Study of Dasatinib in Patients With Chronic Phase Chronic Myeloid Leukemia and a Suboptimal Response to Imatinib

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00320190
• Collaborator: (none)
• Enrollment: 52
• Locations: 27
• Arms: 2
• Duration (Months): 41
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of dasatinib with that of high-dose (800-mg) imatinib in participants with chronic phase chronic myeloid leukemia who achieved only a suboptimal response after at least 3 months of monotherapy with 400-mg imatinib. The safety of these treatments will also be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Chronic	Drug: Imatinib; Drug: Dasatinib	Phase 2

Detailed Description

Participants were randomized 2:1 to dasatinib or high-dose imatinib, respectively. Randomization was stratified by a suboptimal response, defined as a hematologic response less than a complete hematologic response after at least 3 months of monotherapy with 400-mg imatinib; a cytogenic response (CgR) less than a partial CgR (PCgR) after at least 6 months of monotherapy with 400-mg; a PCgR after at least 12 months of monotherapy with 400-mg imatinib; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with 400-mg imatinib.

Participants received either dasatinib or imatinib for 12 months or until disease progression, unacceptable toxicity, consent withdrawal, or study discontinuation. After 12 months, who had a confirmed major molecular response and were still receiving dasatinib, 100 mg, or imatinib, 800 mg, were eligible to extend treatment for an additional 12 months. Participants permanently discontinuing treatment before 12 months were considered treatment failures and withdrawn from the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized Study of Dasatinib vs High-dose (800-mg) Imatinib in the Treatment of Subjects With Chronic Phase Chronic Myeloid Leukemia Who Have Had a Suboptimal Response After at Least 3 Months of Therapy With 400 mg Imatinib
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dasatinib Participants with chronic phase chronic myeloid leukemia (CML) who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg.	Drug: Dasatinib; Dasatinib tablets administered orally at a dose of 100 mg once daily.
Active Comparator: Imatinib Participants with chronic phase CML who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg.	Drug: Imatinib; Imatinib tablets administered orally at a dose of 400 mg twice daily. Each 400- mg dose to be taken with a meal and a large glass of water.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR) [At 12 months from baseline]

   MMolR is defined as reduction in transcript levels of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene of at least 3 log. The BCR-ABL gene has a role in the production of a mutated protein that converts bone marrow stem cells from normal to leukemic.

Secondary Outcome Measures

1. Percentage of Participants With Death as Outcome, Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, and AEs Leading to Discontinuation [Months 1 to 12, continuously, and Months 12 to 24, continuously]

   AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical occurrence that at any dose results in death, persistent or significant disability/incapacity, drug dependency, or drug abuse; prolongs inpatient hospitalization; or is life-threatening, a congenital anomaly/birth defect, or an important medical event. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.

2. Percentage of Participants With On-study AEs of Special Interest [Months 1 to 12, continuously, and Months 12 to 24, continuously]

   GI=gastrointestinal. AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. Grade 1=mild; Grade 2=moderate; Grade 3=severe and undesirable; Grade 4=life-threatening or disabling; Grade 5=death. Percentages based on the number of participants with a specific grade at baseline. Participants without on-study test values for a particular laboratory analyte are not included in the reporting of that analyte.

3. Median Time to MMolR [At 3, 6, 9, and 12 months from baseline]

   Time to MMolR is defined as the time from first treatment dose until measurement criteria are first met for MMolR. MMolR is defined as a reduction in transcript levels of the BCR-ABL gene of at least 3 log from baseline.

4. Percentage of Participants With Complete Cytogenetic Response [At 6 and 12 months from baseline]

   Cytogenetic response is based on the prevalence of Ph+ metaphases among cells in metaphase in a bone marrow sample.

5. Median Time to Treatment Failure [Randomization to disease progression, death, or discontinuation (to 12 months)]

   Time to treatment failure is defined as the time in days from randomization to progressive disease documented by the investigator, to death from any cause without prior progression, or to early treatment discontinuation for any reason, whichever occurs first. Participants without disease progression or who do not die and complete the 12-month study treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.

