Trial Outcomes & Findings for Open Label Extension Study in Patients With Idiopathic Pulmonary Fibrosis Who Completed Protocol AC-052-321/ BUILD 3 / NCT00391443 (NCT NCT00631475)

NCT ID: NCT00631475

Last Updated: 2025-02-04

Results Overview

Mean extent of exposure to bosentan treatment in months

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 128 participants
• Primary outcome timeframe: Start of study to end of study, up to 21 months
• Results posted on: 2025-02-04

Participant Flow

Patients were enrolled at 61 centers in 15 countries (Australia, Belgium, Canada, Czech Republic, France, Germany, Ireland, Israel, Italy, Japan, South Korea, , Spain, Switzerland, UK, and USA. The first patient started on 5 March 2008 and the last patient, last visit was on 01 April 2010.

In total, 128 of the 615 patients who received randomized treatment in BUILD 3 (NCT00391443) rolled over into the BUILD 3 OL extension.

Participant milestones

Measure	Bosentan Treatment Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Overall Study STARTED	128
Overall Study COMPLETED	83
Overall Study NOT COMPLETED	45

Reasons for withdrawal

Measure	Bosentan Treatment Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Overall Study Death	18
Overall Study Adverse Event	14
Overall Study Withdrew consent	5
Overall Study Preparation for lung transplant	8

Baseline Characteristics

Open Label Extension Study in Patients With Idiopathic Pulmonary Fibrosis Who Completed Protocol AC-052-321/ BUILD 3 / NCT00391443

Baseline characteristics by cohort

Measure	Bosentan Treatment n=128 Participants Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Age, Continuous	65.4 years STANDARD_DEVIATION 8.2 • n=5 Participants
Age, Customized 18-40 years	1 participants n=5 Participants
Age, Customized 41-60 years	33 participants n=5 Participants
Age, Customized 61-70 years	62 participants n=5 Participants
Age, Customized >70 years	32 participants n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	97 Participants n=5 Participants
Region of Enrollment Australia	12 participants n=5 Participants
Region of Enrollment Belgium	1 participants n=5 Participants
Region of Enrollment Canada	14 participants n=5 Participants
Region of Enrollment Czech Republic	1 participants n=5 Participants
Region of Enrollment France	3 participants n=5 Participants
Region of Enrollment Germany	11 participants n=5 Participants
Region of Enrollment Ireland	1 participants n=5 Participants
Region of Enrollment Israel	4 participants n=5 Participants
Region of Enrollment Italy	2 participants n=5 Participants
Region of Enrollment Japan	8 participants n=5 Participants
Region of Enrollment Korea, Republic of	5 participants n=5 Participants
Region of Enrollment Spain	8 participants n=5 Participants
Region of Enrollment Switzerland	4 participants n=5 Participants
Region of Enrollment United Kingdom	3 participants n=5 Participants
Region of Enrollment United States	51 participants n=5 Participants

PRIMARY outcome

Timeframe: Start of study to end of study, up to 21 months

Population: For two patients, the exact treatment stop date was missing and the duration could not be calculated, but these patients received at least 345 and 127 days of open label (OL) treatment.

Mean extent of exposure to bosentan treatment in months

Outcome measures

Measure	Bosentan Treatment n=126 Participants Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Extent of Exposure to Bosentan in Patients With Idiopathic Pulmonary Fibrosis (IPF)	6.4 months Standard Deviation 4.6

SECONDARY outcome

Timeframe: Start to end of study, up to 21 months

Population: For two patients, the exact treatment stop date was missing and the duration could not be calculated, but these patients received at least 345 and 127 days of OL treatment, respectively.

Numbers of participants exposed to bosentan treatment over time

Outcome measures

Measure	Bosentan Treatment n=126 Participants Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Number of Patients Exposed to Bosentan Over Time For at least 4 months	74 Participants
Number of Patients Exposed to Bosentan Over Time For at least 8 months	44 Participants
Number of Patients Exposed to Bosentan Over Time For at least 12 months	17 Participants
Number of Patients Exposed to Bosentan Over Time For at least 16 months	7 Participants
Number of Patients Exposed to Bosentan Over Time For at least 20 months	2 Participants

SECONDARY outcome

Timeframe: Start to end of study, up to 21 months

Population: Study population

Number of participants with at least one AE that led to permanent discontinuation of study treatment.

