NCT03486080已完成2 期
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study of Dutogliptin in Combination With Filgrastim in Early Recovery Post-Myocardial Infarction
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 12
- 主要终点
- Safety assessment of the number of Grade 3 and 4 treatment emergent AEs or serious AEs (SAEs) as assessed by CTCAE v4.0.AEs (SAEs) as assessed by CTCAE v4.0.
研究概览
简要总结
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study of Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction
详细描述
Dutogliptin 60 mg administered by twice daily subcutaneous (SC) injection for 14 days in combination with a fixed standard dose of filgrastim (10 µg/kg) administered SC daily for 5 days. This study will be conducted in adults with ST-elevation myocardial infarction (STEMI) with successful revascularization following percutaneous coronary intervention (PCI) and stent implantation.
Primary Objective
• To evaluate the safety and tolerability of dutogliptin in combination with filgrastim in subjects with STEMI compared with placebo
Secondary Objectives
- To assess preliminary efficacy of dutogliptin in combination with filgrastim in subjects with STEMI compared with placebo as determined by cardiac magnetic resonance imaging (cMRI)
- To determine the pharmacokinetics (PK) of dutogliptin in a subset of the study population
- To establish the pharmacodynamics (PD) of dutogliptin (plasma DPP4 activity) in a subset of the study population
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinded placebo controlled
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female born between 1933 and
- •Body weight <96 kg (212 lb).
- •Able to provide written informed consent, including signing and dating the informed consent form (ICF).
- •Diagnosis of STEMI (defined as new ST-segment elevation at the J point of at least 2 continuous leads of >2 mm [0.2 mV] in men or >1.5 mm [0.1 mV] in women in leads V2 and V3 OR >1 mm in any other contiguous precordial leads or the limb leads [for both men and women]) with PCI (bare metal or drug-eluting stent) and Thrombolysis in Myocardial Infarction flow grade 2 or 3 occurring >2 hours and <24 hours after symptom onset.
- •LVEF ≤45% obtained by cECHO performed within 36 hours post-stent placement.
- •Receiving standard medical therapy for post-MI treatment, according to local procedures and Principal Investigator discretion
- •Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and an additional negative urine pregnancy test prior to the first dose of IMP unless regulated differently by national legislation.
- •Sexually active female subjects of childbearing potential (i.e., women who are not postmenopausal or who have not had a bilateral oophorectomy, hysterectomy, or tubal ligation) and all male subjects (who have not been surgically sterilized by vasectomy) must agree to use effective contraception during the study.
- •Exclusion criteria
- •Previous MI prior to Screening.
- •Complex peri/post-MI clinical course, including arrhythmias, cardiogenic shock, pulmonary edema requiring mechanical ventilation, or requirement for vasopressor medications.
- •Significant pre-existing cardiomyopathy with known LVEF ≤45% or moderate to severe mitral or aortic valvular disease.
- •Amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
- •Existing heart transplant.
- •Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.
- •Uncontrolled hypertension (systolic >180 mmHg or diastolic >120 mmHg).
- •Treatment with any DPP4 inhibitors (e.g., alogliptin, linagliptin, vildagliptin, saxagliptin, sitagliptin) or G-CSF medication (e.g., filgrastim, lenograstim, pegfilgrastim, lipegfilgrastim) within 4 months prior to Randomization.
- •Contraindication to treatment with filgrastim, including known allergy to filgrastim or other G-CSF medication.
- •Anemia defined as hemoglobin <9 g/dL prior to Randomization.
- •Thrombocytosis (platelets >500 k/µL).
- •Known positive serology for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- •Alanine aminotransferase (ALT) concentrations >3 times the upper limit of normal (ULN) or bilirubin >2 x ULN prior to Randomization, according to local laboratory assessments.
- •History of cirrhosis and Child-Pugh score B or C.
- •Current fever greater than 101.4 °F (38.6 °C) or recent systemic infection within 2 weeks prior to Randomization.
- •Contraindication to cMRI procedure, including prior implantable cardioverter defibrillator placement, known reaction to gadolinium, claustrophobia, non-MRI-compatible, cochlear implant, morbid obesity, or presence of ferromagnetic material including shunts, shrapnel, penile prostheses, or blood vessel coil.
- •Pregnant, planning to become pregnant, or nursing female subjects.
- •Autoimmune disease requiring immunosuppressive therapy or chronic steroid treatment >5 mg/day prednisolone or equivalent.
- •Significant renal impairment defined as estimated glomerular filtration rate <45 mL/min/1.73 m2, using the Chronic Kidney Disease Epidemiology Collaboration equation.
- •Active neoplasm requiring surgery, chemotherapy, or radiation within the prior 12 months (subjects with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12 months prior to Screening with no detectable recurrence are allowed).
- •Malignant hematological disease, i.e., chronic myeloid leukemia or myelodysplastic syndrome.
- •History of cerebrovascular accident or transient ischemic attack in the past 6 months.
- •History of pneumonia in the last 4 weeks.
- •History of any significant medical or psychiatric disorder that in the opinion of the investigator would make the subject unsuitable for participation in the study.
- •Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) or treatment with an investigational biologic drug within 6 weeks prior to randomization.
- •Participation in another concurrent clinical trial involving a therapeutic intervention (participation in observational studies and/or registry studies is permitted).
- •Unable or unwilling to comply with the requirements of the study.
- •Subject and/or an immediate family member is an employee of the investigational site directly affiliated with this study, the sponsor or the contract research organization.
- •Considered by the investigator to be unsuitable to participate in the study for any other reason.
- •Persons who are in an institution as a result of an administrative or judicial order, or soldiers.
- •History of alcohol or drug abuse.
排除标准
- 未提供
研究组 & 干预措施
Dutogliptin/filgrastim combination
Active Comparator
Twice daily SC injections of 60 mg dutogliptin tartrate for 14 days in combination with 10 µg/kg filgrastim injectable product for 5 days
干预措施: Dutogliptin Tartrate (Drug)
Dutogliptin/filgrastim combination
Active Comparator
Twice daily SC injections of 60 mg dutogliptin tartrate for 14 days in combination with 10 µg/kg filgrastim injectable product for 5 days
干预措施: Filgrastim Injectable Product (Drug)
Placebo control
Placebo Comparator
Twice daily dutogliptin SC placebos for 14 days in combination with matching filgrastim SC placebos for 5 days
干预措施: Placebos (Drug)
结局指标
主要结局
Safety assessment of the number of Grade 3 and 4 treatment emergent AEs or serious AEs (SAEs) as assessed by CTCAE v4.0.AEs (SAEs) as assessed by CTCAE v4.0.
时间窗: 90 days
Assess the tolerability of a combination of dutogliptin and filgrastim
次要结局
- Cardiovascular efficacy LVESV(90 days)
- Cardiovascular motion(90 days)
- Pharmacodynamics (PD)(14 days)
- Cardiovascular efficacy LVEF(90 days)
- Cardiovascular efficacy LVEDV(90 days)
- Cardiovascular tissue damage reduction(90 days)
- Pharmacokinetics (PK)(14 days)
- Cardiovascular LFM(90 days)
研究者
研究点 (12)
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