6. Median Time to Progression-free Survival [Randomization to disease progression or death (to 12 months)]

   Progression-free survival is defined as the time in days from randomization to progressive disease documented by the investigator or to death from any cause without prior progression. Participants without progressive disease or who do not die and complete the 12-month treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Chronic phase Ph^+ chronic myeloid leukemia (CML) demonstrating only a suboptimal response, defined as a hematologic response that is less than a complete hematologic response after at least 3 months of monotherapy with imatinib, 400 mg; a cytogenic response (CgR) that is less than a partial CgR (PCgR) after at least 6 months of monotherapy with imatinib, 400 mg; a PCgR after at least 12 months of monotherapy with imatinib, 400 mg; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with imatinib, 400 mg.

• Either gender

• Age of 18 years or older

Exclusion Criteria:

• Previous diagnosis of accelerated phase or blast crisis CML

• Uncontrolled or significant cardiovascular disease

• History of significant bleeding disorder unrelated to CML

• Concurrent malignancies

• Intolerance of imatinib, 400 mg

• Prior treatment with imatinib at a dose higher than 400 mg

• Prior stem cell transplantation and/or high-dose chemotherapy for CML

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Antwerpen		Belgium	2060
2	Local Institution	Charleroi		Belgium	6000
3	Local Institution	Helsinki		Finland	00029
4	Local Institution	Tampere		Finland	33380
5	Local Institution	Lyon Cedex 03		France	69437
6	Local Institution	Marseille Cedex 9		France	13273
7	Local Institution	Montpellier Cedex 5		France	34295
8	Local Institution	Paris Cedex 10		France	75475
9	Local Institution	Rennes		France	35033
10	Local Institution	Strasbourg Cedex		France	67091
11	Local Institution	Toulouse Cedex 09		France	31059
12	Local Institution	Leipzig		Germany	04103
13	Local Institution	Orbassano (To)		Italy	10043
14	Local Institution	Oslo		Norway	0027
15	Local Institution	Trondheim		Norway	7006
16	Local Institution	Lisboa		Portugal	1649-035
17	Local Institution	Moscow		Russian Federation	125167
18	Local Institution	Saint-Petersburg		Russian Federation	191024
19	Local Institution	St.Petersburg		Russian Federation	197022
20	Local Institution	Murcia		Spain	30008
21	Local Institution	Lund		Sweden	221 85
22	Local Institution	Orebro		Sweden	70185
23	Local Institution	Uppsala		Sweden	751 85
24	Local Institution	Glasgow	Central	United Kingdom	G31 2ER
25	Local Institution	London	Greater London	United Kingdom	SE5 9RS
26	Local Institution	London	Greater London	United Kingdom	W12 ONN
27	Local Institution	Leeds	North Yorkshire	United Kingdom	LS9 7FT

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00320190
• Other Study ID Numbers: CA180-043; EUDRACT Number: 2005-005153-22
• First Posted: May 3, 2006
• Last Update Posted: Oct 30, 2013
• Last Verified: Jul 1, 2011

• Keywords provided by Bristol-Myers Squibb: Chronic phase CML, with a suboptimal response after treatment with imatinib
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Imatinib Mesylate; Dasatinib

Study Results

Participant Flow

Pre-assignment Detail	Of 52 participants enrolled, 32 were randomized to treatment. Of the 20 not randomized, 17 no longer met study criteria, 1 participant had an adverse event prior to randomization, 1 participant was enrolled after the sponsor stopped recruitment, and 1 participant was stopped due to administrative reasons.

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.
Period Title: First 12 Months
STARTED	19	13
COMPLETED	11	3
NOT COMPLETED	8	10
Period Title: First 12 Months
STARTED	11	3
COMPLETED	2	1
NOT COMPLETED	9	2

Baseline Characteristics

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg	Total
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.	Total of all reporting groups
Overall Participants	19	13	32
Age, Customized (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	45.5 (14.83)	53.2 (14.24)	48.6 (14.85)
Sex: Female, Male (Count of Participants)
Female	6 31.6%	3 23.1%	9 28.1%
Male	13 68.4%	10 76.9%	23 71.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 5.3%	0 0%	1 3.1%
White	18 94.7%	13 100%	31 96.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR)
Description	MMolR is defined as reduction in transcript levels of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene of at least 3 log. The BCR-ABL gene has a role in the production of a mutated protein that converts bone marrow stem cells from normal to leukemic.
Time Frame	At 12 months from baseline

Outcome Measure Data

Analysis Population Description

Efficacy analyses as originally described in the protocol were not conducted because of the low number of participants enrolled.

