Trial Outcomes & Findings for Docetaxel and Oxaliplatin in Gastric Cancer (NCT NCT00382720)

Last Updated: 2013-01-07

Results Overview

The number of months measured from the day of randomization to the first tumor progression according to World Health Organization (WHO) criteria evaluation of cancer response, or death from any cause. WHO Criteria for Progressive Disease: ≥ 25% increase in the size of at least one bidimensionally or unidimensionally measurable lesion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

275 participants

Primary outcome timeframe

every 8 weeks up to a maximum of 36 months

Results posted on

2013-01-07

Participant Flow

A total 275 participants from 12 countries were randomized in the part I/II study. 64 participants were enrolled in Part I. 211 new participants were enrolled specifically for Part II.

The intent-to-treat (ITT) population, included 254 participants randomized to the optimal dose of study medication from Parts I (43) and II (211), and excluded 21 participants administered the non-optimal dose in Part I.

Participant milestones

Participant milestones
Measure	(TE) Taxotere and Eloxatin Participants administered Docetaxel (Taxotere) 75 mg/m² as an 1-hour IV infusion on day 1 followed by Oxaliplatin (Eloxatin) 130 mg/m² as a two to six-hour IV infusion on day 1 per chemotherapy cycle.	(TEF) Taxotere, Eloxatin and 5-fluorouracil Participants administed with Docetaxel (Taxotere) 50 mg/m² as a 1-hour IV infusion day 1; Oxaliplatin (Eloxatin) 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion day 1 per chemotherapy cycle.	(TEX) Taxotere, Eloxatin and Xeloda Participants administered Docetaxel (Taxotere) 50 mg/m² as a 1-hour intravenous (IV) infusion on day 1, Oxaliplatin (Eloxatin) 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine (Xeloda) 625 mg/m2 two times a day continuously per chemotherapy cycle.
Overall Study STARTED	79	89	86
Overall Study Administered Non-Optimal Dose (Part I)	10	11	0
Overall Study Administered Optimal Dose (Parts I & II)	78	88	82
Overall Study Full Analysis Population (FAP)	78	88	82
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	79	89	86

Reasons for withdrawal

Reasons for withdrawal
Measure	(TE) Taxotere and Eloxatin Participants administered Docetaxel (Taxotere) 75 mg/m² as an 1-hour IV infusion on day 1 followed by Oxaliplatin (Eloxatin) 130 mg/m² as a two to six-hour IV infusion on day 1 per chemotherapy cycle.	(TEF) Taxotere, Eloxatin and 5-fluorouracil Participants administed with Docetaxel (Taxotere) 50 mg/m² as a 1-hour IV infusion day 1; Oxaliplatin (Eloxatin) 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion day 1 per chemotherapy cycle.	(TEX) Taxotere, Eloxatin and Xeloda Participants administered Docetaxel (Taxotere) 50 mg/m² as a 1-hour intravenous (IV) infusion on day 1, Oxaliplatin (Eloxatin) 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine (Xeloda) 625 mg/m2 two times a day continuously per chemotherapy cycle.
Overall Study Adverse Event	21	23	15
Overall Study Protocol Violation	2	5	1
Overall Study Death	0	1	2
Overall Study Progressive disease	37	28	38
Overall Study Withdrew consent	1	1	2
Overall Study Withdrawal by Subject	11	20	12
Overall Study Surgery	1	1	4
Overall Study Patient did not receive study medication	1	1	4
Overall Study Clinically progressive disease	0	1	0
Overall Study Good prognosis	0	1	0
Overall Study Investigator/Clinical decision	5	6	6
Overall Study Discontinued at end of study	0	1	2

