Trial Outcomes & Findings for A Study of Erlotinib (Tarceva) Versus Gemcitabine/Cisplatin as First-line Treatment in Patients With Non-small Cell Lung Cancer With EGFR Mutations (NCT NCT01342965)

Last Updated: 2015-02-24

Results Overview

The duration of progression-free survival was defined as the time from randomization to disease progression (PD) or death from any cause, whichever occurs first. PD was defined as: (1) At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (2) An unequivocal progression of existing non-target lesions. When the patient has measurable disease, the overall tumor burden must have increased sufficiently to merit discontinuation of therapy. When the patient has only non-measurable disease, the increase in overall disease burden should be comparable in magnitude to the increase that would be required to declare PD for measurable disease. (3) The appearance of new malignant lesions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

217 participants

Primary outcome timeframe

Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months)

Results posted on

2015-02-24

Participant Flow

Participant milestones

Participant milestones
Measure	Erlotinib Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Overall Study STARTED	110	107
Overall Study Received Treatment	110	104
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	109	107

Reasons for withdrawal

Reasons for withdrawal
Measure	Erlotinib Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Overall Study Death	58	57
Overall Study Lost to Follow-up	5	3
Overall Study Other Reasons- Unspecified	44	38
Overall Study Withdrawal by Subject	2	9

Baseline Characteristics

A Study of Erlotinib (Tarceva) Versus Gemcitabine/Cisplatin as First-line Treatment in Patients With Non-small Cell Lung Cancer With EGFR Mutations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erlotinib n=110 Participants Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy n=107 Participants Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.	Total n=217 Participants Total of all reporting groups
Age, Continuous	56.7 years STANDARD_DEVIATION 10.37 • n=5 Participants	55.8 years STANDARD_DEVIATION 10.41 • n=7 Participants	56.3 years STANDARD_DEVIATION 10.37 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	65 Participants n=7 Participants	133 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months)

Population: Full analysis set: All randomized participants.

Outcome measures

Outcome measures
Measure	Erlotinib n=110 Participants Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy n=107 Participants Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Investigator-assessed Duration of Progression-free Survival	11.0 Months Interval 8.3 to The upper limit of the confidence interval could not be estimated due to too few events.	5.5 Months Interval 4.2 to 7.1

SECONDARY outcome

Timeframe: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)

Population: Full analysis set: All randomized participants.

A responder was defined as a participant with either a complete response (CR) or a partial response (PR), as determined using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. A CR was defined as: (1) The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \< 10 mm. (2) The disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be non-pathological in size (\< 10 mm in the short axis). A PR was defined as: (1) At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. (2) The persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker levels above normal limits.

Outcome measures

Outcome measures
Measure	Erlotinib n=110 Participants Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy n=107 Participants Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Percentage of Responders as Assessed by the Investigator	68.2 Percentage of responders	39.3 Percentage of responders

SECONDARY outcome

Timeframe: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)

Population: Full analysis set: All randomized participants.

A participant with disease control was defined as a participant with either a complete response (CR), a partial response (PR), or stable disease (SD), as determined using RECIST v1.1. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter of TLs taking as reference the Baseline sum longest diameter (SLD). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs. A SLD for all TLs will be calculated and reported as the Baseline SLD.

Outcome measures

Outcome measures
Measure	Erlotinib n=110 Participants Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy n=107 Participants Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Percentage of Participants With Disease Control	91.8 Percentage of participants	82.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)

Population: Full analysis set: All randomized participants. Only participants who had a complete response or partial response were included in the analysis.

Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.

Outcome measures

Outcome measures
Measure	Erlotinib n=110 Participants Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy n=107 Participants Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Duration of Response	10.8 Months Interval 7.0 to 12.6	4.2 Months Interval 2.8 to 5.4

SECONDARY outcome

Timeframe: Baseline to the end of the study (3 years, 1 month)

Population: Full analysis set: All randomized participants.

Overall survival was defined as the time from the date of randomization to the date of death from any cause.

