Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01974752
• Collaborator: (none)
• Enrollment: 152
• Locations: 31
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Selumetinib therapy in patients with metastatic uveal melanoma.

Condition or Disease	Intervention/Treatment	Phase
Metastatic; Uveal Melanoma	Drug: 75mg selumetinib; Drug: placebo; Drug: Dacarbazine	Phase 3

Detailed Description

A randomised double-blind study to assess the efficacy of selumetinib (AZD6244, Hyd-Sulfate) in combination with Dacarbazine compared with placebo in combination with Dacarbazine as first systemic therapy in patients with metastatic uveal melanoma (SUMIT)

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-Blind Study to Assess the Efficacy of Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine as First Systemic Therapy in Patients With Metastatic Uveal Melanoma (SUMIT)
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: selumetinib 75mg twice daily selumetinib 75mg twice daily in combination with dacarbazine.	Drug: 75mg selumetinib; selumetinib tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.; Drug: Dacarbazine; dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle taken in combination with either selumetinib or placebo tablets p.o. twice daily.
Placebo Comparator: placebo twice daily placebo twice daily in combination with dacarbazine.	Drug: placebo; placebo tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.; Drug: Dacarbazine; dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle taken in combination with either selumetinib or placebo tablets p.o. twice daily.

Outcome Measures

Primary Outcome Measures

1. Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine Measured as Progression Free Survival (PFS) Using BICR According to RECIST 1.1. [From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015]

   Progression free survival (PFS) using blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine in Terms of Objective Response Rate (ORR) by BICR [From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015]

   ORR at Week 6 using BICR according to RECIST 1.1

2. Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine in Terms of Change in Tumour Size at Week 6 by BICR [From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015]

   Percent change in tumour size at Week 6 using BICR according to RECIST 1.1

3. Assessment of the Overall Survival (OS) in Patients Taking Selumetinib in Combination With Dacarbazine Compared With Those Taking Placebo in Combination With Dacarbazine [From Randomization, up until death assessed up to 15th May 2015]

   Overall Survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria: Clinical diagnosis of metastatic uveal melanoma; Written consent from female or male patients aged 18 years and over. Histological or cytological confirmation of melanoma who are suitable for treatment with dacarbazine chemotherapy.

• At least one lesion that can be accurately measured at baseline as>/=10mm in the longest diameter. (except lymph nodes which must have short axis ≥15 mm) with CT or MRI and which is suitable for accurate repeated measurements

• ECOG performance status 0-1

• life expectancy >12 weeks

• Normal organ and marrow function

• Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients

• Patients should be able to swallow selumetinib/placebo capsules

Exclusion Criteria:-Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

• Previous randomisation in the present study

• Patients cannot have previously been treated with a systemic anti-cancer therapy. Patients can have prior intra-hepatic or non-systemic therapy. -Having received any of the following within the specified timeframe:

Any prior systemic anti-cancer therapy for the treatment of this current diagnosis, An investigational drug within 30 days of starting treatment or within five half-lives of the compound (whichever is the most appropriate is at the discretion of the Investigator), or have not recovered from side effects of an investigational drug Any non-systemic anti-cancer therapy which has not been cleared from the body by the time of starting study treatment Radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment Major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment, Any prior investigational therapy comprising inhibitors of RAS, RAF or MEK at any time, Previous treatment with dacarbazine. Any unresolved toxicity >CTCAE grade 2 from previous anti-cancer therapy, excluding alopecia -History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib or dacarbazine

--Symptomatic brain metastases or spinal cord compression (patients must be treated and stable off steroids and anti-convulsants for at least 1 month prior to entry into the study)

Cardiac conditions as follows:

• Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy)

• Acute coronary syndrome within 6 months prior to starting treatment

• Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy - Symptomatic heart failure (New York Heart Association [NYHA] Class II-IV,- Prior or current cardiomyopathy

• Baseline LVEF <55% measured by echocardiography or MUGA. Appropriate correction to be used if a MUGA is performed

• Severe valvular heart disease

• Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest

• QTcF >450 ms or other factors that increase the risk of QTc prolongation

• Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)

• Refractory nausea and vomiting, chronic gastrointestinal diseases (eg inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption

• History of another primary malignancy within 5 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study

• Ophthalmologic conditions:

• Current or past history of central serous retinopathy

• Current or past history of retinal vein occlusion

• IOP >21 mmHg or uncontrolled glaucoma (irrespective of IOP)

• Female patients who are breast-feeding a child and male or female patients of reproductive potential who are not employing an effective method of birth control