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.
Measure Participants	0	0

2. Secondary Outcome

Title	Percentage of Participants With Death as Outcome, Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, and AEs Leading to Discontinuation
Description	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical occurrence that at any dose results in death, persistent or significant disability/incapacity, drug dependency, or drug abuse; prolongs inpatient hospitalization; or is life-threatening, a congenital anomaly/birth defect, or an important medical event. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Time Frame	Months 1 to 12, continuously, and Months 12 to 24, continuously

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of dasatinib or imatinib.

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.
Measure Participants	19	13
Deaths	0 0%	0 0%
AEs	94.7 498.4%	92.3 710%
Treatment-related AEs	78.9 415.3%	92.3 710%
SAEs	15.8 83.2%	7.7 59.2%
Treatment-related SAEs	5.3 27.9%	7.7 59.2%
AEs leading to discontinuation	5.3 27.9%	7.7 59.2%

3. Secondary Outcome

Title	Percentage of Participants With On-study AEs of Special Interest
Description	GI=gastrointestinal. AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. Grade 1=mild; Grade 2=moderate; Grade 3=severe and undesirable; Grade 4=life-threatening or disabling; Grade 5=death. Percentages based on the number of participants with a specific grade at baseline. Participants without on-study test values for a particular laboratory analyte are not included in the reporting of that analyte.
Time Frame	Months 1 to 12, continuously, and Months 12 to 24, continuously

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of dasatinib or imatinib.

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.
Measure Participants	19	13
Fluid retention (Any grade)	5.3 27.9%	38.5 296.2%
Fluid retention (Grades 3-5)	0 0%	7.7 59.2%
Fluid retention: Superficial edema (Any grade)	0 0%	30.8 236.9%
Fluid retention: Superficial edema (Grades 3-5)	0 0%	0 0%
Fluid retention: Generalized edema (Any grade)	5.3 27.9%	7.7 59.2%
Fluid retention: Generalized edema (Grades 3-5)	0 0%	7.7 59.2%
Hemorrhage (Any grade)	0 0%	15.4 118.5%
Hemorrhage (Grades 3-5)	0 0%	0 0%
Hemorrhage: GI bleeding (Any grade)	0 0%	7.7 59.2%
Hemorrhage: GI bleeding (Grades 3-5)	0 0%	0 0%
Hemorrhage: Other bleeding (Any grade)	0 0%	7.7 59.2%
Hemorrhage: Other bleeding (Grades 3-5)	0 0%	0 0%
Diarrhea (Any grade)	26.3 138.4%	30.8 236.9%
Diarrhea (Grades 3-5)	0 0%	0 0%
Skin rash (Any grade)	42.1 221.6%	15.4 118.5%
Skin rash (Grades 3-5)	0 0%	0 0%

4. Secondary Outcome

Title	Median Time to MMolR
Description	Time to MMolR is defined as the time from first treatment dose until measurement criteria are first met for MMolR. MMolR is defined as a reduction in transcript levels of the BCR-ABL gene of at least 3 log from baseline.
Time Frame	At 3, 6, 9, and 12 months from baseline

Outcome Measure Data

Analysis Population Description

Efficacy analyses as originally described in the protocol were not conducted because of the low number of participants enrolled.

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.
Measure Participants	0	0

5. Secondary Outcome

Title	Percentage of Participants With Complete Cytogenetic Response
Description	Cytogenetic response is based on the prevalence of Ph+ metaphases among cells in metaphase in a bone marrow sample.
Time Frame	At 6 and 12 months from baseline

Outcome Measure Data

Analysis Population Description

Efficacy analyses as originally described in the protocol were not conducted because of the low number of participants enrolled.

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.
Measure Participants	0	0

6. Secondary Outcome

Title	Median Time to Treatment Failure
Description	Time to treatment failure is defined as the time in days from randomization to progressive disease documented by the investigator, to death from any cause without prior progression, or to early treatment discontinuation for any reason, whichever occurs first. Participants without disease progression or who do not die and complete the 12-month study treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.
Time Frame	Randomization to disease progression, death, or discontinuation (to 12 months)

Outcome Measure Data

Analysis Population Description

Efficacy analyses as originally described in the protocol were not conducted because of the low number of participants enrolled.

