Trial Outcomes & Findings for Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E (NCT NCT01586195)

Last Updated: 2017-05-25

Results Overview

BORR was assessed by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. BORR was defined as the number of participants whose best overall response was a complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a \>/=30% decrease under baseline of the sum of diameters of all target lesions. BORR was summarized along with the associated exact 95% confidence interval (CI) using the method of Clopper-Pearson.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Up to 42 months

Results posted on

2017-05-25

Participant Flow

Participant milestones

Participant milestones
Measure	Vemurafenib Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 milligram (mg) orally twice daily (BID) until disease progression.
Overall Study STARTED	31
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Vemurafenib Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 milligram (mg) orally twice daily (BID) until disease progression.
Overall Study Death	11
Overall Study Withdrawal of Consent	5
Overall Study Started new anti-melanoma therapy	1
Overall Study Reason not specified	9

Baseline Characteristics

Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vemurafenib n=31 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Age, Continuous	60.0 years STANDARD_DEVIATION 11.39 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 42 months

Population: ITT population defined as all enrolled participants who received any amount of study drug.

Outcome measures

Outcome measures
Measure	Vemurafenib n=31 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Best Objective Response Rate (BORR)	22.6 percentage of participants Interval 9.6 to 41.1

SECONDARY outcome

Timeframe: From start of treatment up to first documentation of confirmed CR or PR (up to 42 months)

Population: ITT population defined as all enrolled participants who received any amount of study drug. Participants with a confirmed CR or PR were analyzed.

In participants with a confirmed CR or PR, time to BORR was defined as the interval between the date of first treatment and the date of first documentation of confirmed CR or PR (whichever occurred first). BORR was assessed by the investigators according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a \>/=30% decrease under baseline of the sum of diameters of all target lesions. Participants without confirmed CR or PR were censored at the date of last tumor assessment. The time to response was summarized using univariate statistics.

Outcome measures

Outcome measures
Measure	Vemurafenib n=7 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Time to BORR	1.7 months Interval 1.6 to 5.6

SECONDARY outcome

Timeframe: From date of earliest qualifying response up to date of disease progression or death (up to 42 months)

Population: ITT population defined as all enrolled participants who received any amount of study drug. Participants with a confirmed CR or PR were analyzed.

In participants with a confirmed CR or PR, duration of response was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a \>/=30% decrease under baseline of the sum of diameters of all target lesions. PD was defined as a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. Duration of response was summarized using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Vemurafenib n=7 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Duration of Response	10.7 months Interval 3.4 to 24.9

SECONDARY outcome

Timeframe: From start of treatment up to first documentation of disease progression or death (up to 42 months)

Population: ITT population defined as all enrolled participants who received any amount of study drug.

PFS was assessed by the investigators according to RECIST v1.1 and defined as the time interval between the date of the first treatment dose and the date of disease progression or death due to any cause, whichever occurred first. PD was defined as a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. PFS was summarized using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Vemurafenib n=31 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Progression-free Survival (PFS)	5.5 months Interval 1.7 to 26.5

SECONDARY outcome

Timeframe: Date of first treatment to date of death due to any cause (up to 42 months)

Population: ITT population defined as all enrolled participants who received any amount of study drug.

OS was defined as the time from the date of first treatment to the date of death due to any cause. OS was summarized using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Vemurafenib n=31 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Overall Survival (OS)	NA months Interval 3.1 to Median OS and upper limit of 95% confidence interval was not estimiable as they were not reached.

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: ITT population defined as all enrolled participants who received any amount of study drug.

Outcome measures

Outcome measures
Measure	Vemurafenib n=31 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Percentage of Participants With 6-Month Survival	82.4 percentage of participants Interval 62.6 to 92.3

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: ITT population defined as all enrolled participants who received any amount of study drug.

Outcome measures

Outcome measures
Measure	Vemurafenib n=31 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Percentage of Participants With 12-Month Survival	61.6 percentage of participants Interval 40.0 to 77.4

SECONDARY outcome

Timeframe: Up to 42 months

Population: Safety population defined as all enrolled participants who received any amount of vemurafenib on study.

An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.

Outcome measures

Outcome measures
Measure	Vemurafenib n=31 Participants Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 mg orally BID until disease progression.
Number of Participants With an Adverse Event (AE)	30 participants

Adverse Events

Vemurafenib

Serious events: 13 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vemurafenib n=31 participants at risk Participants received vemurafenib 960 mg orally BID.
Cardiac disorders Acute coronary syndrome	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Gastrointestinal disorders Abdominal pain	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Injury, poisoning and procedural complications Fall	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Metabolism and nutrition disorders Dehydration	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Metabolism and nutrition disorders Hypercalcaemia	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	19.4% 6/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Cerebrovascular accident	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Hemiplegia	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Peripheral motor neuropathy	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Tremor	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Vasogenic cerebral oedema	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.2% 1/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.

Other adverse events

Other adverse events
Measure	Vemurafenib n=31 participants at risk Participants received vemurafenib 960 mg orally BID.
Blood and lymphatic system disorders Anaemia	19.4% 6/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Blood and lymphatic system disorders Lymphopenia	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Blood and lymphatic system disorders Thrombocytopenia	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Eye disorders Vision blurred	9.7% 3/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Eye disorders Dry eye	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Gastrointestinal disorders Diarrhoea	25.8% 8/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Gastrointestinal disorders Nausea	22.6% 7/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Gastrointestinal disorders Constipation	12.9% 4/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Gastrointestinal disorders Vomiting	12.9% 4/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Gastrointestinal disorders Dyspepsia	9.7% 3/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
General disorders Fatigue	61.3% 19/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
General disorders Pyrexia	12.9% 4/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
General disorders Chills	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
General disorders Cyst	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
General disorders Mass	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
General disorders Nodule	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Infections and infestations Bacterial infection	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Infections and infestations Nasopharyngitis	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Injury, poisoning and procedural complications Sunburn	12.9% 4/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Investigations Blood creatinine increased	16.1% 5/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Investigations Weight decreased	16.1% 5/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Investigations Alanine aminotransferase increased	12.9% 4/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Investigations Aspartate aminotransferase increased	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Investigations Blood bilirubin increased	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Metabolism and nutrition disorders Decreased appetite	16.1% 5/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Metabolism and nutrition disorders Hypokalaemia	9.7% 3/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Metabolism and nutrition disorders Hyperglycaemia	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Musculoskeletal and connective tissue disorders Arthralgia	38.7% 12/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Musculoskeletal and connective tissue disorders Myalgia	19.4% 6/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.9% 4/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Musculoskeletal and connective tissue disorders Joint swelling	9.7% 3/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Musculoskeletal and connective tissue disorders Pain in extremity	9.7% 3/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	22.6% 7/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	22.6% 7/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	22.6% 7/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	12.9% 4/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibrous histiocytoma	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Headache	12.9% 4/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Disturbance of attention	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Dysaesthesia	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Nervous system disorders Hyperaesthesia	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Psychiatric disorders Anxiety	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.7% 3/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.7% 3/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Respiratory, thoracic and mediastinal disorders Cough	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Rash	41.9% 13/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Alopecia	29.0% 9/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Hyperkeratosis	29.0% 9/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Actinic keratosis	19.4% 6/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Photosensitivity reaction	19.4% 6/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Blister	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Dry skin	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Pruritus	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Rash generalised	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Sebaceous hyperplasia	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	6.5% 2/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Vascular disorders Hypertension	16.1% 5/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Vascular disorders Hypotension	9.7% 3/31 • From the randomization of the first participant to the clinical cutoff date (22 April 2015) (approximately 42 months) An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.

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