a new era in ipf: trials and treatments craig thurm, md director, pulmonary medicine director,...

A NEW ERA in IPF:Trials and Treatments

Craig Thurm, MDDirector, Pulmonary Medicine

Director, Pulmonary FellowshipMedical Director, Respiratory CareJamaica Hospital Medical Center

Disclosure of Relevant Financial RelationshipsIt is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty, activity planners, content reviewers, and staff participating in this activity will disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this educational activity. The intent of this disclosure is not to prevent a person with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has identified and resolved any and all conflicts of interest prior to the release of this activity.

Faculty DisclosuresCraig Thurm, MD has received research and grant support from Boehringer Ingelheim, Bristol-Myers Squibb, Cubist, and Forest Pharmaceuticals. He has served as a consultant for Meda Pharmaceuticals and Sunovion Pharmaceuticals, and is a shareholder with Teva Pharmaceuticals. He has received honoraria from Boehringer Ingelheim, CSL Behring, Forest Pharmaceuticals, GlaxoSmithKlein, InterMune, Janssen Pharmaceuticals, and Merck.

Activity Staff DisclosuresThe planners, reviewers, editors, staff, or other members at The France Foundation who control content have no relevant financial relationships to disclose.

Educational SupportSupported by educational grants from Boehringer Ingelheim and InterMune.

Accreditation / Designation Statements

The France Foundation is accredited with commendation by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The France Foundation designates this activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

How to Receive CME Credit

• Complete the pretest (page one of your handout) and give this page to the coordinator when you leave

• Keep page two of your handout and follow the instructions to go online to claim CME credit

• Your CME certificate will be available to download

Educational Activity Learning Objective

Upon completion of this course, the participants should be able to:• Explain the considerations associated with clinical evaluation,

imaging, and surgical biopsy in differentially diagnosing IPF• Identify opportunities for interdisciplinary collaboration and

consultation and key aspects of guideline recommendations that can facilitate early and accurate IPF diagnosis

• Summarize the current understanding of the IPF disease process and strategies that can help measure disease progression and treatment response

• Evaluate clinical trial data on available and emerging treatments for IPF

• Identify opportunities for referral as part of multidisciplinary IPF management plan

Outline

• Diagnosis• Pathophysiology model• IPF drug trials

–PANTHER (NAC)–ASCEND (pirfenidone)– INPULSIS (nintedanib)

• Recent drug approvals!• Referral of patients with IPF

Idiopathic Pulmonary Fibrosis

• Peripheral lobular fibrosis of unknown cause

• Clinical impact– Exertional dyspnea

– Cough

– Functional and exercise limitation

– Impaired quality-of-life

– Risk for acute respiratory failure and death

• Median survival time of 3-5 years

• Two new drugs approved by the FDA in October 2014‒ Nintedanib (Ofev)

‒ Pirfenidone (Esbriet)

Diffuse Parenchymal Lung Disease (DPLD)

DPLD of known cause, eg, drugs or association, eg, collagen vascular disease

Idiopathic interstitial

pneumonias

Granulomatous DPLD, eg,

sarcoidosis

Other forms of DPLD, eg, LAM,

HX, etc

Idiopathic pulmonary

fibrosis

IIP other than idiopathic

pulmonary fibrosis

Desquamative interstitial pneumonia

Acute interstitial pneumonia

Nonspecific interstitial pneumonia (provisional)

Respiratory bronchiolitis interstitial lung disease

Cryptogenic organizing pneumonia

Lymphocytic interstitial pneumonia

ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002;165:277-304.

Major Idiopathic Interstitial Pneumonias

Category Clinical-Radiologic-Pathologic Diagnosis

Associated Radiographic and/or Pathologic pattern

Chronic fibrosing

IPF UIP

Idiopathic nonspecific interstitial Pneumonia (iNSIP) NSIP

Smoking-related

Respiratory bronchiolitis-ILD (RB-ILD) Respiratory bronchiolitis

Desquamative interstitial pneumonia (DIP) Desquamative interstitial pneumonia

Acute/ subacute

Cryptogenic organizing pneumonia (COP) Organizing pneumonia

Acute interstitial pneumonia (AIP) Diffuse alveolar damage

Travis et al. Am J Respir Crit Care Med. 2013;188:733-748.

