Trial Outcomes & Findings for A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia (NCT NCT00481247)

NCT ID: NCT00481247

Last Updated: 2017-02-15

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

547 participants

Primary outcome timeframe

Pretreatment, every 3 months up to 12 months

Results posted on

2017-02-15

Participant Flow

Of the 547 patients enrolled, 519 were randomized and 516 received treatment. Of the 28 who were enrolled but not randomized, 20 no longer met study criteria, 3 withdrew consent, 1 was lost to follow-up, and 4 withdrew for other reasons.

Participant milestones

Participant milestones
Measure	Dasatinib Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib Tablets, oral, imatinib 400mg once daily (QD)
Overall Study STARTED	259	260
Overall Study Received Treatment	258	258
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	259	260

Reasons for withdrawal

Reasons for withdrawal
Measure	Dasatinib Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib Tablets, oral, imatinib 400mg once daily (QD)
Overall Study Death	0	1
Overall Study Disease progression	18	22
Overall Study Intolerance	42	17
Overall Study Treatment failure	10	14
Overall Study AE unrelated to study drug	13	4
Overall Study Withdrawal by Subject	8	13
Overall Study Pregnancy	2	1
Overall Study Lost to Follow-up	1	2
Overall Study Poor compliance/noncompliance	1	7
Overall Study Administrative reason by sponsor	157	162
Overall Study Varied	6	15
Overall Study Did not receive treatment	1	2

Baseline Characteristics

A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dasatinib n=259 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=260 Participants Tablets, oral, imatinib 400 mg once daily (QD)	Total n=519 Participants Total of all reporting groups
Age, Continuous	46.4 Years STANDARD_DEVIATION 14.6 • n=5 Participants	47.1 Years STANDARD_DEVIATION 13.9 • n=7 Participants	46.7 Years STANDARD_DEVIATION 14.2 • n=5 Participants
Age, Customized <20 years	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Age, Customized Between 21 and 45 years	123 Participants n=5 Participants	102 Participants n=7 Participants	225 Participants n=5 Participants
Age, Customized Between 46 and 65 years	111 Participants n=5 Participants	125 Participants n=7 Participants	236 Participants n=5 Participants
Age, Customized Between 66 and 75 years	13 Participants n=5 Participants	20 Participants n=7 Participants	33 Participants n=5 Participants
Age, Customized >75 years	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Gender Female	115 Participants n=5 Participants	97 Participants n=7 Participants	212 Participants n=5 Participants
Gender Male	144 Participants n=5 Participants	163 Participants n=7 Participants	307 Participants n=5 Participants
Race/Ethnicity, Customized White	132 Participants n=5 Participants	143 Participants n=7 Participants	275 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	108 Participants n=5 Participants	95 Participants n=7 Participants	203 Participants n=5 Participants
Race/Ethnicity, Customized Other	17 Participants n=5 Participants	21 Participants n=7 Participants	38 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG score=0	213 Participants n=5 Participants	205 Participants n=7 Participants	418 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG score=1	46 Participants n=5 Participants	53 Participants n=7 Participants	99 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG score=2	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Number of Patients With Liver Involvement	37 Participants n=5 Participants	18 Participants n=7 Participants	55 Participants n=5 Participants
Number of Participants With Spleen Involvement	83 Participants n=5 Participants	71 Participants n=7 Participants	154 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pretreatment, every 3 months up to 12 months

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Dasatinib n=259 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=260 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months	204 Participants	177 Participants

SECONDARY outcome

Timeframe: Years 2, 3, 4 and 5

Population: All randomized participants who achieved cCCyR

Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR. Percentage of participants in cCCyR at years 2, 3, 4 and 5 was computed for all randomized participants who achieved cCCyR as measured from the time of first confirmation until the date of progression or death. Participants with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Participants without cCCyR are considered to have progressed on Day 1.

Outcome measures

Outcome measures
Measure	Dasatinib n=215 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=204 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR) At Year 2	98.0 percentage of participants Interval 94.7 to 99.2	96.9 percentage of participants Interval 93.2 to 98.6
Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR) At Year 3	96.9 percentage of participants Interval 93.3 to 98.6	95.7 percentage of participants Interval 91.6 to 97.8
Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR) At Year 4	95.6 percentage of participants Interval 91.4 to 97.8	95.7 percentage of participants Interval 91.6 to 97.8
Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR) At Year 5	93.1 percentage of participants Interval 86.5 to 96.5	91.0 percentage of participants Interval 83.6 to 95.2

SECONDARY outcome

Timeframe: Planned total follow-up duration of 5 years

Population: All randomized participants

Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).

Outcome measures

Outcome measures
Measure	Dasatinib n=259 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=260 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Percentage of Participants With Major Molecular Response (MMR) at Any Time	76.4 Percentage of participants	64.2 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 to 5 years

Population: All randomized participants who achieved cCCyR

The time to cCCyR for all randomized participants is defined as the time from the randomization date until criteria are first met for complete cytogenic response (provided it is confirmed later). The time to cCCyR analysis censors nonresponders who do not progress at their last cytogenetic assessments and nonresponders who progress at the maximum time of all randomized participants. .