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.
Measure Participants	0	0

7. Secondary Outcome

Title	Median Time to Progression-free Survival
Description	Progression-free survival is defined as the time in days from randomization to progressive disease documented by the investigator or to death from any cause without prior progression. Participants without progressive disease or who do not die and complete the 12-month treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.
Time Frame	Randomization to disease progression or death (to 12 months)

Outcome Measure Data

Analysis Population Description

Efficacy analyses as originally described in the protocol were not conducted because of the low number of participants enrolled.

Arm/Group Title	Dasatinib, 100 mg	Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.	Imatinib, 400 mg, administered orally twice daily.
Measure Participants	0	0

Adverse Events

Time Frame	Baseline to Month 12 and Month 12 to Month 24
Arm/Group Title	Dasatinib, 100 mg		Imatinib, 800 mg
Arm/Group Description	Dasatinib, 100 mg, administered orally once daily.		Imatinib, 400 mg, administered orally twice daily
All Cause Mortality
	Dasatinib, 100 mg		Imatinib, 800 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dasatinib, 100 mg		Imatinib, 800 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)		1/13 (7.7%)
Gastrointestinal disorders
MELAENA	0/19 (0%)		1/13 (7.7%)
HAEMATEMESIS	0/19 (0%)		1/13 (7.7%)
Infections and infestations
PNEUMONIA	1/19 (5.3%)		0/13 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER	1/19 (5.3%)		0/13 (0%)
Skin and subcutaneous tissue disorders
SKIN BURNING SENSATION	1/19 (5.3%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Dasatinib, 100 mg		Imatinib, 800 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/19 (94.7%)		12/13 (92.3%)
Blood and lymphatic system disorders
LYMPHOCYTOSIS	2/19 (10.5%)		0/13 (0%)
THROMBOCYTOPENIA	2/19 (10.5%)		0/13 (0%)
IRON DEFICIENCY ANAEMIA	1/19 (5.3%)		0/13 (0%)
Cardiac disorders
ANGINA PECTORIS	0/19 (0%)		1/13 (7.7%)
Ear and labyrinth disorders
VERTIGO	0/19 (0%)		1/13 (7.7%)
EAR PAIN	0/19 (0%)		1/13 (7.7%)
TINNITUS	2/19 (10.5%)		0/13 (0%)
Endocrine disorders
GOITRE	0/19 (0%)		1/13 (7.7%)
Eye disorders
EYE PAIN	1/19 (5.3%)		0/13 (0%)
EYE SWELLING	0/19 (0%)		1/13 (7.7%)
EYE DISCHARGE	1/19 (5.3%)		0/13 (0%)
EYELID OEDEMA	0/19 (0%)		1/13 (7.7%)
CONJUNCTIVITIS	0/19 (0%)		2/13 (15.4%)
EYE IRRITATION	0/19 (0%)		1/13 (7.7%)
ORBITAL OEDEMA	0/19 (0%)		1/13 (7.7%)
OCULAR HYPERAEMIA	0/19 (0%)		1/13 (7.7%)
LACRIMATION INCREASED	0/19 (0%)		2/13 (15.4%)
DACRYOSTENOSIS ACQUIRED	1/19 (5.3%)		0/13 (0%)
