Phase IV, Open-label, Multicenter Study of Dasatinib in Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients With Chronic, Low-grade Non-Hematologic Toxicity to Imatinib

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01660906
• Collaborator: (none)
• Enrollment: 39
• Locations: 22
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study proposes to evaluate the number of chronic, Grade 1 or 2, non-hematologic Adverse Events (AEs) that reduce in grade or resolve at 3 months after switching therapy from imatinib to dasatinib.

Condition or Disease	Intervention/Treatment	Phase
Chronic Phase Chronic Myeloid Leukemia	Drug: Dasatinib	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Open-label, Multicenter Study of Dasatinib in Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients With Chronic, Low-grade Non-Hematologic Toxicity to Imatinib
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib (100 mg)	Drug: Dasatinib; tablets, oral, 100 mg, Once daily, Up to12 months on study,; Other Names: Sprycel

Outcome Measures

Primary Outcome Measures

1. The Number of Imatinib-related Adverse Events (AEs) That Were Resolved, Improved, Remained Unchanged, or Worsened After 3 Months of Dasatinib Treatment [3 months after switch to dasatinib]

   Dasatinib treatment was administered and its impact on the imatinib-related Grade 1/2 adverse events was assessed. The severity of an adverse event is ranked based on grades that range from 1 to 4. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4= Potentially Life-threatening or disabling. Resolved, AE no longer present or resolution of imatinib-related chronic Grade 1 or Grade 2 non-hematologic AEs. Improved, AE grade reduced from Grade 2 to Grade 1. Unchanged, AE did not improve or worsen or no change in grade. Worsened, grade Increased.

Secondary Outcome Measures

1. Mean Change From Baseline in Patient Reported CML Symptom Severity and Interference by MD Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Score After Switching to Dasatinib [Baseline to 3, 6, 12 months]

   The MD Anderson Symptom Inventory Chronic Myeloid Leukemia (MDASI-CML) is a validated questionnaire completed by study participants to assess symptom severity and symptom interference on daily function. These categories are divided into 5 domain summary scores: Core Symptom Severity Score, Interference Score, Symptom Severity Score, CML-Specific Symptom Severity Score, and 5 Most Severe Symptom Score. Scores were evaluated at baseline and after switching to Dasatinib on a range from 1 to 10; 1=not present/did not interfere, 10=as bad as you can imagine/interfered completely.

2. Mean Change From Baseline in Patient Reported Quality of Life Measurements by The European Organization for Research and Treatment of Cancer - Quality of Life (QoL) Questionnaire (EORTC QLQ) Score After Switching to Dasatinib [Baseline to 6, 12 months]

   The EORTC QLQ-C30 questionnaire is completed by study participants to assess quality of life through nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social functioning); three symptom scales (fatigue, pain and nausea/vomiting); and a global health status/QoL scale. Six single-item scales are also included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures were evaluated at baseline and after switching to Dasatinib as an average raw score that was standardized by transformation, so that final scores were on a range in score from 0 to 100. A high score for a functional scale represents a healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale and single-item measures represents a high level of problematic symptomatology.

3. Number of Participants With at Least 1 AE, Discontinuations Due to AE, Treatment-related AE, Serious Adverse Event (SAE), Treatment-related SAE, or Death as Outcome [Date of first dose to 30 post last dose of study drug, an average of 3 years]

   SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Treatment-related=having certain, probable, possible, or missing relationship to study drug, dasatinib.

4. The Percentage of Participants With at Least 1 Imatinib-related Grade 1 or Grade 2 Chronic Adverse Events (AEs) That Improved Without Worsening Within 3 Months of Switching to Dasatinib [3 months]

   Dasatinib treatment was administered and its impact on the Imatinib-related Grade 1/2 adverse events was assessed. The percentage of participants is based on the number that had pre-existing Imatinib-related AEs. Measure assesses the participants with reduction or improvement of at least 1 Imatinib-related Grade 1 or Grade 2 chronic AE, without a worsening of any Imatinib-related, chronic adverse events after Dasatinib treatment. The severity of an adverse event is ranked based on grades that range from 1 to 4. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4= Potentially Life-threatening or disabling. Improved, AE grade reduced from Grade 2 to Grade 1. Worsened, Grade Increased. Confidence interval from Clopper-Pearson method.