Baseline Characteristics

Docetaxel and Oxaliplatin in Gastric Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	(TE) Taxotere and Eloxatin n=79 Participants Participants administered Docetaxel (Taxotere) 75 mg/m² as an 1-hour IV infusion on day 1 followed by Oxaliplatin (Eloxatin) 130 mg/m² as a two to six-hour IV infusion on day 1 per chemotherapy cycle.	(TEF) Taxotere, Eloxatin and 5-fluorouracil n=89 Participants Participants administed with Docetaxel (Taxotere) 50 mg/m² as a 1-hour IV infusion day 1; Oxaliplatin (Eloxatin) 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion day 1 per chemotherapy cycle.	(TEX) Taxotere, Eloxatin and Xeloda n=86 Participants Participants administered Docetaxel (Taxotere) 50 mg/m² as a 1-hour intravenous (IV) infusion on day 1, Oxaliplatin (Eloxatin) 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine (Xeloda) 625 mg/m2 two times a day continuously per chemotherapy cycle.	Total n=254 Participants Total of all reporting groups
Age Continuous	59.2 years STANDARD_DEVIATION 11.4 • n=93 Participants	57.9 years STANDARD_DEVIATION 11.1 • n=4 Participants	59.0 years STANDARD_DEVIATION 11.0 • n=27 Participants	58.7 years STANDARD_DEVIATION 11.1 • n=483 Participants
Sex: Female, Male Female	28 Participants n=93 Participants	28 Participants n=4 Participants	22 Participants n=27 Participants	78 Participants n=483 Participants
Sex: Female, Male Male	51 Participants n=93 Participants	61 Participants n=4 Participants	64 Participants n=27 Participants	176 Participants n=483 Participants
Race/Ethnicity, Customized Asian/Oriental	0 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Race/Ethnicity, Customized Black	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Race/Ethnicity, Customized White	77 participants n=93 Participants	87 participants n=4 Participants	84 participants n=27 Participants	248 participants n=483 Participants
Race/Ethnicity, Customized Unknown or Not Reported	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants	4 participants n=483 Participants
Karnofsky Performance Status (KPS) 100% Normal, no complaints: no evidence of disease	19 participants n=93 Participants	28 participants n=4 Participants	19 participants n=27 Participants	66 participants n=483 Participants
Karnofsky Performance Status (KPS) 90% Able to carry on normal activity; minor signs	26 participants n=93 Participants	35 participants n=4 Participants	31 participants n=27 Participants	92 participants n=483 Participants
Karnofsky Performance Status (KPS) 80% Normal activity with effort, some signs	31 participants n=93 Participants	24 participants n=4 Participants	33 participants n=27 Participants	88 participants n=483 Participants
Karnofsky Performance Status (KPS) 70% Cares for self but unable to work	1 participants n=93 Participants	2 participants n=4 Participants	3 participants n=27 Participants	6 participants n=483 Participants
Karnofsky Performance Status (KPS) <70% Requires assistance	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Karnofsky Performance Status (KPS) Missing	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Weight loss during last 3 months less than or equal to 5%	39 participants n=93 Participants	47 participants n=4 Participants	44 participants n=27 Participants	130 participants n=483 Participants
Weight loss during last 3 months greater than 5%	39 participants n=93 Participants	42 participants n=4 Participants	41 participants n=27 Participants	122 participants n=483 Participants
Weight loss during last 3 months Missing	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	2 participants n=483 Participants

PRIMARY outcome

Timeframe: every 8 weeks up to a maximum of 36 months

Population: 248 participants in the full analysis population (FAP).

Outcome measures

Outcome measures
Measure	(TE) Taxotere and Eloxatin n=78 Participants Participants administered Docetaxel (Taxotere) 75 mg/m² as an 1-hour IV infusion on day 1 followed by Oxaliplatin (Eloxatin) 130 mg/m² as a two to six-hour IV infusion on day 1 per chemotherapy cycle.	(TEF) Taxotere, Eloxatin and 5-fluorouracil n=88 Participants Participants administed with Docetaxel (Taxotere) 50 mg/m² as a 1-hour IV infusion day 1; Oxaliplatin (Eloxatin) 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion day 1 per chemotherapy cycle.	(TEX) Taxotere, Eloxatin and Xeloda n=82 Participants Participants administered Docetaxel (Taxotere) 50 mg/m² as a 1-hour intravenous (IV) infusion on day 1, Oxaliplatin (Eloxatin) 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine (Xeloda) 625 mg/m2 two times a day continuously per chemotherapy cycle.
Time to Progression	4.50 Months Interval 3.68 to 5.32	7.66 Months Interval 6.97 to 9.4	5.55 Months Interval 4.3 to 6.37

SECONDARY outcome

Timeframe: every 8 weeks up to a maximum of 36 months

Population: 248 participants in the full analysis population (FAP).

