Trial Outcomes & Findings for Celecoxib and Radiation Therapy in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer (NCT NCT00046839)

Last Updated: 2015-11-17

Results Overview

Patients were followed for at least 90 days from start of RT and carefully evaluated with respect to treatment morbidity. A dose limiting toxicity (DLT) was defined as grade 3 or 4 nonhematologic (excluding nausea, vomiting, and alopecia) and grade 4 hematologic toxicities. Six patients were to be accrued at each dose level. If no more than three of the six patients experienced a DLT then that dose level was considered acceptable and dose escalation occurred by accruing six more patients at the next dose level. Otherwise, the preceding dose level, if any, would be declared the MTD. The MTD would be used for the Phase II arm. At a given dose, the probability of halting dose escalation when the true toxicity is 50% or higher is at least 66% (power). In addition, if the true DLT rate is instead 20%, there will still be a 10% probability of halting dose escalation at a given dose level (type I error). Rating scale: 0 = not the MTD, 1 = MTD

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

21 participants

Primary outcome timeframe

Start of treatment to 90 days

Results posted on

2015-11-17

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental: Phase I: Celecoxib 200mg BID + RT COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.	Experimental: Phase I/II: Celecoxib 400mg BID + RT COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.
Overall Study STARTED	8	13
Overall Study COMPLETED	7	11
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental: Phase I: Celecoxib 200mg BID + RT COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.	Experimental: Phase I/II: Celecoxib 400mg BID + RT COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.
Overall Study Ineligible / No protocol treatment	0	2
Overall Study Withdrawal of consent	1	0

Baseline Characteristics

Celecoxib and Radiation Therapy in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Phase I: Celecoxib 200mg BID + RT n=7 Participants COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.	Experimental: Phase I/II: Celecoxib 400mg BID + RT n=11 Participants COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.	Total n=18 Participants Total of all reporting groups
Age, Continuous	73 years n=99 Participants	71 years n=107 Participants	72 years n=206 Participants
Sex: Female, Male Female	6 Participants n=99 Participants	8 Participants n=107 Participants	14 Participants n=206 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants

PRIMARY outcome

Timeframe: Start of treatment to 90 days

Population: The first six eligible patients who started protocol treatment at each dose level.

Outcome measures

Outcome measures
Measure	Phase I: Celecoxib 200mg BID + RT n=6 Participants COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy. celecoxib radiation therapy	Phase I: Celecoxib 400mg BID + RT n=6 Participants COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy. celecoxib radiation therapy
Maximum Tolerated Dose (MTD) of Celecoxib Combined With Radiation Therapy (RT)	0 units on a scale	1 units on a scale

PRIMARY outcome

Timeframe: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 12 months.

Population: Eligible patients who started protocol treatment.

Because only 21 patients (18 analyzable) out of 128 planned were accrued on this study, all analyzable patients were combined to report overall survival. The original study design planned for a comparison to a historical control, but due to the small number of patients, survival time is only reported, not tested.

Outcome measures

Outcome measures
Measure	Phase I: Celecoxib 200mg BID + RT n=18 Participants COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy. celecoxib radiation therapy	Phase I: Celecoxib 400mg BID + RT COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy. celecoxib radiation therapy
Overall Survival	10.0 years Interval 6.1 to 16.7	—

Adverse Events

Experimental: Phase I: Celecoxib 200mg BID + RT

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Experimental: Phase I/II: Celecoxib 400mg BID + RT

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Experimental: Phase I: Celecoxib 200mg BID + RT n=7 participants at risk COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.	Experimental: Phase I/II: Celecoxib 400mg BID + RT n=11 participants at risk COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.
Cardiac disorders Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Infections and infestations Infection without neutropenia	0.00% 0/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).

Other adverse events

Additional Information

Wendy Seiferheld

Radiation Therapy Oncology Group (RTOG)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Experimental: Phase I: Celecoxib 200mg BID + RT n=7 participants at risk COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.	Experimental: Phase I/II: Celecoxib 400mg BID + RT n=11 participants at risk COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression. Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.
Blood and lymphatic system disorders Hematologic-Other	28.6% 2/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Blood and lymphatic system disorders Hemoglobin (Hgb)	28.6% 2/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Dyspepsia/heartburn	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Dysphagia, esophagitis, odynophagia (painful swallowing)	42.9% 3/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Dysphagia-esophageal related to radiation	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Dysphagia-pharyngeal related to radiation	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Nausea	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	18.2% 2/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Vomiting	0.00% 0/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Edema	0.00% 0/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Fatigue (lethargy, malaise, asthenia)	57.1% 4/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	36.4% 4/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Lung	28.6% 2/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Other	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Skin (within the irradiated field)	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Injury, poisoning and procedural complications Radiation dermatitis	42.9% 3/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	27.3% 3/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Creatinine	42.9% 3/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Leukocytes (total WBC)	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Lymphopenia	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Metabolic-Other	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Neutrophils/granulocytes (ANC/AGC)	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations SGPT (ALT)	28.6% 2/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Weight loss	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Anorexia	0.00% 0/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Hyperglycemia	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Hyperkalemia	28.6% 2/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Hypernatremia	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Hypocalcemia	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Hypoglycemia	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Musculoskeletal and connective tissue disorders Arthralgia (joint pain)	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Nervous system disorders Headache	0.00% 0/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Nervous system disorders Neuropathy motor	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Nervous system disorders Neuropathy-sensory	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Psychiatric disorders Confusion	0.00% 0/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Renal and urinary disorders Renal/GU-Other	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.1% 1/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Skin and subcutaneous tissue disorders Pigmentation changes (e.g., vitiligo)	14.3% 1/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Skin and subcutaneous tissue disorders Pruritus	28.6% 2/7 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/11 Subjects experiencing more than one of a given SAE (serious adverse event) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).