Diagnostic Algorithm for IPF

Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.

Suspected IPF

Identifiable causes for ILD?

HRCT

Surgical Lung Biopsy

MDD

IPF/Not IPFIPF Not IPF

No

Possible UIPInconsistent w/ UIP

UIPProbable UIPNon-classifiable fibrosis

Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.

2011 ATS/ERS Diagnostic Criteria for IPF

*also known as diffuse parenchymal lung disease, DPLD

Exclusion of known causes of ILD*

UIP pattern on HRCT without surgical biopsy

ORDefinite/possible UIP pattern on HRCT with a surgical lung

biopsy showing definite/probable UIP

AND


Normal Lungs Usual Interstitial Pneumonia


Normal Lung Usual Interstitial Pneumonia


Normal Lung Fibroblastic Focus inUsual Interstitial Pneumonia

Clinical-Radiologic-Pathologic Approach to ILD

Specific diagnosis

Clinical picture

Radiologic pattern (HRCT)Pathologic pattern

(lung biopsy)

DrugsInfections-viruses

RadiationOther diseases

Steele MP, Schwartz DA. Annu Rev Med. 2013;64:265-276.

Exogenous and Endogenous stimuli

Microscopic lung injury:Separated spatially and temporally

Lung homeostasis Interstitial lung disease

Dust Fumes

Cigarette smokeAutoimmune conditions

Genetic predisposition

Wound healingIntact Aberrant

ILD Disease Progression

Eras of Care for IPF

ATS Statement2011

Pre-ATS Statement 2011 2011-2013 2014

Trial N Primary Endpoint ResultInterferon-beta (1999) 167 Progression-free survival time Negative

Interferon-gamma (GIPF-001) 330 Progression-free survival Negative

Interferon-gamma (Inspire) 826 Survival time Negative

Pirfenidone (CAPACITY 1) 344 Change in FVC Negative

Pirfenidone (CAPACITY 2) 435 Change in FVC Positive

Pirfenidone (Ogura) 275 Change in FVC Positive

Etanercept 100 Change in DLco, FVC Negative

Imatinib Mesylate 120 Progression-free survival Negative

Bosentan (BUILD 1 and 2) 132 Change in 6MW Negative

Bosentan (BUILD 3) 390 Progression-free survival time Negative

Anticoagulation 56 Survival Positive

N-acetylcysteine (NAC) (IFIGENIA) 184 Change in FVC, DLco Positive

Sildenafil (STEP) 29 Change in 6MWD, Borg dyspnea index Negative

Completed Trials for IPF: Prior to 2011 Consensus Statement

Noth I, et al. Am J Respir Crit Care Med. 2012 Jul 1;186(1):88-95.\

Subsequent trials showed that warfarin and NAC/azathioprine/prednisone

should not be used for IPF

2011 Guidelines on Management of IPFTreatment Strong

ForWeak

ForWeak

AgainstStrong Against

Corticosteroid XColchicine XCyclosporine A XInterferon γ 1b XBosentan XEtanercept XNAC/Azathioprine/Prednisone XNAC XAnticoagulation XPirfenidone XMechanical ventilation XPulmonary rehab XLong-term oxygen XLung transplantation X

Three Recent IPF Clinical Trials American Thoracic Society 2014

• PANTHER N-acetylcysteine (NAC)• ASCEND pirfenidone• INPULSIS nintedanib (BIBF1120)

PANTHERN-acetylcysteine (NAC)

NAC Does Not Reduce FVC Decline

Martinez FJ, et al. N Engl J Med. 2014;370(22):2093-2101.

Conclusion: NAC offered no significant benefit with respect to the preservation of FVC in patients with IPF with mild-to-moderate impairment in lung function

ASCENDPirfenidone

Possible Mechanisms of Pirfenidone Action

Hilberg O, et al. Clin Respir J. 2012;6:131-143.

TNF-αIL-6

Pirfenidone

TGF-βIL-6

MMPsCollagenases

ROIs

Collagen

• Antifibrotic• Molecular target

unclear• Active in several

animal models of fibrosis (lung, liver, kidney)

Noble P, et al. Lancet. 2011;377:1760-1769.