Percentage of partial and complete responses, according to WHO criteria: Complete Response: Disappearance of all known disease, determined by 2 observations not less than 4 weeks apart. Partial Response: Decrease by at least 50% of the diameters of all measurable lesions, determined by 2 observations not less than 4 weeks apart.

Outcome measures

Outcome measures
Measure	(TE) Taxotere and Eloxatin n=78 Participants Participants administered Docetaxel (Taxotere) 75 mg/m² as an 1-hour IV infusion on day 1 followed by Oxaliplatin (Eloxatin) 130 mg/m² as a two to six-hour IV infusion on day 1 per chemotherapy cycle.	(TEF) Taxotere, Eloxatin and 5-fluorouracil n=88 Participants Participants administed with Docetaxel (Taxotere) 50 mg/m² as a 1-hour IV infusion day 1; Oxaliplatin (Eloxatin) 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion day 1 per chemotherapy cycle.	(TEX) Taxotere, Eloxatin and Xeloda n=82 Participants Participants administered Docetaxel (Taxotere) 50 mg/m² as a 1-hour intravenous (IV) infusion on day 1, Oxaliplatin (Eloxatin) 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine (Xeloda) 625 mg/m2 two times a day continuously per chemotherapy cycle.
Best Overall Response Rate (ORR)	23.1 percentage of participants Interval 14.3 to 34.0	46.6 percentage of participants Interval 35.9 to 57.5	25.6 percentage of participants Interval 16.6 to 36.4

SECONDARY outcome

Timeframe: up to a maximum of 36 months

Population: 248 participants in the full analysis population (FAP).

The number of months measured from the date of randomization to the date of death due to any cause.

Outcome measures

Outcome measures
Measure	(TE) Taxotere and Eloxatin n=78 Participants Participants administered Docetaxel (Taxotere) 75 mg/m² as an 1-hour IV infusion on day 1 followed by Oxaliplatin (Eloxatin) 130 mg/m² as a two to six-hour IV infusion on day 1 per chemotherapy cycle.	(TEF) Taxotere, Eloxatin and 5-fluorouracil n=88 Participants Participants administed with Docetaxel (Taxotere) 50 mg/m² as a 1-hour IV infusion day 1; Oxaliplatin (Eloxatin) 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion day 1 per chemotherapy cycle.	(TEX) Taxotere, Eloxatin and Xeloda n=82 Participants Participants administered Docetaxel (Taxotere) 50 mg/m² as a 1-hour intravenous (IV) infusion on day 1, Oxaliplatin (Eloxatin) 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine (Xeloda) 625 mg/m2 two times a day continuously per chemotherapy cycle.
Overall Survival (OS)	8.97 months Interval 7.79 to 10.87	14.59 months Interval 11.7 to 21.78	11.30 months Interval 8.08 to 14.03