Other Outcome Measures

1. Number of Participants With a Major Molecular Response (MMR) and MR 4.5 After Switching to Dasatinib [6 and 12 months]

   Molecular responses were assessed at 6 and 12 months after switching to dasatinib to determine if these baseline responses could be maintained. MR4.5, the number of treated participants with BCR-ABL transcripts ≤ 0.0032% (IS) at 6 and 12 months from the date of dasatinib initiation; MMR, Major Molecular Response = 3-log reduction in BCR-ABL gene transcripts from a standardized baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with CML-CP patients achieving an optimal response to imatinib treatment with Grade 1 or 2 non-hematologic adverse events persisting for at least 2 months or recurring at least 3 times in the preceding 12 months, despite best supportive care

• Men and women with Chronic Myeloid Leukemia- Chronic Phase (CML-CP) Ph+ ≥ age 18

• Daily Eastern Co-Operative Group (ECOG) performance status = 0 - 2

• Patient willing and able to give informed consent

• Life expectancy > 6 months

• Adequate renal function

• Adequate hepatic function

Exclusion Criteria:

• Patients who are pregnant or breast feeding

• Men whose partner is unwilling to avoid pregnancy.

• Previous treatment with any other tyrosine-kinase inhibitor (TKI), except for imatinib

• Current grade 3 or 4 imatinib related adverse event

• Prior documented T315I mutation

• Prior diagnosis of accelerated phase or blast crisis CML

• Previous loss of complete hematologic response (CHR) or major cytogenetic response (MCyR) on imatinib

• Concurrent medical condition of uncontrolled infection, cardiovascular diseases of cardiac failure, congenital long QT syndrome, ventricular arrhythmias, prolonged QT interval, second or third degree heart block, uncontrolled angina, myocardial infarction (MI) in the last 6 months, uncontrolled hypertension, pulmonary arterial hypertension, pleural or pericardial effusions, or history of bleeding disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Cancer Medical Center	Anaheim	California	United States	92801
2	Cancer Center Of Central Connecticut	Southington	Connecticut	United States	06489
3	St. Agnes Healthcare, Inc.	Baltimore	Maryland	United States	21229
4	Promedica Hematology & Oncology Assoicates	Sylvania	Ohio	United States	43560
5	The University Of Texas Md Anderson Cancer Center	Houston	Texas	United States	77030
6	Local Institution	Creteil Cedex		France	94010
7	Local Institution	Lille CEDEX		France	59037
8	Local Institution	Pierre Benite cedex		France	69495
9	Local Institution	Pringy Cedex		France	74374
10	Local Institution	Vandoeuvre les Nancy		France	54511
11	Local Institution	Jena		Germany	07747
12	Local Institution	Koln		Germany	50937
13	Local Institution	Lubeck		Germany	23562
14	Local Institution	Mannheim		Germany	68169
15	Local Institution	Rostock		Germany	18055
16	Local Institution	Catania		Italy	95124
17	Local Institution	Firenze		Italy	50134
18	Local Institution	Napoli		Italy	80131
19	Local Institution	Roma		Italy	00144
20	Local Institution	Roma		Italy	00161
21	Local Institution	Torino		Italy	10126
22	Local Institution	Seoul		Korea, Republic of	137-701

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01660906
• Other Study ID Numbers: CA180-400; 2011-006180-21
• First Posted: Aug 9, 2012
• Last Update Posted: Nov 22, 2016
• Last Verified: Nov 1, 2016

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Dasatinib

Study Results

Participant Flow

Pre-assignment Detail	39 participants enrolled and were treated.

