NCT01766817已完成2 期
Safety and Efficacy of a Lysophosphatidic Acid Receptor Antagonist in Idiopathic Pulmonary Fibrosis
Bristol-Myers Squibb53 个研究点 分布在 2 个国家目标入组 325 人开始时间: 2013年1月31日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 325
- 试验地点
- 53
- 主要终点
- Change From Baseline in Forced Vital Capacity (FVC) Rate to Week 26
研究概览
简要总结
The purpose of this study is to determine if study drug (BMS-986020) dose of 600 mg once daily or 600 mg twice daily for 26 weeks compared with placebo will reduce the decline in forced vital capacity (FVC) and will be well tolerated in subjects with idiopathic pulmonary fibrosis (IPF).
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are between the ages of 40 and 90 years, inclusive, at randomization.
- •Have clinical symptoms consistent with IPF.
- •Have first received a diagnosis of IPF less than 6 years before randomization. The date of diagnosis is defined as the date of the first available imaging or surgical lung biopsy consistent with IPF/UIP.
- •Have a diagnosis of usual interstitial pulmonary fibrosis (UIP) or IPF by HRCT or surgical lung biopsy (SLB).
- •Extent of fibrotic changes (honeycombing, reticular changes) greater than the extent of emphysema on HRCT scan.
- •Have no features supporting an alternative diagnosis on transbronchial biopsy, BAL, or SLB, if performed.
- •Have percent predicted post-bronchodilator FVC between 45% and 90%, inclusive, at screening.
- •Have a change in post-bronchodilator FVC (measured in liters) between screening and day 1 that is less than a 10% relative difference, calculated as: the absolute value of 100% * (screening FVC (L) - day 1 FVC (L)) / screening FVC (L).
- •Have carbon monoxide diffusing capacity (DLCO) between 30% and 80% (adjusted for hemoglobin and altitude), inclusive, at screening.
- •Have no evidence of improvement in measures of IPF disease severity over the preceding year, in the investigator's opinion.
- •Be able to walk 150 meters or more at screening.
- •Demonstrate an exertional decrease in oxygen saturation of 2 percentage points or greater at screening (may be performed with supplemental oxygen titrating to keep oxygen saturation levels >88%).
- •Are able to understand and sign a written informed consent form.
- •Are able to understand the importance of adherence to study treatment and the study protocol and are willing to comply with all study requirements, including the concomitant medication restrictions, throughout the study.
- •Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must use acceptable method(s) of contraception. The individual methods of contraception and duration should be determined in consultation with the investigator. WOCBP must follow instructions for birth control when the half-life of the investigational drug is less than 24 hours, contraception should be continued for a period of 30 days after the last dose of investigational product.
- •Women must have a negative urine pregnancy test within 24 hours prior to the start of investigational product.
- •Women must not be breastfeeding.
- •Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men that are sexually active with WOCBP must follow instructions for birth control when the half-life of the investigational drug is less than 24 hours, contraception should be continued for a period of 90 days after the last dose of investigational product.
- •Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men do not require contraception.
排除标准
- •Target Disease Exclusions
- •Has significant clinical worsening of IPF between screening and day 1 (during the screening process), in the opinion of the investigator.
- •Has forced expiratory volume in 1 second (FEV1)/FVC ratio less than 0.8 after administration of bronchodilator at screening.
- •Has bronchodilator response, defined by an absolute increase of 12% or greater and an increase of 200 mL in FEV1 or FVC or both after bronchodilator use compared with the values before bronchodilator use at screening.
- •Medical History and Concurrent Diseases
- •Has a history of clinically significant environmental exposure known to cause pulmonary fibrosis, including, but not limited to, drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds.
- •Has a known explanation for interstitial lung disease, including, but not limited to, radiation, drug toxicity, sarcoidosis, hypersensitivity, pneumonitis, bronchiolitis, obliterans, organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer.