CAPACITY 2011

CAPACITY-2 CAPACITY-1

• One pirfenidone trial was positive, one was negative• CAPACITY-1 placebo group FVC declined more slowly than expected

ATS 2011

2011-2013 2014Pre-2011

CAPACITY Endpoints

Endpoint CAPACITY-2 CAPACITY-1FVC X

Overall survival X X

Progression-free survival X

Six-minute walk distance X DLCO X X

Dyspnea X X

Exertional desaturation X X

Noble P, et al. Lancet. 2011;377:1760-1769.

ASCEND 2014ATS

20112011-2013Pre-2011 2014

Endpoints

10: Δ FVC or death

20: 6-MWDPFSDyspneaDeath

ASCEND Study Design

King TE, et al. N Engl J Med. 2014;370(22):2083-2092.

Oral Pirfenidone 2403 mg Daily

Placebo

52 Weeks

PFS - Progression-free survival

Inclusion Criteria

• Age 40-80• Confirmed IPF• 50 - 90% FVC pred • 30 - 90% DLCO pred • FEV1/FVC ≥ 0.80 • 6-MWD ≥ 150 m

555 Patients

Primary ASCEND Endpoint Achieved


Patie

nts

with

≥ 1

0% F

VC

Dec

line

or D

eath

(%)

Week

Primary Endpoint

48% RelativeReduction

Pirfenidone Increased Progression-Free Survival*


*Progression is first occurrence of death, 10% ↓ FVC, or 50 m ↓ 6MWD

Pirfenidone Reduces Loss of FVC

<0.000001King TE, et al. N Engl J Med. 2014;370(22):2083-2092.

235 ml

428 ml

Rank ANCOVA P-value < 0.00001 at each indicated time point

Mea

n Ch

ange

(ml)

Week

More Pirfenidone Patients Maintain Walk Distance or Survive


Prop

ortio

n of

Pati

ents

with

≥5

0 m

Dec

line

or D

eath

(%)

Week


ASCEND Adverse Events Adverse Event Pirfenidone (%)

(N = 278)Placebo (%)

(N = 277)Δ (%)

Nausea 36 13.4 22.6 Rash 28.1 8.7 19.4 Dyspepsia 17.6 6.1 11.5 Anorexia 15.8 6.5 9.3 GERD 11.9 6.5 5.4 Weight Loss 12.6 7.9 4.7 Insomnia 11.2 6.5 4.7 Dizziness 17.6 13 4.6 Vomiting 12.9 8.7 4.2

… … … …

Dyspnea 14.7 17.7 -3 Cough 25.2 29.6 -4.4 IPF 9.4 18.1 -8.7


Pirfenidone Associated with Less MortalityASCEND and CAPACITY data

From randomization to 28 days after last doseCox proportional hazard modelLog-rank test


ASCEND Summary

• Treatment with pirfenidone for 52 weeks significantly reduced disease progression, as measured by – Changes in % predicted FVC (P < 0.001)

– Changes in 6-minute walk distance (P = 0.04)

– Progression-free survival (P < 0.001)

• Treatment with pirfenidone reduced all-cause mortality and treatment emergent IPF-related mortality in pooled analyses at week 52

• Pirfenidone was generally safe and well tolerated

37

• Pirfenidone, as compared with placebo, reduced disease progression in patients with IPF

• Treatment was generally safe, had an acceptable side effect profile, and was associated with fewer deaths

ASCEND Conclusions

38

• Approved October 15, 2014• Indicated for the treatment of IPF• Dosage and administration

– 801 mg (three 267 mg capsules) three times daily with food – Doses should be taken at the same time each day– Initiate with titration

• Days 1 through 7: 1 capsule 3x per day• Days 8 through 14: 2 capsules 3x per day• Days 15 onward: 3 capsules 3x per day

–Consider temporary dosage reduction, treatment interruption, or discontinuation for management of adverse reactions.

• Prior to treatment, conduct liver function tests.

FDA Approval of Pirfenidone (Esbriet)

http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails/. Accessed October 2014.


