Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of the Efficacy and Safety of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis (ASCEND Trial)
Brief Summary: PIPF-016 (ASCEND) is a Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of the Efficacy and Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. The study objectives are to confirm the treatment effect of pirfenidone compared with placebo on change in percent predicted forced vital capacity (%FVC) in patients with idiopathic pulmonary fibrosis (IPF), and to confirm the safety of treatment with pirfenidone compared with placebo in patients with IPF.


Options:
A: Inclusion Criteria:

* The presence of either limited (cutaneous thickening distal but not proximal to elbows and knees, with or without facial involvement) or diffuse (cutaneous thickening proximal to elbows and knees, often involving the chest or abdomen) scleroderma, as determined by American College of Rheumatology criteria
* Dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index)
* FVC less than or equal to 80 percent of predicted value at screening and less than or equal to 85 percent predicted at baseline
* Onset of the first non-Raynaud manifestation of SSc within the prior 84 months
* Presence of any ground glass opacification on thoracic high resolution computerized tomography (HRCT)
* Repeat FVC at the baseline visit (Visit 2) within 10 percent of the FVC measured at screening and less than or equal to 85 percent predicted.

Exclusion Criteria:

* FVC less than 45 percent of predicted value at either screening or baseline
* Carbon monoxide diffusing capacity (DLCO) (HBg-corrected) less than 30 percent of predicted value and less than 40 percent of predicted when documentation of pulmonary artery pressures by echocardiogram, right heart catheterization or magnetic resonance imaging identifies clinically significant pulmonary hypertension. All participants with a DLCO less than 40 percent predicted must have documentation of pulmonary artery pressures in order to be considered for inclusion.
* FEV1/FVC ratio less than 65 percent at either screening or baseline
* Clinically significant abnormalities on HRCT not attributable to scleroderma
* Diagnosis of clinically significant resting pulmonary hypertension requiring treatment, as ascertained before study evaluation or as part of a standard of care clinical assessment performed outside of the study protocol
* Persistent unexplained hematuria (more than 10 red blood cells per high-power field \[RBCs/hpf\])
* History of persistent leukopenia (white blood cell count less than 4000) or thrombocytopenia (platelet count less than 150,000)
* Clinically significant anemia (less than 10g/dl)
* Baseline liver function test (LFTs) or bilirubin more than 1.5 times the upper limit of normal, other than that due to Gilbert's disease
* Concomitant and present use of captopril
* Serum creatinine more than 2.0mg/dL
* Uncontrolled congestive heart failure
* Pregnancy (documented by urine pregnancy test) and/or breast feeding
* Prior use of oral CYC or MMF for more than 8 weeks or the receipt of more than two intravenous doses of CYC in the past
* Use of CYC and/or MMF in the 30 days before random assignment
* Active infection (lung or elsewhere) whose management would be compromised by CYC or MMF
* Other serious concomitant medical illness (e.g., cancer), chronic debilitating illness (other than scleroderma), or unreliability or drug abuse that might compromise the patient's participation in the study
* Current use, or use within the 30 days prior to random assignment, of prednisone (or equivalent) in doses of more than 10 mg/day
* If of child bearing potential (a female participant \<55 years of age who has not been postmenopausal for \> 5 years and who has not had a hysterectomy and/or oophorectomy), failure to employ two reliable means of contraception (which may include surgical sterilization, barrier methods, spermicidals, intrauterine devices, and/or hormonal contraception).
* Use of contraindicated medications; more information on this criterion can be found in the study protocol
* Smoking of cigars, pipes, or cigarettes in the 6 months before study entry
* Use of medications with putative disease-modifying properties within the past month (e.g., D-penicillamine, azathioprine, methotrexate, Potaba)
B: Primary Inclusion criteria:

* diagnosis of idiopathic pulmonary fibrosis
* 40 to 80 years of age
* Forced Vital Capacity greater than or equal to 50% predicted value
* Carbon monoxide diffusing capacity greater than or equal to 35% predicted value
* either Forced Vital Capacity or Carbon monoxide diffusing capacity less than or equal to 90% predicted value
* no improvement in past year
* able to walk 150 meters in 6 minutes and maintain saturation greater than or equal to 83% while on no more than 6 liters per minute (L/min) supplemental oxygen