Adverse Events

(TE) Taxotere and Eloxatin

Serious events: 35 serious events

Other events: 75 other events

Deaths: 0 deaths

(TEF) Taxotere, Eloxatin and 5-fluorouracil

Serious events: 24 serious events

Other events: 87 other events

Deaths: 0 deaths

(TEX) Taxotere, Eloxatin and Xeloda

Serious events: 36 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

International Clinical Development Clinical Study Director

sanofi-aventis

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months after trial completion, the Investigator can publish the results. Prior to publication, the sponsor shall review the manuscript and can request changes, provided they do not jeopardize the accuracy and/or the scientific value of the publication. The approval is given in writing by the sponsor, not exceeding 90 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	(TE) Taxotere and Eloxatin n=78 participants at risk Participants administered Docetaxel (Taxotere) 75 mg/m² as an 1-hour IV infusion on day 1 followed by Oxaliplatin (Eloxatin) 130 mg/m² as a two to six-hour IV infusion on day 1 per chemotherapy cycle.	(TEF) Taxotere, Eloxatin and 5-fluorouracil n=88 participants at risk Participants administed with Docetaxel (Taxotere) 50 mg/m² as a 1-hour IV infusion day 1; Oxaliplatin (Eloxatin) 85 mg/m² simultaneously with folinic acid 400 mg/m² as a 2-hour IV infusion, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion day 1 per chemotherapy cycle.	(TEX) Taxotere, Eloxatin and Xeloda n=82 participants at risk Participants administered Docetaxel (Taxotere) 50 mg/m² as a 1-hour intravenous (IV) infusion on day 1, Oxaliplatin (Eloxatin) 100 mg/m² as a two to six-hour IV infusion on day 1, Capecitabine (Xeloda) 625 mg/m2 two times a day continuously per chemotherapy cycle.
Gastrointestinal disorders diarrhoea	61.5% 48/78 248 participants in the full analysis population (FAP) were analyzed for safety.	67.0% 59/88 248 participants in the full analysis population (FAP) were analyzed for safety.	64.6% 53/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders nausea	57.7% 45/78 248 participants in the full analysis population (FAP) were analyzed for safety.	59.1% 52/88 248 participants in the full analysis population (FAP) were analyzed for safety.	52.4% 43/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders vomiting	46.2% 36/78 248 participants in the full analysis population (FAP) were analyzed for safety.	34.1% 30/88 248 participants in the full analysis population (FAP) were analyzed for safety.	36.6% 30/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders stomatitis	24.4% 19/78 248 participants in the full analysis population (FAP) were analyzed for safety.	44.3% 39/88 248 participants in the full analysis population (FAP) were analyzed for safety.	25.6% 21/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders abdominal pain	30.8% 24/78 248 participants in the full analysis population (FAP) were analyzed for safety.	21.6% 19/88 248 participants in the full analysis population (FAP) were analyzed for safety.	19.5% 16/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders constipation	16.7% 13/78 248 participants in the full analysis population (FAP) were analyzed for safety.	17.0% 15/88 248 participants in the full analysis population (FAP) were analyzed for safety.	24.4% 20/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders abdominal pain upper	9.0% 7/78 248 participants in the full analysis population (FAP) were analyzed for safety.	13.6% 12/88 248 participants in the full analysis population (FAP) were analyzed for safety.	11.0% 9/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders dyspepsia	3.8% 3/78 248 participants in the full analysis population (FAP) were analyzed for safety.	8.0% 7/88 248 participants in the full analysis population (FAP) were analyzed for safety.	14.6% 12/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders dysphagia	7.7% 6/78 248 participants in the full analysis population (FAP) were analyzed for safety.	5.7% 5/88 248 participants in the full analysis population (FAP) were analyzed for safety.	12.2% 10/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders abdominal distension	2.6% 2/78 248 participants in the full analysis population (FAP) were analyzed for safety.	4.5% 4/88 248 participants in the full analysis population (FAP) were analyzed for safety.	6.1% 5/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Gastrointestinal disorders oral pain	5.1% 4/78 248 participants in the full analysis population (FAP) were analyzed for safety.	0.00% 0/88 248 participants in the full analysis population (FAP) were analyzed for safety.	1.2% 1/82 248 participants in the full analysis population (FAP) were analyzed for safety.
General disorders fatigue	44.9% 35/78 248 participants in the full analysis population (FAP) were analyzed for safety.	51.1% 45/88 248 participants in the full analysis population (FAP) were analyzed for safety.	47.6% 39/82 248 participants in the full analysis population (FAP) were analyzed for safety.