Pirfenidone Warnings and PrecautionsTemporary dosage reductions or discontinuations may be required

• Elevated liver enzymes: ALT, AST, and bilirubin elevations have occurred with pirfenidone. Monitor ALT, AST, and bilirubin before and during treatment.

• Photosensitivity and rash: Photosensitivity and rash have been noted with pirfenidone. Avoid exposure to sunlight and sunlamps. Wear sunscreen and protective clothing daily.

• Gastrointestinal disorders: Nausea, vomiting, diarrhea, dyspepsia, gastro-esophageal reflux disease, and abdominal pain have occurred with pirfenidone.


Pirfenidone: Other Considerations• Post-marketing experience (reactions of unknown frequency)

– Agranulocytosis – Angioedema – Bilirubin increased in combination with increases of ALT and AST

• Drug interactions– Metabolized primarily via CYP1A2– Activators and inhibitors of CYP1A2 should be used with caution with

pirfenidone

• Use with caution with mild/moderate hepatic impairment, not recommended for patients with severe impairment

• Use with caution with mild/moderate/severe renal impairment, not recommended for patients with ESRD requiring dialysis

• Smoking causes decreased exposure to pirfenidone. Instruct patients to stop smoking prior to treatment with pirfenidone and to avoid smoking when using pirfenidone.

INPULSISNintedanib

Possible Mechanisms of Nintedanib Action

• Triple kinase inhibitor• Phosphatase activator• Antiangiogenic,

antitumor activity VEGF

Nintedanib

PDGF FGF SHP-1

Hilberg F, et al. Cancer Res. 2008;68(12):4774-4782.Tai WT, et al. J Hepatol. 2014;61(1):89-97.

Pleiotropic Effects

Richeldi L, et al. N Engl J Med.2011:365;1079-1089.

Nintedanib Showed Promise for FVC Endpoint

ATS 2011

2011-2013 2014Pre-2011

INPULSIS 2014ATS

20112011-2013Pre-2011 2014

Richeldi L, et al. N Engl J Med. 2014;370(22):2071-2082.

INPULSIS-1 and INPULSIS-2 Study Design

Endpoints

10: ΔFVC

20: Time to first AE Δ SGRQ

Inclusion Criteria

• Age > 40• IPF ≤ 5y• ≥ 50% FVC pred • 30 - 79% DLCO pred • HRCT within 1y

Nintedanib 300 mg Daily

Placebo

52 Weeks

3

2

1066 Patients

AE – Acute ExacerbationSGRQ – St. George’s Respiratory Questionnaire


Primary INPULSIS Endpoint AchievedAnnual Rate of Change of FVC

INPULSIS-1 INPULSIS-2



Nintedanib Placebo

Nintedanib Reduces Loss of FVC

INPULSIS-1

INPULSIS-2

Mea

n O

bser

ved

Chan

ge fr

om B

asel

ine

in F

VC (m

L)

Richeldi L, et al. N Engl J Med. 2014;370(22):2071-2082. Week

Mixed Findings for Time to First Acute Exacerbation

Cum

ulati

ve In

cide

nce

of F

irst A

cute

Exa

cerb

ation

(%)

INPULSIS-1

INPULSIS-2

Richeldi L, et al. N Engl J Med. 2014;370(22):2071-2082. Days


Common Nintedanib Adverse Events

Event

INPULSIS-1 INPULSIS-2

Nintedanib (n = 309)

Placebo (n = 204)

Nintedanib (n = 329)

Placebo (n = 219)

Any (%) 96 89 94 90Diarrhea (%) 62 19 63 18

Nausea(%) 23 6 26 7


INPULSIS Summary

• Nintedanib had significant benefit in adjusted annual rate of change in FVC • INPULSIS-1 Δ = 125.3 ml P < 0.001• INPULSIS-2 Δ = 93.7 ml P < 0.001

• Nintedanib had significant benefit in time to the first acute exacerbation in INPULSIS-2• INPULSIS-1 HR = 1.15 P = 0.67• INPULSIS-2 HR = 0.38 P = 0.005

• Significant difference in favor of nintedanib for the change from baseline in the total SGRQ score in INPULSIS-2 but not INPULSIS-1


INPULSIS Conclusions

• Nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression

• Nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients

52

• Approved October 15, 2014• Indicated for the treatment of IPF• Dosage and administration

–150 mg twice daily approximately 12 hours apart taken with food

–Consider temporary dose reduction to 100 mg, temporary interruption, or discontinuation for management of adverse reactions.