- •Has a clinical diagnosis of any connective tissue disease, including, but not limited to, scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and undifferentiated connective tissue disease.
- •Currently has clinically significant asthma or chronic obstructive pulmonary disease.
- •Has clinical evidence of active infection, including, but not limited to, bronchitis, pneumonia, sinusitis, urinary tract infection, and cellulitis.
- •Has any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 2 years. This does not include minor surgical procedures for localized cancer (e.g., basal cell carcinoma).
- •Has any condition other than IPF that, in the opinion of the investigator, is likely to result in the death of the subject within the next 2 years.
- •Has a history of end-stage liver disease.
- •Has a history of end-stage renal disease requiring dialysis.
- •Has a history of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months, including, but not limited to, the following: i. Unstable angina pectoris or myocardial infarction ii. Congestive heart failure requiring hospitalization iii. Uncontrolled clinically significant arrhythmias
- •Has any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of BMS-
- •Has a history of alcohol or substance abuse in the past 2 years.
- •Has a family or personal history of long QT syndrome and/or Torsades de Pointes (polymorphic ventricular tachycardia).
- •Has used any of the excluded medications per Appendix 1 of the Protocol, which includes, but is not limited to:
- •current treatment with pirfenidone or nintedanib
- •use of over-the-counter medications and herbal preparations, within 4 weeks before study drug administration except those medications cleared by the BMS medical monitor
- •For subjects taking statins, there are restrictions on the maximum allowable doses for statins listed below. If subjects are currently taking statins and their doses are higher than those mentioned below, please reduce the dose to the maximum allowable dose.
- •Additionally, if subjects are on statins and ready to start dosing, these subjects should limit statin doses by maximal allowable dose or lower for at least 5 days prior to the first BMS-986020 dosing. Shorter durations may be considered in select cases after discussion with the medical monitor.
- •Maximum allowable dose for statins:
- •Simvastatin 20 mg QD
- •Pitavastatin 2 mg QD
- •Atorvastatin 40 mg QD
- •Pravastatin 40 mg QD
- •Rosuvastatin 20 mg QD
- •Lovastatin 40 mg QD
- •Fluvastatin 40 mg QD
- •Prednisone is allowed up to a maximum of 15 mg po daily
- •Pirfenidone or nintedanib dosing for a maximum of 3 months in the prior 12 months is permitted with a 4 week washout period prior to dosing with BMS-
- •Physical and Laboratory Test Findings
- •Has any of the following liver-function test criteria above the specified limits: total bilirubin >1.5 x ULN, excluding subjects with Gilbert's syndrome; aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) greater than 3 x ULN; alkaline phosphatase greater than 2.5 x ULN.
- •Has creatinine clearance less than 30 mL/minute, calculated using the Cockcroft-Gault formula.
- •Has ECG result with a QT interval by Fridericia's correction (QTcF) of 500 msec or greater or an uncorrected QT of 500 msec or greater at screening. Note: For subjects with a machine read QT interval of >500 msec, if their heart rate is > 100 bpm, the machine read QT interval (either corrected or not) may not be accurate. If the investigator is uncertain about the QT abnormality, it is recommended that ECGs be over-read by a cardiologist. The manually read QT interval by a cardiologist should be used for assessment of eligibility whenever possible.
- •Allergies and Adverse Drug Reaction Has had prior use of BMS-986020 or has known hypersensitivity to any of the components of study treatment.
- •Other Exclusion Criteria
- •Is not a suitable candidate for enrollment or is unlikely to comply with the requirements of this study, in the opinion of the investigator.
- •Has smoked cigarettes within 4 weeks or screening or is unwilling to avoid tobacco products throughout the study.
- •Is expected to receive a lung transplant within 1 year from randomization or, for subjects at sites in the United States, is on a lung-transplant waiting list at screening.
- •Prisoners or subjects who are involuntarily incarcerated.
- •Subjects who are compulsorily detained for treatment either of a psychiatric or physical (e.g., infectious disease) illness.