General disorders asthenia	26.9% 21/78 248 participants in the full analysis population (FAP) were analyzed for safety.	25.0% 22/88 248 participants in the full analysis population (FAP) were analyzed for safety.	19.5% 16/82 248 participants in the full analysis population (FAP) were analyzed for safety.
General disorders pyrexia	15.4% 12/78 248 participants in the full analysis population (FAP) were analyzed for safety.	13.6% 12/88 248 participants in the full analysis population (FAP) were analyzed for safety.	11.0% 9/82 248 participants in the full analysis population (FAP) were analyzed for safety.
General disorders oedema peripheral	10.3% 8/78 248 participants in the full analysis population (FAP) were analyzed for safety.	11.4% 10/88 248 participants in the full analysis population (FAP) were analyzed for safety.	14.6% 12/82 248 participants in the full analysis population (FAP) were analyzed for safety.
General disorders mucosal inflammation	1.3% 1/78 248 participants in the full analysis population (FAP) were analyzed for safety.	6.8% 6/88 248 participants in the full analysis population (FAP) were analyzed for safety.	2.4% 2/82 248 participants in the full analysis population (FAP) were analyzed for safety.
General disorders oedema	6.4% 5/78 248 participants in the full analysis population (FAP) were analyzed for safety.	3.4% 3/88 248 participants in the full analysis population (FAP) were analyzed for safety.	1.2% 1/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Nervous system disorders peripheral sensory neuropathy	34.6% 27/78 248 participants in the full analysis population (FAP) were analyzed for safety.	37.5% 33/88 248 participants in the full analysis population (FAP) were analyzed for safety.	30.5% 25/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Nervous system disorders neuropathy peripheral	15.4% 12/78 248 participants in the full analysis population (FAP) were analyzed for safety.	21.6% 19/88 248 participants in the full analysis population (FAP) were analyzed for safety.	23.2% 19/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Nervous system disorders dysgeusia	6.4% 5/78 248 participants in the full analysis population (FAP) were analyzed for safety.	26.1% 23/88 248 participants in the full analysis population (FAP) were analyzed for safety.	14.6% 12/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Nervous system disorders paraesthesia	14.1% 11/78 248 participants in the full analysis population (FAP) were analyzed for safety.	18.2% 16/88 248 participants in the full analysis population (FAP) were analyzed for safety.	7.3% 6/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Nervous system disorders dizziness	9.0% 7/78 248 participants in the full analysis population (FAP) were analyzed for safety.	8.0% 7/88 248 participants in the full analysis population (FAP) were analyzed for safety.	4.9% 4/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Nervous system disorders headache	5.1% 4/78 248 participants in the full analysis population (FAP) were analyzed for safety.	6.8% 6/88 248 participants in the full analysis population (FAP) were analyzed for safety.	9.8% 8/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Nervous system disorders dysaesthesia	2.6% 2/78 248 participants in the full analysis population (FAP) were analyzed for safety.	1.1% 1/88 248 participants in the full analysis population (FAP) were analyzed for safety.	7.3% 6/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Nervous system disorders neurotoxicity	5.1% 4/78 248 participants in the full analysis population (FAP) were analyzed for safety.	3.4% 3/88 248 participants in the full analysis population (FAP) were analyzed for safety.	0.00% 0/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Skin and subcutaneous tissue disorders alopecia	32.1% 25/78 248 participants in the full analysis population (FAP) were analyzed for safety.	53.4% 47/88 248 participants in the full analysis population (FAP) were analyzed for safety.	43.9% 36/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Skin and subcutaneous tissue disorders nail disorder	6.4% 5/78 248 participants in the full analysis population (FAP) were analyzed for safety.	12.5% 11/88 248 participants in the full analysis population (FAP) were analyzed for safety.	20.7% 17/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Skin and subcutaneous tissue disorders skin reaction	5.1% 4/78 248 participants in the full analysis population (FAP) were analyzed for safety.	5.7% 5/88 248 participants in the full analysis population (FAP) were analyzed for safety.	15.9% 13/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Skin and subcutaneous tissue disorders palmar-plantar erythrodysaesthesia syndrome	6.4% 5/78 248 participants in the full analysis population (FAP) were analyzed for safety.	