Three-Arm Study of the Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis

NCT ID: NCT00287716

Last Updated: 2017-05-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

435 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-07-14

Study Completion Date

2008-11-10

Brief Summary

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The objectives of this study are to assess the safety and efficacy of treatment with pirfenidone 2403 milligrams per day (mg/d) compared with placebo in patients with idiopathic pulmonary fibrosis (IPF), to assess the safety and efficacy of treatment with pirfenidone 1197 mg/d in patients with idiopathic pulmonary fibrosis and to characterize the pharmacokinetic disposition of pirfenidone in patients with idiopathic pulmonary fibrosis.

Detailed Description

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This is a Phase 3, randomized, double blind, placebo-controlled, three-arm, safety and efficacy study of pirfenidone in patients with idiopathic pulmonary fibrosis. Approximately 400 patients at approximately 70 centers will be randomly assigned (2:2:1) to receive either 2403 milligrams (mg) of pirfenidone, placebo equivalent, or 1197 mg of pirfenidone administered in divided doses three times per day (TID) with food. Patients will be randomized by geographic region.

Patients will receive blinded study treatment from the time of randomization until the last patient randomized has been treated for 72 weeks. A Data Monitoring Committee (DMC) will periodically review safety and efficacy data to ensure patient safety.

After week 72, patients who meet the Progression of Disease (POD) definition, which is a ≥ 10% absolute decrease in percent predicted FVC or a ≥ 15% absolute decrease in percent predicted carbon monoxide diffusing capacity (DLco), will be eligible to receive permitted IPF therapies in addition to their blinded study drug. Permitted IPF therapies include corticosteroids, azathioprine, cyclophosphamide and N-acetyl-cysteine (with restrictions).

Conditions

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Idiopathic Pulmonary Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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2403 mg/day pirfenidone

Active arm 1, 2403 mg/day pirfenidone dose group.

Group Type ACTIVE_COMPARATOR

Pirfenidone

Intervention Type DRUG

1197 or 2403 mg/day given orally, and administered in divided doses three times daily with food, for the duration of the study.

1197 mg/day pirfenidone

Active arm 2, 1197 mg/day pirfenidone.

Group Type ACTIVE_COMPARATOR

Pirfenidone

Intervention Type DRUG

1197 or 2403 mg/day given orally, and administered in divided doses three times daily with food, for the duration of the study.

placebo

Placebo equivalent.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo equivalent, given orally, and administered in divided doses three times daily with food, for the duration of the study.

Interventions

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Pirfenidone

1197 or 2403 mg/day given orally, and administered in divided doses three times daily with food, for the duration of the study.

Intervention Type DRUG

Placebo

Placebo equivalent, given orally, and administered in divided doses three times daily with food, for the duration of the study.

Intervention Type DRUG

Eligibility Criteria

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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

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
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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InterMune, Inc.

Brisbane, California, United States

Site Status

Countries

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United States

References

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Behr J, Nathan SD, Costabel U, Albera C, Wuyts WA, Glassberg MK, Haller H Jr, Alvaro G, Gilberg F, Samara K, Lancaster L. Efficacy and Safety of Pirfenidone in Advanced Versus Non-Advanced Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Six Clinical Studies. Adv Ther. 2023 Sep;40(9):3937-3955. doi: 10.1007/s12325-023-02565-3. Epub 2023 Jun 30.

Reference Type DERIVED
PMID: 37391667 (View on PubMed)

Allen RJ, Stockwell A, Oldham JM, Guillen-Guio B, Schwartz DA, Maher TM, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV; International IPF Genetics Consortium. Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis. Thorax. 2022 Aug;77(8):829-833. doi: 10.1136/thoraxjnl-2021-218577. Epub 2022 Jun 10.

Reference Type DERIVED
PMID: 35688625 (View on PubMed)

Kreuter M, Lee JS, Tzouvelekis A, Oldham JM, Molyneaux PL, Weycker D, Atwood M, Kirchgaessler KU, Maher TM. Monocyte Count as a Prognostic Biomarker in Patients with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2021 Jul 1;204(1):74-81. doi: 10.1164/rccm.202003-0669OC.

Reference Type DERIVED
PMID: 33434107 (View on PubMed)

Glassberg MK, Nathan SD, Lin CY, Morgenthien EA, Stauffer JL, Chou W, Noble PW. Cardiovascular Risks, Bleeding Risks, and Clinical Events from 3 Phase III Trials of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. Adv Ther. 2019 Oct;36(10):2910-2926. doi: 10.1007/s12325-019-01052-y. Epub 2019 Aug 10.