Outcome measures

Outcome measures
Measure	Dasatinib n=215 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=204 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Time to Confirmed Complete Cytogenic Response (cCCyR) Overall	3.1 Months Interval 3.0 to 3.1	5.8 Months Interval 5.6 to 6.0

SECONDARY outcome

Timeframe: Day 1 to 5 years

Population: All participants who received treatment and achieved MMR

The time to MMR for all randomized participants is defined as the time from randomization date until measurement criteria are first met for MMR. The time to MMR analysis censors nonresponders who do not progress at their last molecular assessments and nonresponders who progress at the maximum time of all randomized participants.

Outcome measures

Outcome measures
Measure	Dasatinib n=198 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=167 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Time to Major Molecular Response (MMR) Overall	9.3 Months Interval 8.8 to 11.8	15.0 Months Interval 12.2 to 18.2

SECONDARY outcome

Timeframe: Participants were followed-up for at least 5 years

Population: All randomized participants

PFS was defined as the time from randomization until progression (any progression/death within 30 days of last dosing date, or between 30-60 days of last dosing prior to start of secondary therapy). Those who did not progress/die or who progressed/died after 60 days of last dose were censored at last on-study hematologic/cytogenetic assessment; those with progression/death 30-60 days of last dosing date and after start date of secondary therapy censored at last on-study hematologic/cytogenetic assessment prior to start of secondary therapy; those who had not received study treatment censored on date randomized.

Outcome measures

Outcome measures
Measure	Dasatinib n=259 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=260 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Percentage of Participants With Progression-free Survival (PFS)	88.9 Percentage of participants	89.2 Percentage of participants

SECONDARY outcome

Timeframe: Participants were followed-up for at least 5 years

Population: All randomized participants

OS was defined as the time from randomization to the date of death. If the participant had not died, survival was censored on last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Dasatinib n=259 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=260 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Percentage of Participants With Overall Survival (OS)	90.9 Percentage of participants	89.6 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of last person, first visit to date of last person, last visit (approximately 8 years)

Population: All treated participants

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

Outcome measures

Outcome measures
Measure	Dasatinib n=258 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=258 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Muscle spasms	14 Participants	63 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths All AEs	251 Participants	251 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths All Drug-related AEs	224 Participants	231 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Diarrhea	100 Participants	91 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Pleural effusion	74 Participants	3 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Nausea	40 Participants	74 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Cough	68 Participants	28 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Thrombocytopenia	61 Participants	50 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Neutropenia	60 Participants	49 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Headache	59 Participants	46 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Pyrexia	58 Participants	51 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Vomiting	43 Participants	54 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths SAEs	90 Participants	70 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths Drug-related SAEs	43 Participants	22 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths AEs leading to discontinuation	51 Participants	26 Participants
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths All deaths	26 Participants	26 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From date of last person, first visit to date of last person, last visit (approximately 8 years)

Population: Participants with laboratory assessments

ULN=upper limit of normal. Grade 3=Severe AE; Grade 4=Life-threatening or disabling AE. Absolute neutrophil count: Grade 3 \<1000-500/mm\^3; Grade 4 \<500/mm\^3. Hemoglobin: Grade 3 \<8.0-6.5 g/dL; Grade 4 \<6.5 g/dL. Platelets: Grade 3 \<50,000-25,000/mm\^3; Grade 4 \<25,000/mm\^3. ALT/AST: Grade 3 \>5.0-20\*ULN; Grade 4 \>20\*ULN. Total bilirubin: Grade 3 \>3-10\*ULN; Grade 4 \>10\*ULN. Sample normal ranges (may vary by institution): ALT, Female: 7-30 U/L, Male: 10-55 U/L; AST, Female: 9-25 U/L, Male10-40 U/L; Total bilirubin: 0.0-1.0 mg/dL. Creatinine: Grade 3 \>3.0-6.0\*ULN; Grade 4 \>6.0\*ULN. Phosphate: Grade 3 \<2.0-1.0 mg/dL; Grade 4 \<1.0 mg/dL. Calcium: Grade 3 \<7.0-6.0 mg/dL; Grade 4 \<6.0 mg/dL. Potassium: Grade 3 \<3.0-2.5 mmol/L; Grade 4 \<2.5 mmol/L.