Gastrointestinal disorders
NAUSEA	2/19 (10.5%)		7/13 (53.8%)
VOMITING	3/19 (15.8%)		5/13 (38.5%)
DIARRHOEA	5/19 (26.3%)		4/13 (30.8%)
DYSPEPSIA	1/19 (5.3%)		1/13 (7.7%)
TOOTHACHE	0/19 (0%)		1/13 (7.7%)
FLATULENCE	3/19 (15.8%)		0/13 (0%)
LIP BLISTER	1/19 (5.3%)		0/13 (0%)
CONSTIPATION	2/19 (10.5%)		0/13 (0%)
DENTAL CARIES	1/19 (5.3%)		0/13 (0%)
ABDOMINAL PAIN	1/19 (5.3%)		0/13 (0%)
TOOTH DISORDER	1/19 (5.3%)		0/13 (0%)
ABDOMINAL DISCOMFORT	1/19 (5.3%)		0/13 (0%)
ABDOMINAL DISTENSION	3/19 (15.8%)		0/13 (0%)
ABDOMINAL PAIN UPPER	1/19 (5.3%)		0/13 (0%)
MALLORY-WEISS SYNDROME	0/19 (0%)		1/13 (7.7%)
GASTROINTESTINAL DISORDER	0/19 (0%)		1/13 (7.7%)
GASTROOESOPHAGEAL SPHINCTER INSUFFICIENCY	0/19 (0%)		1/13 (7.7%)
General disorders
CHILLS	1/19 (5.3%)		0/13 (0%)
OEDEMA	0/19 (0%)		1/13 (7.7%)
FATIGUE	7/19 (36.8%)		3/13 (23.1%)
MALAISE	1/19 (5.3%)		0/13 (0%)
PYREXIA	5/19 (26.3%)		0/13 (0%)
ASTHENIA	1/19 (5.3%)		3/13 (23.1%)
CHEST PAIN	1/19 (5.3%)		1/13 (7.7%)
FACIAL PAIN	0/19 (0%)		1/13 (7.7%)
AXILLARY PAIN	2/19 (10.5%)		0/13 (0%)
INFLUENZA LIKE ILLNESS	3/19 (15.8%)		0/13 (0%)
Immune system disorders
SEASONAL ALLERGY	1/19 (5.3%)		0/13 (0%)
Infections and infestations
INFECTION	0/19 (0%)		1/13 (7.7%)
INFLUENZA	1/19 (5.3%)		0/13 (0%)
SINUSITIS	1/19 (5.3%)		1/13 (7.7%)
BRONCHITIS	1/19 (5.3%)		0/13 (0%)
PHARYNGITIS	0/19 (0%)		1/13 (7.7%)
TONSILLITIS	1/19 (5.3%)		0/13 (0%)
EAR INFECTION	0/19 (0%)		1/13 (7.7%)
LABYRINTHITIS	1/19 (5.3%)		0/13 (0%)
ONYCHOMYCOSIS	1/19 (5.3%)		1/13 (7.7%)
GASTROENTERITIS	1/19 (5.3%)		1/13 (7.7%)
NASOPHARYNGITIS	2/19 (10.5%)		2/13 (15.4%)
TOOTH INFECTION	1/19 (5.3%)		0/13 (0%)
ORAL CANDIDIASIS	0/19 (0%)		1/13 (7.7%)
LOCALISED INFECTION	1/19 (5.3%)		0/13 (0%)
FUNGAL SKIN INFECTION	1/19 (5.3%)		0/13 (0%)
GASTROENTERITIS VIRAL	1/19 (5.3%)		1/13 (7.7%)
HERPES VIRUS INFECTION	0/19 (0%)		1/13 (7.7%)
UPPER RESPIRATORY TRACT INFECTION	1/19 (5.3%)		0/13 (0%)
Injury, poisoning and procedural complications
THERMAL BURN	1/19 (5.3%)		0/13 (0%)
Investigations
BIOPSY	1/19 (5.3%)		0/13 (0%)
CARDIAC MURMUR	1/19 (5.3%)		0/13 (0%)
WEIGHT DECREASED	1/19 (5.3%)		0/13 (0%)
BLOOD CALCIUM INCREASED	1/19 (5.3%)		0/13 (0%)
BLOOD PHOSPHORUS DECREASED	0/19 (0%)		1/13 (7.7%)
BLOOD PHOSPHORUS INCREASED	1/19 (5.3%)		0/13 (0%)
ELECTROCARDIOGRAM QT INTERVAL	0/19 (0%)		1/13 (7.7%)
ALANINE AMINOTRANSFERASE INCREASED	2/19 (10.5%)		0/13 (0%)
ASPARTATE AMINOTRANSFERASE INCREASED	2/19 (10.5%)		0/13 (0%)
BLOOD ALKALINE PHOSPHATASE INCREASED	1/19 (5.3%)		0/13 (0%)
BLOOD LACTATE DEHYDROGENASE INCREASED	1/19 (5.3%)		0/13 (0%)
Metabolism and nutrition disorders
GOUT	1/19 (5.3%)		0/13 (0%)
HYPOKALAEMIA	1/19 (5.3%)		0/13 (0%)
