NCT02951429已完成2 期
A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Sildenafil Added to Pirfenidone in Patients With Advanced Idiopathic Pulmonary Fibrosis and Intermediate or High Probability of Group 3 Pulmonary Hypertension
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
- 177
- 试验地点
- 56
- 主要终点
- Percentage of Participants With Disease Progression, as Determined by Relevant Decline in 6 Minute Walk Distance (6MWD) of At Least (>=) 15 Percent (%) From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause
研究概览
简要总结
This Phase IIb, randomized, placebo-controlled, multicenter, international study will evaluate the efficacy, safety, and tolerability of sildenafil or placebo added to pirfenidone (Esbriet) treatment in participants with advanced IPF and intermediate or high probability of Group 3 pulmonary hypertension (PH) who are on a stable dose of pirfenidone with demonstrated tolerability. Participants will be randomized to receive 1 year of treatment with either oral sildenafil or matching placebo while continuing to take pirfenidone.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of IPF for at least 3 months prior to Screening
- •Confirmation of IPF diagnosis by the investigator in accordance with the 2011 international consensus guidelines at screening
- •Advanced IPF (defined as a measurable carbon monoxide diffusing capacity [DLCO] less than or equal to (<=)40% of predicted value at Screening) and intermediate or high probability of group 3 pulmonary hypertension (PH)
- •Participants receiving pirfenidone for at least 12 weeks, at a dose in the range of 1602 to 2403 mg/day for at least 4 weeks prior to Screening and must not have experienced either a new or ongoing adverse event of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 4.03) Grade 2 or higher and considered by the investigator to be related to pirfenidone, or an interruption of pirfenidone treatment of greater than (>)7 days for any reason
- •WHO Functional Class II or III at Screening
- •6MWD of 100 to 450 meters at screening
- •Women of childbearing potential and for men who are not surgically sterile agreement to remain abstinent or use of contraceptive measures
排除标准
- •History of any of the following types of PH: Group 1 (PAH); Group 1 (pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis); Group 2 (left-heart disease); Group 3 (due to conditions other than interstitial lung disease, including chronic obstructive pulmonary disease [COPD], sleep-disordered breathing, alveolar hypoventilation, high altitude, or developmental abnormalities); Group 4 (chronic thromboembolic pulmonary hypertension); Group 5 (other disorders)
- •History of clinically significant cardiac disease
- •History of coexistent and clinically significant COPD, bronchiectasis, asthma, inadequately treated sleep-disordered breathing, or any clinically significant pulmonary diseases or disorders other than IPF or PH secondary to IPF
- •History of use of drugs and toxins known to cause PAH, including aminorex, fenfluramine, dexenfluramine, and amphetamines
- •FEV1/FVC ratio less than (<) 0.70 post bronchodilator; SpO2 saturation at rest <92% with >= 6 liters (L) of supplemental oxygen at Screening
- •Extent of emphysema greater than the extent of fibrotic changes (honeycombing and reticular changes) on any previous high-resolution computed tomography (HRCT) scan, in the opinion of the Investigator
- •Smoked tobacco within 3 months prior to screening or is unwilling to avoid tobacco products (cigarettes, pipe, cigars) throughout the study
- •Illicit drug or significant alcohol abuse
- •Electrocardiogram (ECG) with a heart-rate corrected QT interval (corrected using Fridericia's formula [QTcF]) >=500 milliseconds (ms) at screening, or a family or personal history of long QT syndrome
- •Exclusion criteria based on pirfenidone reference safety information:
- •participants with a history of angioedema due to pirfenidone;
- •concomitant use of fluvoxamine
- •Exclusion criteria based on sildenafil reference safety information:
- •co-administration with nitric oxide donors or organic nitrates, phosphodiesterase-5 (PDE5) inhibitors, guanylate cyclase stimulators, and most potent of the Cytochrome P450 3A4 (CYP3A4) inhibitors;
- •loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION);
- •use of an alpha-blocker;
- •participants with bleeding disorders or active peptic ulceration;
- •known hereditary degenerative retinal disorders such as retinitis pigmentosa;
- •galactose intolerance
研究组 & 干预措施
Pirfenidone + Placebo
Placebo Comparator
Participants will receive pirfenidone along with placebo matched to sildenafil, orally, three times a day (TID) for 52 weeks.