Outcome measures

Outcome measures
Measure	Dasatinib n=256 Participants Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=257 Participants Tablets, oral, imatinib 400 mg once daily (QD)
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Absolute neutrophil count	74 Participants	61 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Hemoglobin	35 Participants	23 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Platelets	56 Participants	37 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Alanine aminotransferase (ALT)	2 Participants	4 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Aspartate aminotransferase (AST)	2 Participants	3 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Total bilirubin	3 Participants	0 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Creatinine	3 Participants	2 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Phosphate	19 Participants	79 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Calcium	9 Participants	7 Participants
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results Grade 3/4 Potassium	0 Participants	8 Participants

Adverse Events

Dasatinib

Serious events: 90 serious events

Other events: 216 other events

Deaths: 0 deaths

Imatinib

Serious events: 70 serious events

Other events: 231 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Dasatinib n=258 participants at risk Tablets, oral, dasatinib 100 mg once daily (QD)	Imatinib n=258 participants at risk Tablets, oral, imatinib 400 mg once daily (QD)
Blood and lymphatic system disorders ANAEMIA	14.7% 38/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	12.0% 31/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Blood and lymphatic system disorders LEUKOPENIA	8.1% 21/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	10.9% 28/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Blood and lymphatic system disorders NEUTROPENIA	23.3% 60/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	19.0% 49/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Blood and lymphatic system disorders THROMBOCYTOPENIA	22.9% 59/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	18.6% 48/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Eye disorders EYELID OEDEMA	2.7% 7/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	15.5% 40/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Eye disorders PERIORBITAL OEDEMA	1.6% 4/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	7.8% 20/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders ABDOMINAL PAIN	14.0% 36/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	10.9% 28/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders ABDOMINAL PAIN UPPER	8.5% 22/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	7.0% 18/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders CONSTIPATION	8.1% 21/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	2.7% 7/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders DIARRHOEA	38.4% 99/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	34.5% 89/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders DYSPEPSIA	6.6% 17/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	8.5% 22/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders GASTRITIS	8.9% 23/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	7.0% 18/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders NAUSEA	15.5% 40/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	28.7% 74/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders VOMITING	15.9% 41/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	20.2% 52/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
General disorders ASTHENIA	16.3% 42/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	14.3% 37/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
General disorders CHEST PAIN	9.3% 24/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	5.0% 13/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
General disorders FACE OEDEMA	5.4% 14/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	10.5% 27/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
General disorders FATIGUE	15.5% 40/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	15.5% 40/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
General disorders INFLUENZA LIKE ILLNESS	8.9% 23/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	6.6% 17/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
General disorders OEDEMA	3.9% 10/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	9.3% 24/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
General disorders OEDEMA PERIPHERAL	9.7% 25/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	12.4% 32/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
General disorders PYREXIA	22.5% 58/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	19.4% 50/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Gastrointestinal disorders TOOTHACHE	6.6% 17/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	3.9% 10/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Infections and infestations NASOPHARYNGITIS	12.4% 32/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	16.7% 43/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	11.6% 30/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	10.9% 28/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Investigations HAEMOGLOBIN DECREASED	11.6% 30/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	6.6% 17/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Investigations WEIGHT INCREASED	9.7% 25/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	12.8% 33/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Infections and infestations BRONCHITIS	7.8% 20/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	5.4% 14/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Infections and infestations CONJUNCTIVITIS	3.9% 10/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	6.6% 17/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Infections and infestations GASTROENTERITIS	7.4% 19/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	3.9% 10/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Infections and infestations INFLUENZA	7.8% 20/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	4.7% 12/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Infections and infestations URINARY TRACT INFECTION	4.3% 11/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	5.0% 13/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Investigations ALANINE AMINOTRANSFERASE INCREASE	5.0% 13/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	2.7% 7/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Metabolism and nutrition disorders DECREASED APPETITE	8.9% 23/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	5.0% 13/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Musculoskeletal and connective tissue disorders ARTHRALGIA	13.2% 34/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	14.7% 38/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Musculoskeletal and connective tissue disorders BACK PAIN	13.2% 34/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	17.1% 44/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	5.4% 14/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	24.4% 63/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	8.5% 22/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	7.4% 19/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Musculoskeletal and connective tissue disorders MYALGIA	14.0% 36/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	15.1% 39/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	10.9% 28/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	15.1% 39/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Nervous system disorders DIZZINESS	10.9% 28/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	7.0% 18/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Nervous system disorders HEADACHE	22.9% 59/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	17.8% 46/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Psychiatric disorders INSOMNIA	7.8% 20/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	6.2% 16/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Psychiatric disorders DEPRESSION	1.9% 5/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	5.0% 13/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Respiratory, thoracic and mediastinal disorders COUGH	26.4% 68/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	10.9% 28/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Respiratory, thoracic and mediastinal disorders DYSPNOEA	14.0% 36/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	3.9% 10/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	26.7% 69/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	1.2% 3/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	5.4% 14/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	4.3% 11/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Skin and subcutaneous tissue disorders PRURITUS	5.8% 15/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	7.4% 19/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Skin and subcutaneous tissue disorders RASH	17.4% 45/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	17.1% 44/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Skin and subcutaneous tissue disorders ACNE	5.4% 14/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	0.39% 1/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Vascular disorders PALLOR	2.7% 7/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	5.0% 13/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015
Vascular disorders HYPERTENSION	10.1% 26/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015	7.8% 20/258 • Randomization to end of study (December 2015) Study initiated: September 2007; End of Study: December 2015