Outcome measures

Outcome measures
Measure	Erlotinib n=110 Participants Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy n=107 Participants Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Overall Survival	28.9 Months Interval 25.8 to 30.5	27.1 Months Interval 25.4 to 30.9

SECONDARY outcome

Timeframe: 36 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: approximately 21 months

Outcome measures

Outcome data not reported

Adverse Events

Erlotinib

Serious events: 22 serious events

Other events: 99 other events

Deaths: 0 deaths

Chemotherapy

Serious events: 16 serious events

Other events: 96 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Erlotinib n=110 participants at risk Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy n=104 participants at risk Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 3/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.8% 2/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.96% 1/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	1.9% 2/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Blood and lymphatic system disorders Anaemia	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	3.8% 4/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	2.9% 3/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Infections and infestations Gastroenteritis	1.8% 2/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.96% 1/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Infections and infestations Pneumonia	2.7% 3/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Infections and infestations Abscess limb	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Infections and infestations Gastrointestinal infection	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Infections and infestations Haemorrhoid infection	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Infections and infestations Localised infection	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Infections and infestations Nail bed infection	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	2.7% 3/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.8% 2/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Small intestinal haemorrhage	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.96% 1/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Vascular disorders Deep vein thrombosis	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	1.9% 2/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Vascular disorders Thrombosis	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.96% 1/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Cardiac disorders Angina pectoris	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Cardiac disorders Pericardial effusion	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Injury, poisoning and procedural complications Femur fracture	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Injury, poisoning and procedural complications Soft tissue injury	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations Blood glucose increased	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations Platelet count decreased	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.96% 1/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.96% 1/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Bone erosion	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Bone pain	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
General disorders Chest pain	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
General disorders Pyrexia	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Congenital, familial and genetic disorders Atrial septal defect	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.96% 1/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Nervous system disorders Spinal cord compression	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Psychiatric disorders Bipolar disorder	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Surgical and medical procedures Haemorrhoid operation	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.

Measure	Erlotinib n=110 participants at risk Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Chemotherapy n=104 participants at risk Participants received gemcitabine 1250 mg/m\^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m\^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Gastrointestinal disorders Nausea	4.5% 5/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	57.7% 60/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	6.4% 7/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	53.8% 56/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	44.5% 49/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	8.7% 9/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Constipation	1.8% 2/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	18.3% 19/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Mouth ulceration	5.5% 6/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	2.9% 3/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Gastrointestinal disorders Stomatitis	5.5% 6/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Blood and lymphatic system disorders Leukopenia	6.4% 7/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	49.0% 51/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Blood and lymphatic system disorders Neutropenia	4.5% 5/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	51.0% 53/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Blood and lymphatic system disorders Anaemia	7.3% 8/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	42.3% 44/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Blood and lymphatic system disorders Thrombocytopenia	1.8% 2/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	17.3% 18/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash	70.9% 78/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	10.6% 11/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	10.0% 11/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	6.7% 7/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Alopecia	5.5% 6/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	9.6% 10/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Dry skin	9.1% 10/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	1.9% 2/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Dermatitis acneiform	8.2% 9/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations White blood cell count decreased	2.7% 3/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	15.4% 16/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations Alanine aminotransferase increased	11.8% 13/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	1.9% 2/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations Platelet count decreased	0.91% 1/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	13.5% 14/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations Aspartate aminotransferase increased	10.0% 11/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	2.9% 3/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations Neutrophil count decreased	1.8% 2/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	9.6% 10/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations Blood bilirubin increased	10.0% 11/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Investigations Haemoglobin decreased	0.00% 0/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	5.8% 6/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Metabolism and nutrition disorders Decreased appetite	12.7% 14/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	28.8% 30/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	5.5% 6/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	6.7% 7/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
General disorders Fatigue	5.5% 6/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	19.2% 20/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
General disorders Pyrexia	7.3% 8/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	12.5% 13/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
General disorders Chest discomfort	5.5% 6/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	2.9% 3/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Nervous system disorders Dizziness	6.4% 7/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	13.5% 14/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Nervous system disorders Headache	4.5% 5/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	6.7% 7/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	17.3% 19/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	8.7% 9/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Infections and infestations Paronychia	15.5% 17/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	0.00% 0/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	7.3% 8/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	5.8% 6/104 Safety analysis set: All participants who had received at least 1 dose of study medication.
Psychiatric disorders Insomnia	4.5% 5/110 Safety analysis set: All participants who had received at least 1 dose of study medication.	7.7% 8/104 Safety analysis set: All participants who had received at least 1 dose of study medication.