干预措施: Pirfenidone (Drug)
Pirfenidone + Placebo
Placebo Comparator
Participants will receive pirfenidone along with placebo matched to sildenafil, orally, three times a day (TID) for 52 weeks.
干预措施: Placebo (Drug)
Pirfenidone + Sildenafil
Experimental
Participants will receive pirfenidone along with sildenafil, orally, TID for 52 weeks.
干预措施: Pirfenidone (Drug)
Pirfenidone + Sildenafil
Experimental
Participants will receive pirfenidone along with sildenafil, orally, TID for 52 weeks.
干预措施: Sildenafil (Drug)
结局指标
主要结局
Percentage of Participants With Disease Progression, as Determined by Relevant Decline in 6 Minute Walk Distance (6MWD) of At Least (>=) 15 Percent (%) From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause
时间窗: Baseline up to Week 52
Disease Progression defined as relative decline in 6-minute walking distance (6MWD) from baseline (defined as \>25% from baseline or 15-25% from baseline associated with worsening oxygen saturation, worsening Borg score, or increased oxygen requirements), respiratory-related non-elective hospitalizations, or all-cause mortality.
次要结局
- St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52(Baseline, Week 52)
- University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Changes From Baseline at Week 52(Baseline, Week 52)
- Change From Baseline in Distance Walked, 6-minute Walking Distance (6MWD) Test at Week 52(Baseline up to Week 52)
- Change From Baseline in Oxygen Requirements, 6-minute Walking Distance (6MWD) Test at Week 52(Baseline up to Week 52)
- Change From Baseline in Other 6-minute Walking Distance (6MWD) Parameters at Week 52(Baseline up to Week 52)
- Percentage of Participants With Adverse Events(Baseline up to Week 52 + 28 days)
- Time to Multiple Occurrence of Disease Progression Events(Baseline up to Week 52)
- Percentage of Participants With Decline From Baseline in 6-minute Walking Distance (6MWD) of >= 15%(Baseline up to Week 52)
- Time to First Occurrence of Relevant ≥15% Decline From Baseline in 6-minute Walking Distance (6MWD)(Baseline up to Week 52)
- Time to Respiratory-Related Non-Elective Hospitalization From Baseline to Week 52(Baseline up to Week 52)
- Time to All-Cause Non-Elective Hospitalization(Baseline up to Week 52)
- Time to Death From Any Cause(Baseline up to Week 52)
- Percentage of Participants With Lung Transplantation(Baseline up to Week 52)
- Time to Respiratory-Related Death(Baseline up to Week 52)
- Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Peak Tricuspid Regurgitation Velocity(Baseline, Week 52)
- Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Pulmonary Artery Pressure (PAPs)(Baseline, Week 52)
- Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Tricuspid Annular Plane Systolic Excursion (TAPSE)(Baseline, Week 52)
- Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Left Ventricular Ejection Fraction (LVEF)(Baseline, Week 52)
- Change From Baseline to Week 52 in Carbon Monoxide Diffusing Capacity/ Pulmonary Diffusing Capacity (DLCO)(Baseline, Week 52)
- Change From Baseline to Week 52 in Forced Vital Capacity (FVC)(Baseline, Week 52)
- Time to First Occurrence of Disease Progression(Baseline up to Week 52)
- Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Right Ventricle Basal Diameter(Baseline, Week 52)
- Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52(Week 52)
- Change From Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Level (pg/mL) at Week 52(Baseline, Week 52)
- Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Inferior Vena Cava Diameter(Baseline, Week 52)
- Borg Scale Result at the End of the Test at Week 52(Week 52)
研究者
研究点 (56)
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