Reference Type DERIVED
PMID: 31401786 (View on PubMed)

Nathan SD, Costabel U, Albera C, Behr J, Wuyts WA, Kirchgaessler KU, Stauffer JL, Morgenthien E, Chou W, Limb SL, Noble PW. Pirfenidone in patients with idiopathic pulmonary fibrosis and more advanced lung function impairment. Respir Med. 2019 Jul;153:44-51. doi: 10.1016/j.rmed.2019.04.016. Epub 2019 Apr 24.

Reference Type DERIVED
PMID: 31153107 (View on PubMed)

Kreuter M, Lederer DJ, Molina-Molina M, Noth I, Valenzuela C, Frankenstein L, Weycker D, Atwood M, Kirchgaessler KU, Cottin V. Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis. Chest. 2019 Oct;156(4):706-714. doi: 10.1016/j.chest.2019.04.015. Epub 2019 Apr 29.

Reference Type DERIVED
PMID: 31047956 (View on PubMed)

Nathan SD, Costabel U, Glaspole I, Glassberg MK, Lancaster LH, Lederer DJ, Pereira CA, Trzaskoma B, Morgenthien EA, Limb SL, Wells AU. Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis. Chest. 2019 Apr;155(4):712-719. doi: 10.1016/j.chest.2018.11.008. Epub 2018 Nov 22.

Reference Type DERIVED
PMID: 30472023 (View on PubMed)

Nathan SD, Lancaster LH, Albera C, Glassberg MK, Swigris JJ, Gilberg F, Kirchgaessler KU, Limb SL, Petzinger U, Noble PW. Dose modification and dose intensity during treatment with pirfenidone: analysis of pooled data from three multinational phase III trials. BMJ Open Respir Res. 2018 Aug 2;5(1):e000323. doi: 10.1136/bmjresp-2018-000323. eCollection 2018.

Reference Type DERIVED
PMID: 30116539 (View on PubMed)

Neighbors M, Cabanski CR, Ramalingam TR, Sheng XR, Tew GW, Gu C, Jia G, Peng K, Ray JM, Ley B, Wolters PJ, Collard HR, Arron JR. Prognostic and predictive biomarkers for patients with idiopathic pulmonary fibrosis treated with pirfenidone: post-hoc assessment of the CAPACITY and ASCEND trials. Lancet Respir Med. 2018 Aug;6(8):615-626. doi: 10.1016/S2213-2600(18)30185-1. Epub 2018 Jun 29.

Reference Type DERIVED
PMID: 30072107 (View on PubMed)

Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402. doi: 10.1513/AnnalsATS.201606-458OC.

Reference Type DERIVED
PMID: 28388260 (View on PubMed)

Kreuter M, Bonella F, Maher TM, Costabel U, Spagnolo P, Weycker D, Kirchgaessler KU, Kolb M. Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis. Thorax. 2017 Feb;72(2):148-153. doi: 10.1136/thoraxjnl-2016-208819. Epub 2016 Oct 5.

Reference Type DERIVED
PMID: 27708114 (View on PubMed)

Nathan SD, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, Glasscock KF, King TE Jr, Lancaster L, Lederer DJ, Lin Z, Pereira CA, Swigris JJ, Valeyre D, Noble PW, Wells AU. Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis. Thorax. 2016 May;71(5):429-35. doi: 10.1136/thoraxjnl-2015-207011. Epub 2016 Mar 11.

Reference Type DERIVED
PMID: 26968970 (View on PubMed)

Lancaster L, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, King TE Jr, Lederer DJ, Lin Z, Nathan SD, Pereira CA, Swigris JJ, Valeyre D, Noble PW. Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. BMJ Open Respir Res. 2016 Jan 12;3(1):e000105. doi: 10.1136/bmjresp-2015-000105. eCollection 2016.

Reference Type DERIVED
PMID: 26835133 (View on PubMed)

Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, King TE Jr, Lancaster L, Sahn SA, Szwarcberg J, Valeyre D, du Bois RM; CAPACITY Study Group. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011 May 21;377(9779):1760-9. doi: 10.1016/S0140-6736(11)60405-4. Epub 2011 May 13.

Reference Type DERIVED
PMID: 21571362 (View on PubMed)

Other Identifiers

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Capacity 2

Identifier Type: -

Identifier Source: secondary_id

PIPF-004

Identifier Type: -

Identifier Source: org_study_id

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