Outcome measures

Measure	Bosentan Treatment n=128 Participants Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Adverse Events (AE) Leading to Discontinuation of Study Drug.	32 participants

SECONDARY outcome

Timeframe: up to 21 months plus 28 days after the end of study drug

Population: Study population

Number of participants with at least one SAE during the study.

Outcome measures

Measure	Bosentan Treatment n=128 Participants Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Treatment-emergent Serious Adverse Events (SAE)	51 participants

SECONDARY outcome

Timeframe: up to 21 months, plus 24 hours after the end of study treatment

Population: Study population

Number of participants with an increase in ALT and/or AST to > 3 times upper limit of normal during the study.

Outcome measures

Measure	Bosentan Treatment n=128 Participants Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Occurrence of Liver Function Test (LFT: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)) Abnormality.	3 participants

Adverse Events

Bosentan Treatment

Serious events: 51 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bosentan Treatment n=128 participants at risk Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	18.0% 23/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.1% 4/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 3/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Lower respiratory tract infection	3.1% 4/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Pneumonia	3.1% 4/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Bronchitis	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Chronic sinusitis	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Diverticulitis	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Lobar pneumonia	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Respiratory tract infection viral	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Septic shock	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Sinusitis	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Infections and infestations Viral infection	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Cardiac disorders Coronary artery disease	1.6% 2/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Cardiac disorders Arrhythmia	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Cardiac disorders Atrial flutter	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Cardiac disorders Cardiac arrest	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Cardiac disorders Cardiopulmonary failure	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Cardiac disorders Right ventricular failure	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Hepatobiliary disorders Cholecystitis	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Hepatobiliary disorders Hepatic failure	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Hepatobiliary disorders Ischaemic hepatitis	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Investigations Blood iron decreased	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Investigations Hepatic enzyme increased	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Investigations Liver function test abnormal	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Surgical and medical procedures Lung transplant	2.3% 3/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Gastrointestinal disorders Abdominal pain	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
General disorders General physical health deterioration	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
General disorders Pyrexia	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Injury, poisoning and procedural complications Anastomotic stenosis	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Injury, poisoning and procedural complications Rib fracture	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Renal and urinary disorders Renal colic	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Renal and urinary disorders Renal failure acute	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Vascular disorders Deep vein thrombosis	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Vascular disorders Hypotension	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Nervous system disorders Cerebrovascular accident	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Psychiatric disorders Suicide attempt	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.

Other adverse events

Measure	Bosentan Treatment n=128 participants at risk Oral bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks, and oral bosentan 125 mg b.i.d. (62.5 mg b.i.d. if \</= 40 kg) thereafter
Investigations LIVER FUNCTION TEST ABNORMAL	1.6% 2/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
Respiratory, thoracic and mediastinal disorders IDIOPATHIC PULMONARY FIBROSIS	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.
General disorders OEDEMA PERIPHERAL	0.78% 1/128 • Up to 28 days after the end of study drug Only adverse events leading to premature discontinuation of study treatment were reported during the study. All serious adverse events occurring during and up to 28 days after end-of-study treatment were reported. Events listed as idiopathic pulmonary fibrosis were reported as worsening of idiopathic pulmonary fibrosis.

Additional Information

Isabelle Leconte, PhD/Data Science Group Leader, Director

Actelion Pharmaceuticals Ltd

Phone: + 41 61 565 64 18

Email: isabelle.leconte@actelion.com

Results disclosure agreements

• Principal investigator is a sponsor employee Actelion, with steering committee, shall complete the review and provide any modifications required to protect Actelion's patent rights and confidential information within sixty (60) days of receipt of the proposed publication. During this period, Investigator shall not permit publication. If Actelion reasonably anticipates filing a patent application claiming an invention arising out of the Study, such publication shall be delayed until after the application is filed.
• Publication restrictions are in place

Restriction type: OTHER