–Prior to treatment, conduct liver function tests.

FDA Approval of Nintedanib (Ofev)


53

• Elevated liver enzymes: ALT, AST, and bilirubin elevations have occurred with nintedanib. Monitor ALT, AST, and bilirubin before and during treatment. Temporary dosage reductions or discontinuations may be required.

• GI disorders: Diarrhea, nausea, and vomiting have occurred with nintedanib. Treat patients at first signs with adequate hydration and antidiarrheal medicine (e.g., loperamide) or anti-emetics. Discontinue nintedanib if severe diarrhea, nausea, or vomiting persists despite symptomatic treatment.

• Embryofetal toxicity: Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant.

• Arterial thromboembolic events have been reported. Use caution when treating patients at higher cardiovascular risk including known CAD.

• Bleeding events have been reported. Use nintedanib in patients with known bleeding risk only if anticipated benefit outweighs the potential risk.

• GI perforation has been reported. Use nintedanib with caution when treating patients with recent abdominal surgery. Discontinue nintedanib in patients who develop GI perforation. Only use nintedanib in patients with known risk of GI perforation if the anticipated benefit outweighs the potential risk.

Nintedanib Warnings and Precautions


54

Nintedanib: Other Considerations

• Drug interactions– Nintedanib is a substrate of P-glycoprotein (P-gp) and CYP3A4– Concomitant use of P-gp and CYP3A4 inducers with nintedanib should be

avoided– Patients treated with P-gp and CYP3A4 inhibitors and nintedanib should

be monitored closely for adverse reactions

• Nintedanib is a VEGFR inhibitor, and may increase the risk of bleeding. Monitor patients on full anticoagulation therapy closely for bleeding and adjust anticoagulation treatment as necessary.

• Nintedanib not recommended for patients with moderate or severe hepatic impairment

• < 1% excreted via the kidney; no data on patients with severe renal impairment and ESRD


Current Phase 2 Trials for IPFNext Generation Therapy?

Trial Target N Primary Endpoint

Co-trimoxazole (Ph 3) Pneumocystis jiroveci 56 Change in FVC or respir. Hospital’n

FG-3019 Anti-CTGF 90 Change in FVC from baseline

Rituximab CD-20 58 Titers of anti-HEp-2 autoantibodies

Simtuzumab Anti-LOXL2 500 PFS

GC-1008 TGF- 25 Safety, tolerability, PK

QAX576 Anti-IL-13 40 Safety, tolerability, FVC

Tralokinumab Anti-IL-13 302 Change in FVC from baseline

STX-100 αvβ6 32 Adverse events

BMS-986020 LPA Receptor 300 Rate of change in FVC

Clinical Trial Conclusions

• 2014 is a watershed year in IPF– NAC did not show efficacy (PANTHER)– Pirfenidone (ASCEND) and nintedanib (INPULSIS) showed

efficacy in mild/moderate IPF– Pirfenidone and nintedanib approved 10/15/14 for the

treatment of IPF– Still need data on advanced disease, combination therapy,

long-term safety, adherence

• Implications of having approved drug(s)– Need early and accurate diagnosis– Role of IPF and ILD Centers of Excellence is evolving

EARLY REFERRAL for SPECIALTY CARE

Why refer early to an ILD Center?

• Diagnostic expertise–Standardized assessment–Confirmation of diagnosis

• Management expertise–Choice of an appropriate therapy–Oxygen prescription–Pulmonary rehabilitation–Attention to obesity and sarcopenia/frailty–Potential enrollment in a clinical trial –Transplant evaluation Flaherty et al. Am J Respir Crit Care Med 2004;170:904-10.

Flaherty et al. Am J Respir Crit Care Med 2007;175:1054-60.Lamas et al. Am J Respir Crit Care Med 2011;184:842-7.

ILD Checklist

• Therapeutic options x• Supplemental oxygen• Age-appropriate vaccinations • Risk factor reduction x• Pulmonary rehabilitation x• Clinical trials x• Lung transplant evaluation x• Patient education • Advocacy group involvement

x• Mental health needs x

ReferralOpportunity?