Arm/Group Title	Dasatinib (100 mg)
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
Period Title: Overall Study
STARTED	39
COMPLETED	36
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Dasatinib (100 mg)
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
Overall Participants	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.1 (15.13)
Age, Customized (Count of Participants)
< 65 years	27 69.2%
>= 65 years	12 30.8%
Gender (Count of Participants)
Female	18 46.2%
Male	21 53.8%
Race/Ethnicity, Customized (Count of Participants)
White	12 30.8%
Black or African American	1 2.6%
American Indian or Alaska Native	0 0%
Asian	22 56.4%
Native Hawaiian or Other Pacific Islander	0 0%
Other	4 10.3%
Median Time Since CML-CP Diagnosis (months) [Median (Full Range) ]
Median (Full Range) [months]	51.3
Median Duration of Imatinib Treatment (months) [Median (Full Range) ]
Median (Full Range) [months]	51.2
Imatinib Dose at Baseline (Count of Participants)
< 400 milligrams	19 48.7%
400 milligrams	20 51.3%
Best Baseline Response (Count of Participants)
MR4.5	10 25.6%
MMR	20 51.3%
CCyR	4 10.3%
PCyR	2 5.1%
Cytogenetic Test Not Performed	3 7.7%

Outcome Measures

1. Primary Outcome

Title	The Number of Imatinib-related Adverse Events (AEs) That Were Resolved, Improved, Remained Unchanged, or Worsened After 3 Months of Dasatinib Treatment
Description	Dasatinib treatment was administered and its impact on the imatinib-related Grade 1/2 adverse events was assessed. The severity of an adverse event is ranked based on grades that range from 1 to 4. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4= Potentially Life-threatening or disabling. Resolved, AE no longer present or resolution of imatinib-related chronic Grade 1 or Grade 2 non-hematologic AEs. Improved, AE grade reduced from Grade 2 to Grade 1. Unchanged, AE did not improve or worsen or no change in grade. Worsened, grade Increased.
Time Frame	3 months after switch to dasatinib

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Dasatinib (100 mg)
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
Measure Participants	39
Resolved	91
Improved	2
Unchanged	27
Worsened	1

2. Secondary Outcome

Title	Mean Change From Baseline in Patient Reported CML Symptom Severity and Interference by MD Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Score After Switching to Dasatinib
Description	The MD Anderson Symptom Inventory Chronic Myeloid Leukemia (MDASI-CML) is a validated questionnaire completed by study participants to assess symptom severity and symptom interference on daily function. These categories are divided into 5 domain summary scores: Core Symptom Severity Score, Interference Score, Symptom Severity Score, CML-Specific Symptom Severity Score, and 5 Most Severe Symptom Score. Scores were evaluated at baseline and after switching to Dasatinib on a range from 1 to 10; 1=not present/did not interfere, 10=as bad as you can imagine/interfered completely.
Time Frame	Baseline to 3, 6, 12 months

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Dasatinib (100 mg)
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
Measure Participants	39
Core Symptom Severity Score, Month 3; n=37	-1.35 (1.78)
Core Symptom Severity Score, Month 6; n=36	-1.44 (1.84)
Core Symptom Severity Score, Month 12; n=37	-1.06 (1.87)
Interference Score, Month 3; n=37	-1.24 (2.36)
Interference Score, Month 6; n=35	-1.28 (2.45)
Interference Score, Month 12; n=36	-1.30 (2.56)
Symptom Severity Score, Month 3; n=37	-1.73 (1.80)
Symptom Severity Score, Month 6; n=36	-1.80 (1.85)
Symptom Severity Score, Month 12; n=37	-1.46 (1.75)
CML-specific Symptom Severity Score, Month 3; n=37	-2.52 (2.35)
CML-specific Symptom Severity Score, Month 6; n=36	-2.60 (2.15)
CML-specific Symptom Severity Score,Month 12; n=36	-2.24 (1.87)
5 Most Severe Symptom Score, Month 3; n=37	-1.61 (1.76)
5 Most Severe Symptom Score, Month 6; n=36	-1.69 (1.84)
5 Most Severe Symptom Score, Month 12; n=37	-1.43 (1.72)

