion at least 6
- •months prior to Screening. Females are considered postmenopausal if they have
- •had amenorrhea for at least 1 year or more following cessation of all exogenous
- •hormonal treatments, and follicle-stimulating hormone (FSH) level
排除标准
- •Patients who meet any of the following criteria will be excluded from the study.
- •1. Inadequate echocardiographic acoustic windows.
- •2. Any of the following ECG abnormalities (a) QTcF > 480 ms (Fridericia*s
- •correction, not attributable to pacing or prolonged QRS duration, average of
- •triplicate Screening ECGs) or (b) second-degree atrioventricular block type II
- •or higher in a patient who has no pacemaker.
- •3. Hypersensitivity to MYK 491 or any of the components of the MYK 491
- •formulation.
- •4. Active infection as indicated clinically as determined by the investigator.
- •5. History of malignancy of any type within 5 years prior to Screening, with
- •the exception of the following surgically excised cancers occurring more than 2
- •years prior to Screening: in situ cervical cancer, nonmelanomatous skin
- •cancers, ductal carcinoma in situ, and nonmetastatic prostate cancer.
- •6. Positive serologic test at Screening for infection with human
- •immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus
- •7. Hepatic impairment (defined as alanine aminotransferase [ALT]/ aspartate
- •aminotransferase [AST] > 3 times upper limit of normal [ULN] and/or total
- •bilirubin [TBL] > 2 times ULN).
- •8. Severe renal insufficiency (defined as current estimated glomerular
- •filtration rate [eGFR] < 30 mL/min/1.73m2 by simplified Modification of Diet in
- •Renal Disease equation [sMDRD]).
- •9. Serum potassium < 3.5 or > 5.5 mEq/L.
- •10. Any persistent out-of-range safety laboratory parameters (chemistry,
- •hematology, urinalysis), considered by the investigator and medical monitor to
- •be clinically significant.
- •11. History or evidence of any other clinically significant disorder,
- •condition, or disease (including substance abuse) that, in the opinion of the
- •investigator or MyoKardia physician would pose a risk to patient safety or
- •interfere with the study evaluation, procedures, completion, or lead to
- •premature withdrawal from the study.
- •12. Participated in a clinical trial in which the patient received any
- •investigational drug (or is currently using an investigational device) within
- •30 days prior to Screening, or at least 5 times the respective elimination
- •half-life (whichever is longer).
- •13. Previous participation in a clinical trial with MYK-491, with the exception
- •that patients that participated or were screen failures in one part of this
- •trial may participate in the other part, ie patients may enroll in Part 1 (SAD)
- •followed by Part 2 (MAD) or Part 2 (MAD) followed by Part 1 (SAD), with the
- •following caveats:
- •* If the patient has an ongoing adverse event (AE), has had a serious adverse
- •event (SAE), or has met any stopping criteria, the investigator should contact
- •the Sponsor prior to enrolling the patient in a subsequent cohort.
- •* Patients must have at least 1 week washout after the end of MAD dosing prior
- •to SAD dosing, or at the end of SAD dosing prior to MAD dosing.
- •* Patients do not need to rescreen if MAD screening occurred within 12 weeks of
- •the first SAD dosing, or if SAD screening occurred within 12 weeks of the first
- •MAD dosing. Investigators should verify that patients are clinically stable and
- •no exclusions have occurred during the interim; if > 12 weeks have elapsed or
- •there is clinical instability, then patients should be rescreened.
- •14. Unable to comply with the study rest
研究者
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