FLUID RETENTION	1/19 (5.3%)		0/13 (0%)
DECREASED APPETITE	1/19 (5.3%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
MYALGIA	3/19 (15.8%)		2/13 (15.4%)
BACK PAIN	4/19 (21.1%)		0/13 (0%)
ARTHRALGIA	2/19 (10.5%)		0/13 (0%)
MUSCLE SPASMS	1/19 (5.3%)		3/13 (23.1%)
PAIN IN EXTREMITY	2/19 (10.5%)		0/13 (0%)
MUSCULOSKELETAL PAIN	0/19 (0%)		1/13 (7.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MELANOCYTIC NAEVUS	1/19 (5.3%)		0/13 (0%)
Nervous system disorders
HEADACHE	8/19 (42.1%)		4/13 (30.8%)
MIGRAINE	0/19 (0%)		1/13 (7.7%)
DIZZINESS	1/19 (5.3%)		0/13 (0%)
DYSGEUSIA	0/19 (0%)		1/13 (7.7%)
FACIAL PALSY	0/19 (0%)		1/13 (7.7%)
FACIAL NEURALGIA	0/19 (0%)		1/13 (7.7%)
DISTURBANCE IN ATTENTION	0/19 (0%)		1/13 (7.7%)
Psychiatric disorders
ANXIETY	0/19 (0%)		1/13 (7.7%)
INSOMNIA	1/19 (5.3%)		1/13 (7.7%)
AGGRESSION	2/19 (10.5%)		0/13 (0%)
DEPRESSED MOOD	0/19 (0%)		1/13 (7.7%)
Renal and urinary disorders
DYSURIA	0/19 (0%)		1/13 (7.7%)
NOCTURIA	1/19 (5.3%)		0/13 (0%)
HAEMATURIA	0/19 (0%)		1/13 (7.7%)
PROTEINURIA	1/19 (5.3%)		0/13 (0%)
Reproductive system and breast disorders
BREAST MASS	1/19 (5.3%)		0/13 (0%)
EPIDIDYMAL CYST	1/19 (5.3%)		0/13 (0%)
TESTICULAR PAIN	1/19 (5.3%)		0/13 (0%)
PRURITUS GENITAL	1/19 (5.3%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	3/19 (15.8%)		1/13 (7.7%)
DYSPNOEA	1/19 (5.3%)		1/13 (7.7%)
DYSPHONIA	1/19 (5.3%)		1/13 (7.7%)
ORTHOPNOEA	0/19 (0%)		1/13 (7.7%)
RHINORRHOEA	1/19 (5.3%)		1/13 (7.7%)
OROPHARYNGEAL PAIN	0/19 (0%)		2/13 (15.4%)
SPUTUM DISCOLOURED	0/19 (0%)		2/13 (15.4%)
INCREASED BRONCHIAL SECRETION	1/19 (5.3%)		0/13 (0%)
Skin and subcutaneous tissue disorders
RASH	6/19 (31.6%)		2/13 (15.4%)
ECZEMA	2/19 (10.5%)		0/13 (0%)
DRY SKIN	1/19 (5.3%)		1/13 (7.7%)
PRURITUS	2/19 (10.5%)		0/13 (0%)
URTICARIA	1/19 (5.3%)		0/13 (0%)
SKIN ULCER	1/19 (5.3%)		0/13 (0%)
RASH MACULAR	1/19 (5.3%)		0/13 (0%)
RASH PAPULAR	1/19 (5.3%)		0/13 (0%)
HYPERHIDROSIS	1/19 (5.3%)		0/13 (0%)
RASH ERYTHEMATOUS	0/19 (0%)		1/13 (7.7%)
PERIORBITAL OEDEMA	0/19 (0%)		2/13 (15.4%)
DERMATITIS ACNEIFORM	2/19 (10.5%)		0/13 (0%)
SKIN BURNING SENSATION	1/19 (5.3%)		0/13 (0%)
Vascular disorders
FLUSHING	0/19 (0%)		1/13 (7.7%)
HYPERTENSION	2/19 (10.5%)		0/13 (0%)
VENOUS INSUFFICIENCY	1/19 (5.3%)		0/13 (0%)

Limitations/Caveats

Enrollment terminated prematurely on September 5, 2008, due to slow accrual. Only 32 of 156 planned participants were randomized from August 2, 2006. Per BMS standards, findings were reported in a synopsis format, with only safety results included.

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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