3. Secondary Outcome

Title	Mean Change From Baseline in Patient Reported Quality of Life Measurements by The European Organization for Research and Treatment of Cancer - Quality of Life (QoL) Questionnaire (EORTC QLQ) Score After Switching to Dasatinib
Description	The EORTC QLQ-C30 questionnaire is completed by study participants to assess quality of life through nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social functioning); three symptom scales (fatigue, pain and nausea/vomiting); and a global health status/QoL scale. Six single-item scales are also included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures were evaluated at baseline and after switching to Dasatinib as an average raw score that was standardized by transformation, so that final scores were on a range in score from 0 to 100. A high score for a functional scale represents a healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale and single-item measures represents a high level of problematic symptomatology.
Time Frame	Baseline to 6, 12 months

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib (100 mg)
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
Measure Participants	39
Global Health Status/QOL, Month 6; n=36	0.46 (23.733)
Global Health Status/QOL, Month 12; n=35	2.86 (27.782)
Cognitive Functioning, Month 6; n=35	1.90 (20.119)
Cognitive Functioning, Month 12; n=35	1.43 (18.245)
Emotional Functioning, Month 6; n=35	11.19 (23.216)
Emotional Functioning, Month 12; n=35	12.62 (25.595)
Physical Functioning, Month 6; n=36	-1.67 (20.923)
Physical Functioning, Month 12; n=36	0.74 (19.241)
Role Functioning, Month 6; n=36	-4.17 (27.422)
Role Functioning, Month 12; n=36	2.78 (23.401)
Social Functioning, Month 6; n=35	13.81 (26.036)
Social Functioning, Month 12; n=35	14.76 (24.512)
Fatigue, Month 6; n=36	-6.79 (20.102)
Fatigue, Month 12; n=36	-8.33 (21.639)
Nausea and Vomiting, Month 6; n=36	-9.72 (31.966)
Nausea and Vomiting, Month 12; n=36	-4.63 (30.760)
Pain, Month 6; n=36	-2.78 (38.318)
Pain, Month 12; n=36	-8.80 (25.350)
Appetite Loss, Month 6; n=35	1.90 (29.085)
Appetite Loss, Month 12; n=36	1.85 (29.755)
Constipation, Month 6; n=36	-0.93 (28.156)
Constipation, Month 12; n=35	8.57 (23.351)
Diarrhoea, Month 6; n=36	0.00 (36.515)
Diarrhoea, Month 12; n=35	-2.86 (40.722)
Dyspnoea, Month 6; n=36	5.56 (36.947)
Dyspnoea, Month 12; n=36	9.26 (39.530)
Financial Difficulties, Month 6; n=35	-10.48 (21.038)
Financial Difficulties, Month 12; n=35	-13.33 (18.436)
Insomnia, Month 6; n=36	0.93 (42.528)
Insomnia, Month 12; n=36	-1.85 (38.991)

4. Secondary Outcome

Title	Number of Participants With at Least 1 AE, Discontinuations Due to AE, Treatment-related AE, Serious Adverse Event (SAE), Treatment-related SAE, or Death as Outcome
Description	SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Treatment-related=having certain, probable, possible, or missing relationship to study drug, dasatinib.
Time Frame	Date of first dose to 30 post last dose of study drug, an average of 3 years

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Dasatinib (100 mg)
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
Measure Participants	39
At least 1 AE	37 94.9%
Discontinuation due to AE	3 7.7%
Treatment-related AEs	34 87.2%
SAEs	11 28.2%
Treatment-related SAEs	3 7.7%
Death	0 0%

5. Secondary Outcome

Title	The Percentage of Participants With at Least 1 Imatinib-related Grade 1 or Grade 2 Chronic Adverse Events (AEs) That Improved Without Worsening Within 3 Months of Switching to Dasatinib
Description	Dasatinib treatment was administered and its impact on the Imatinib-related Grade 1/2 adverse events was assessed. The percentage of participants is based on the number that had pre-existing Imatinib-related AEs. Measure assesses the participants with reduction or improvement of at least 1 Imatinib-related Grade 1 or Grade 2 chronic AE, without a worsening of any Imatinib-related, chronic adverse events after Dasatinib treatment. The severity of an adverse event is ranked based on grades that range from 1 to 4. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4= Potentially Life-threatening or disabling. Improved, AE grade reduced from Grade 2 to Grade 1. Worsened, Grade Increased. Confidence interval from Clopper-Pearson method.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Dasatinib (100 mg)
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
Measure Participants	39
Number (95% Confidence Interval) [percentage of participants]	87.1 223.3%