Delayed Care Associated with Higher Mortality

Lamas et al. Am J Respir Crit Care Med. 2011;184:842-847.

P for trend = 0.04

Lung Transplantation is Increasing

http://www.ishlt.org/registries/slides.asp?slides=heartLungRegistry. Accessed August 2014.

19901991

19921993

19941995

19961997

19981999

20002001

20022003

20042005

20062007

20082009

20102011

0

500

1,000

1,500

2,000

2,500

3,000CF IPF COPD Alpha-1 IPAH Re-Tx

Num

ber o

f Tra

nspl

ants

IPF

CF

COPD

Lung Transplantation for IPF:2014 Referral Guidelines

• Histopathologic or radiographic evidence of usual interstitial pneumonitis (UIP)

• Abnormal lung function: FVC < 80% predicted or DLCO < 40% predicted

• Any dyspnea or functional limitation attributable to lung disease

• Any oxygen requirement, even if only during exertion

Weill D, et al. J Heart Lung Transplant.2014 Jun 26. [Epub ahead of print].

Conclusions

• Pirfenidone and nintedanib are FDA approved for treatment of IPF

• Diagnosis of IPF requires a patient history, physical exam, lab tests, HRCT, and sometimes a biopsy

• Patients should be referred early –Pulmonary rehabilitation– ILD center– Lung transplantation evaluation

To Receive Credit for this Activity:Please Complete the Evaluation and Posttest

at www.pilotforipf.org/credit/##

Supplemental Slides

Possible NAC Mechanisms of Action

• Increase glutathione antioxidation • Downregulate lysyl oxidase (LOX) activity,

(essential for collagen deposition)

Li S, et al. Respiration. 2012;84(6):509-517.Rushworth GF, et al. Pharmacol Ther. 2014;141(2):150-159.

Demedts M, et al. New Engl J Med. 2005;353:2229-2242.

+ azathioprine + steroids

+ azathioprine + steroids

Early Evidence for a NAC Cocktail

Acetylcysteine + azathioprine + steroids

Placebo + azathioprine + steroids

ATS 2011

2011-2013 2014Pre-2011

PANTHER 2012

Raghu G, et al. N Engl J Med. 2012;366:1968-1977.

ATS 2011

2011-2013 2014Pre-2011

PANTHER 2012 Interim Results

• Triple therapy has no benefit for FVC

• Increased risk of death

Primary Triple Therapy Placebo P-value

FVC (liters) -0.24 -0.23 0.85


Prob

abili

ty

Time to DeathKaplan–Meier Analysis

Weeks Since Randomization

HR 9.26 (95% CI 1.16-74.1)

P = 0.01

ATS 2011

2011-2013 2014Pre-2011

PANTHER 2012 Adverse Events

Death

Respira

tory Dea

th

Hospita

lization

Acute

Exac

erbati

on

Serio

us Adve

rse Ev

ent

05

101520253035

Placebo Pred/Aza/NAC

• Triple therapy has higher incidence of adverse events than placebo

P-value for each comparison < 0.05

IPFNet writing committee. N Engl J Med 2012;366;1968-77.

P-values < 0.05


Perc

enta

ge

ATS 2011

2011-2013 2014Pre-2011

PANTHER 2012 Conclusions

• Compelling evidence against the use of the triple combination for patients with mild-to-moderate IPF

• Next steps–Combination arm terminated–Two arms of study continued (NAC vs placebo)



PANTHER 2014ATS

20112011-2013Pre-2011 2014

• Subjects: 264 patients with IPF (2 arm continuation of PANTHER-IPF)

• Treatment: acetylcysteine (600 mg) or placebo 3 times daily

• Duration: 60 weeks• Primary end point: change in FVC • Secondary end points

– Time to the first acute exacerbation – Change from baseline in the total score on the St.

George’s Respiratory Questionnaire

PANTHER Study Design


To Receive Credit for this Activity, Please Complete the Evaluation and Posttest:

PILOTforIPF.org/credit/13

a new era in ipf: trials and treatments craig thurm, md director, pulmonary medicine director,...

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