4.5% 4/88 248 participants in the full analysis population (FAP) were analyzed for safety.	12.2% 10/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Skin and subcutaneous tissue disorders rash	3.8% 3/78 248 participants in the full analysis population (FAP) were analyzed for safety.	6.8% 6/88 248 participants in the full analysis population (FAP) were analyzed for safety.	6.1% 5/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Skin and subcutaneous tissue disorders dry skin	1.3% 1/78 248 participants in the full analysis population (FAP) were analyzed for safety.	2.3% 2/88 248 participants in the full analysis population (FAP) were analyzed for safety.	7.3% 6/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Metabolism and nutrition disorders decreased appetite	41.0% 32/78 248 participants in the full analysis population (FAP) were analyzed for safety.	40.9% 36/88 248 participants in the full analysis population (FAP) were analyzed for safety.	45.1% 37/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Respiratory, thoracic and mediastinal disorders dyspnoea	20.5% 16/78 248 participants in the full analysis population (FAP) were analyzed for safety.	12.5% 11/88 248 participants in the full analysis population (FAP) were analyzed for safety.	11.0% 9/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Respiratory, thoracic and mediastinal disorders cough	6.4% 5/78 248 participants in the full analysis population (FAP) were analyzed for safety.	10.2% 9/88 248 participants in the full analysis population (FAP) were analyzed for safety.	6.1% 5/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Respiratory, thoracic and mediastinal disorders epistaxis	1.3% 1/78 248 participants in the full analysis population (FAP) were analyzed for safety.	11.4% 10/88 248 participants in the full analysis population (FAP) were analyzed for safety.	1.2% 1/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Respiratory, thoracic and mediastinal disorders oropharyngeal pain	2.6% 2/78 248 participants in the full analysis population (FAP) were analyzed for safety.	6.8% 6/88 248 participants in the full analysis population (FAP) were analyzed for safety.	3.7% 3/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Respiratory, thoracic and mediastinal disorders hiccups	2.6% 2/78 248 participants in the full analysis population (FAP) were analyzed for safety.	2.3% 2/88 248 participants in the full analysis population (FAP) were analyzed for safety.	7.3% 6/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Musculoskeletal and connective tissue disorders back pain	7.7% 6/78 248 participants in the full analysis population (FAP) were analyzed for safety.	4.5% 4/88 248 participants in the full analysis population (FAP) were analyzed for safety.	11.0% 9/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Musculoskeletal and connective tissue disorders pain in extremity	6.4% 5/78 248 participants in the full analysis population (FAP) were analyzed for safety.	6.8% 6/88 248 participants in the full analysis population (FAP) were analyzed for safety.	3.7% 3/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Vascular disorders hypotension	0.00% 0/78 248 participants in the full analysis population (FAP) were analyzed for safety.	3.4% 3/88 248 participants in the full analysis population (FAP) were analyzed for safety.	6.1% 5/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Psychiatric disorders insomnia	10.3% 8/78 248 participants in the full analysis population (FAP) were analyzed for safety.	4.5% 4/88 248 participants in the full analysis population (FAP) were analyzed for safety.	9.8% 8/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Psychiatric disorders anxiety	5.1% 4/78 248 participants in the full analysis population (FAP) were analyzed for safety.	2.3% 2/88 248 participants in the full analysis population (FAP) were analyzed for safety.	3.7% 3/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Investigations weight decreased	6.4% 5/78 248 participants in the full analysis population (FAP) were analyzed for safety.	8.0% 7/88 248 participants in the full analysis population (FAP) were analyzed for safety.	9.8% 8/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Blood and lymphatic system disorders neutropenia	1.3% 1/78 248 participants in the full analysis population (FAP) were analyzed for safety.	5.7% 5/88 248 participants in the full analysis population (FAP) were analyzed for safety.	1.2% 1/82 248 participants in the full analysis population (FAP) were analyzed for safety.
Blood and lymphatic system disorders febrile neutropenia	5.1% 4/78 248 participants in the full analysis population (FAP) were analyzed for safety.	0.00% 0/88 248 participants in the full analysis population (FAP) were analyzed for safety.	1.2% 1/82 248 participants in the full analysis population (FAP) were analyzed for safety.