Primary Exclusion criteria:

* unable to undergo pulmonary function testing
* evidence of significant obstructive lung disease or airway hyper-responsiveness
* in opinion of investigator patient is expected to need and be eligible for a lung transplant within 72 weeks after randomization
* active infection
* liver disease
* cancer or other medical condition likely to result in death within 2 years
* diabetes
* pregnancy or lactation
* substance abuse
* personal or family history of long QT (Q wave,T wave) syndrome
* other IPF treatment
* unable to take study medication
* withdrawal from other IPF trials
C: Select Inclusion Criteria:

1. Diagnosis of idiopathic pulmonary fibrosis (IPF), consistent with the ATS 2011 Guidelines, of 6-48 months' duration
2. Age 40 to 80 at randomization
3. Percent Forced Vital Capacity (%FVC) ≥50% and ≤90% at screening
4. Percent Carbon Monoxide Diffusing Capacity (%DLCO) ≥30% and ≤90% at screening

Select Exclusion Criteria:

1. Forced expiratory volume in one second (FEV1)/FVC ratio \<0.8 after administration of bronchodilator at Screening
2. Expected to receive a lung transplant within 1 year from randomization or, for patients at sites in the United States, on a lung transplant waiting list at randomization
3. Known explanation for interstitial lung disease
4. History of asthma or chronic obstructive pulmonary disease
5. Active infection
6. Ongoing IPF treatments including investigational therapy, immunosuppressants, and cytokine modulating agents
7. History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months
D: Inclusion Criteria:

* Forced vital capacity (FVC) greater than or equal to 50% of predicted value
* Diffusion capacity (DLCO) greater than or equal to 30% of predicted value
* Diagnosis of IPF by modified American Thoracic Society (ATS) criteria in the 48 months before study entry

Exclusion Criteria:

* History of clinically significant environmental exposure known to cause pulmonary fibrosis
* Diagnosis of connective tissue disease as the likely cause of the interstitial disease
* Extent of emphysema greater than the extent of fibrotic change (i.e., honeycombing, reticular changes) on high resolution computed tomography (HRCT) scan
* Forced expiratory volume in 1 second (FEV1)/FVC ratio less than 0.65 at the time of screening (post-bronchodilator)
* Partial pressure of arterial oxygen (PaO2) less than 55 mm Hg (less than 50 mm Hg at Denver study site)
* Residual volume greater than 120% predicted at the time of screening (post-bronchodilator)
* Evidence of active infection
* Significant bronchodilator response on screening spirometry, defined as change in FEV1 greater than or equal to 12% and absolute change greater than 200 mL OR change in FVC greater than or equal to 12% and absolute change greater than 200 mL
* Screening and baseline FVC measurements (in liters, post-bronchodilator) differing by 11%
* Listed for lung transplantation
* History of unstable or deteriorating cardiac disease
* Heart attack, coronary artery bypass, or angioplasty in the 6 months before study entry
* Unstable angina pectoris or congestive heart failure requiring hospitalization in the 6 months before study entry
* Uncontrolled arrhythmia
* Severe uncontrolled high blood pressure
* Known HIV or hepatitis C
* Known cirrhosis and chronic active hepatitis
* Active substance and/or alcohol abuse
* Pregnant or breastfeeding
* Women of childbearing potential who are not using a medically approved means of contraception
* Any clinically relevant lab abnormalities, including the following:

  1. Creatinine greater than twice the upper limit of normal (ULN)
  2. Hematology outside of specified limits

     1. White blood cells less than 3,500/mm3
     2. Hematocrit less than 25% or greater than 59%
     3. Platelets less than 100,000 mm3 at the time of screening
  3. Any of the following liver function test criteria above specified limits

     1. Total bilirubin greater than twice the ULN
     2. Aspartate (AST) or alanine aminotransferases (ALT) greater than 1.5 the ULN
     3. Alkaline phosphatase greater than three times the ULN
     4. Albumin less than 3.0 mg/dL at the time of screening
* Known hypersensitivity to study medication
* Any condition other than IPF that, in the opinion of the site PI, is likely to result in death in the 1 year after study entry
* Any condition that, in the judgment of the PI, might cause participation in this study to be detrimental or makes the person a poor candidate for the study

Answer: C