6. Other Pre-specified Outcome

Title	Number of Participants With a Major Molecular Response (MMR) and MR 4.5 After Switching to Dasatinib
Description	Molecular responses were assessed at 6 and 12 months after switching to dasatinib to determine if these baseline responses could be maintained. MR4.5, the number of treated participants with BCR-ABL transcripts ≤ 0.0032% (IS) at 6 and 12 months from the date of dasatinib initiation; MMR, Major Molecular Response = 3-log reduction in BCR-ABL gene transcripts from a standardized baseline.
Time Frame	6 and 12 months

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Dasatinib (100 mg)
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
Measure Participants	39
MMR, Month 6	13 33.3%
MMR, Month 12	13 33.3%
MR4.5, Month 6	18 46.2%
MR4.5, Month 12	22 56.4%

Adverse Events

Time Frame	Date of fist dose of study drug to 30 days post discontinuation of the last dose, an average of 3 years
Adverse Event Reporting Description	Study initiated: December 2012; Study Completion: October 2015
Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib: A 100 mg tablet was taken orally once a day for up to 12 months while on study.
All Cause Mortality
	Dasatinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dasatinib
	Affected / at Risk (%)	# Events
Total	11/39 (28.2%)
Gastrointestinal disorders
Haemorrhoids	2/39 (5.1%)
Anal fissure	1/39 (2.6%)
General disorders
Pyrexia	1/39 (2.6%)
Infections and infestations
Pneumonia	2/39 (5.1%)
Appendicitis	1/39 (2.6%)
Upper respiratory tract infection	1/39 (2.6%)
Injury, poisoning and procedural complications
Rib fracture	1/39 (2.6%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	2/39 (5.1%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/39 (5.1%)
Pulmonary oedema	1/39 (2.6%)
Pneumothorax	1/39 (2.6%)
Pulmonary arterial hypertension	1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	Dasatinib
	Affected / at Risk (%)	# Events
Total	36/39 (92.3%)
Blood and lymphatic system disorders
Anaemia	5/39 (12.8%)
Cardiac disorders
Left ventricular hypertrophy	2/39 (5.1%)
Pericardial effusion	3/39 (7.7%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	2/39 (5.1%)
Nausea	8/39 (20.5%)
Vomiting	3/39 (7.7%)
Constipation	4/39 (10.3%)
Diarrhoea	11/39 (28.2%)
General disorders
Asthenia	2/39 (5.1%)
General physical health deterioration	2/39 (5.1%)
Fatigue	10/39 (25.6%)
Face oedema	2/39 (5.1%)
Pyrexia	6/39 (15.4%)
Infections and infestations
Bronchitis	3/39 (7.7%)
Investigations
Blood urea increased	2/39 (5.1%)
Blood creatinine increased	3/39 (7.7%)
Alanine aminotransferase increased	2/39 (5.1%)
Metabolism and nutrition disorders
Hyperuricaemia	3/39 (7.7%)
Musculoskeletal and connective tissue disorders
Myalgia	2/39 (5.1%)
Tendonitis	2/39 (5.1%)
Musculoskeletal pain	3/39 (7.7%)
Pain in extremity	3/39 (7.7%)
Arthralgia	6/39 (15.4%)
Nervous system disorders
Headache	15/39 (38.5%)
Dizziness	4/39 (10.3%)
Paraesthesia	3/39 (7.7%)
Psychiatric disorders
Depression	3/39 (7.7%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	2/39 (5.1%)
Pleural effusion	10/39 (25.6%)
Dyspnoea	10/39 (25.6%)
Cough	6/39 (15.4%)
Pulmonary hypertension	2/39 (5.1%)
Rhinitis allergic	2/39 (5.1%)
Skin and subcutaneous tissue disorders
Pruritus	4/39 (10.3%)
Rash	10/39 (25.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.