- •Inability to comply with restrictions and prohibited activities/treatments as listed in Section 3.3 of the Protocol.
研究组 & 干预措施
Arm 1: BMS 986020, 600 mg. once daily
Experimental
BMS-986020, 600 mg tablets, by mouth, once daily, 26 weeks
干预措施: BMS-986020 (Drug)
Arm 2: BMS-986020, 600 mg twice daily
Experimental
BMS-986020, 600 mg tablets, by mouth, twice daily, 26 weeks
干预措施: BMS-986020 (Drug)
Arm 3: Placebo matching with BMS-986020
Placebo Comparator
Placebo, 0 mg tablets, by mouth, twice daily, 26 weeks
干预措施: Placebo matching with BMS-986020 (Drug)
结局指标
主要结局
Change From Baseline in Forced Vital Capacity (FVC) Rate to Week 26
时间窗: Baseline, Week 26
FVC is the is the total amount of air exhaled during the forced expiratory volume test that is measured during spirometry; and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which is used to dilate participant's bronchial (breathing) tubes.
次要结局
- Geometric Mean Ratio (GMR) of Quantitative Lung Fibrosis (QLF) Score at Week 26 to Baseline(Baseline, Week 26)
- Number of Participants With Death or Respiratory Hospitalization or 10 Percent (%) Decline in Absolute Volume of FVC or 25-Meter Loss in 6-Minute Walk Distance (6MWD)(Upto Day 210)
- Mean Change From Baseline in Six-minute Walk Test (6MWT) Distance to Week 26(Baseline, Week 26)
- Number of Participants With Death or Non-Elective Hospitalization(Upto Day 210)
- Number of Participants With Definite or Probable Acute Exacerbation (AEx) of Idiopathic Pulmonary Fibrosis (IPF)(Upto Day 210)
- Maximum Observed Plasma Concentration (Cmax) BMS-986020(Day 1 and Day 7)
- Area Under the Plasma Concentration-time Curve Over 12 Hours Post-dose AUC(0-12) of BMS -986020(Day 1 and Day 7)
- Mean Change From Baseline in the University of California at San Diego Shortness of Breath Questionnaire (UCSD SOBQ) Total Score as a Measure of Dyspnea to Week 26(Baseline, Week 26)
- Mean Change From Baseline in Forced Vital Capacity (FVC) to Week 26(Baseline, Week 26)
- Accumulation Index (AI) of BMS-986020(Day 7)
- Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36) to Week 26(Baseline, Week 26)
- Mean Change From Baseline in Carbon Monoxide Diffusing Capacity (DLCO) to Week 26(Baseline, Week 26)
- Time of Maximum Observed Plasma Concentration (Tmax) of BMS-986020(Day 1 and Day 7)
- Area Under the Concentration Time Curve in One Dosing Interval of BMS -986020 in at Steady-state(Day 1 and Day 7)
- Apparent Oral Clearance (CLF/F) of BMS -986020(Day 1 and Day 7)
- Average Concentration of BMS -986020 at Steady State (Css[Avg])(Day 7)
研究者
研究点 (53)
Loading locations...
相似试验
已完成
2 期
A Safety and Efficacy Study in Subjects With Diabetic Neuropathic PainDiabetic Neuropathic PainNCT00548925AbbVie (prior sponsor, Abbott)124
终止
1 期
A Study of LY3006072 in Healthy ParticipantsHealthy VolunteersNCT01640249Eli Lilly and Company18
招募中
1 期
Study of Lunresertib Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid TumorsAdvanced Solid TumorNCT04855656Debiopharm International SA464
已完成
2 期
Comparison Of 6 CP-690,550 Doses Vs.Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid ArthritisArthritis, RheumatoidNCT00413660Pfizer509
已完成
2 期
A Dose-finding Study to Evaluate the Change in Weight After Treatment With LIK066 in Japanese Patients With ObesityObesityNCT03320941Novartis Pharmaceuticals126