• Clinical judgement by the Investigator that the patient should not participate in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States
2	Research Site	Aurora	Colorado	United States
3	Research Site	Atlanta	Georgia	United States
4	Research Site	Lutherville	Maryland	United States
5	Research Site	St. Louis	Missouri	United States
6	Research Site	New York	New York	United States
7	Research Site	Philadelphia	Pennsylvania	United States
8	Research Site	Edegem		Belgium
9	Research Site	Gent		Belgium
10	Research Site	Kortrijk		Belgium
11	Research Site	Leuven		Belgium
12	Research Site	Toronto	Ontario	Canada
13	Research Site	Montreal	Quebec	Canada
14	Research Site	Olomouc		Czech Republic
15	Research Site	Praha		Czech Republic
16	Research Site	Hus		Finland
17	Research Site	Nice Cedex 2		France
18	Research Site	Paris Cedex 5		France
19	Research Site	Heidelberg		Germany
20	Research Site	München		Germany
21	Research Site	Jerusalem		Israel
22	Research Site	Ramat Gan		Israel
23	Research Site	Leiden		Netherlands
24	Research Site	Barcelona		Spain
25	Research Site	L'Hospitalet de Llobregat		Spain
26	Research Site	Sevilla		Spain
27	Research Site	Valencia		Spain
28	Research Site	Glasgow		United Kingdom
29	Research Site	Northwood		United Kingdom
30	Research Site	Nottingham		United Kingdom
31	Research Site	Swansea		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01974752
• Other Study ID Numbers: D1344C00001
• First Posted: Nov 3, 2013
• Last Update Posted: Jan 5, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by AstraZeneca: uveal melanoma
• Additional relevant MeSH terms: Melanoma; Uveal Neoplasms; Dacarbazine

Study Results

Participant Flow

Arm/Group Title	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Arm/Group Description	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Period Title: Overall Study
STARTED	97	32
COMPLETED	60	17
NOT COMPLETED	37	15

Baseline Characteristics

Arm/Group Title	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2	Total
Arm/Group Description	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2	Total of all reporting groups
Overall Participants	97	32	129
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.0 (12.28)	59.6 (11.28)	60.6 (12.01)
Age, Customized (Number) [Number]
<55 years	26 26.8%	11 34.4%	37 28.7%
>=55 years To <65 years	25 25.8%	9 28.1%	34 26.4%
>=65 years	46 47.4%	12 37.5%	58 45%
Gender (Count of Participants)
Female	42 43.3%	19 59.4%	61 47.3%
Male	55 56.7%	13 40.6%	68 52.7%
Race/Ethnicity, Customized (Number) [Number]
Other	1 1%	1 3.1%	2 1.6%
White	96 99%	31 96.9%	127 98.4%

Outcome Measures

1. Primary Outcome

Title	Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine Measured as Progression Free Survival (PFS) Using BICR According to RECIST 1.1.
Description	Progression free survival (PFS) using blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015

Outcome Measure Data

Analysis Population Description

All randomised patients and will compare the treatment groups on the basis of randomised treatment, regardless of the treatment actually received. Note, this is also known as the Full Analysis set (FAS).

Arm/Group Title	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Arm/Group Description	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Measure Participants	97	32
Number [number of progression events]	82	24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2, Placebo + Dacarbazine 1000 mg/m2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3195
	Comments
	Method	Log Rank
	Comments	Factor for treatment and liver metastases
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favours Selumetinib in combination with Dacarbazine

2. Secondary Outcome

Title	Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine in Terms of Objective Response Rate (ORR) by BICR
Description	ORR at Week 6 using BICR according to RECIST 1.1
Time Frame	From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Arm/Group Description	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Measure Participants	97	32
Number [number of responders]	3	0

3. Secondary Outcome

Title	Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine in Terms of Change in Tumour Size at Week 6 by BICR
Description	Percent change in tumour size at Week 6 using BICR according to RECIST 1.1
Time Frame	From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015

Outcome Measure Data

Analysis Population Description

All randomised patients and will compare the treatment groups on the basis of randomised treatment, regardless of the treatment actually received. Note, this is also known as the Full Analysis set (FAS).

Arm/Group Title	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Arm/Group Description	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Measure Participants	92	27
Mean (Standard Deviation) [percent change]	6.94 (18.001)	19.76 (38.264)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2, Placebo + Dacarbazine 1000 mg/m2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1284
	Comments
	Method	ANCOVA
	Comments	ANCOVA of log (W6/BL) tumour assessments with a factor for trt, and covariates for liver mets, log BL tumour size, and time from BL scan to rand.
Method of Estimation	Estimation Parameter	Geometric LS mean ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	A geometric least squares mean ratio < 1 favours Selumetinib in combination with Dacarbazine

4. Secondary Outcome

Title	Assessment of the Overall Survival (OS) in Patients Taking Selumetinib in Combination With Dacarbazine Compared With Those Taking Placebo in Combination With Dacarbazine
Description	Overall Survival
Time Frame	From Randomization, up until death assessed up to 15th May 2015

Outcome Measure Data

Analysis Population Description

All randomised patients and will compare the treatment groups on the basis of randomised treatment, regardless of the treatment actually received. Note, this is also known as the Full Analysis set (FAS).

Arm/Group Title	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Arm/Group Description	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2	Placebo + Dacarbazine 1000 mg/m2
Measure Participants	97	32
Number [Number of Overall Survival Events]	34	14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2, Placebo + Dacarbazine 1000 mg/m2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4011
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.39 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From informed consent up until end of double blind period
Arm/Group Title	Placebo + Dacarbazine 1000 mg/m2		Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2
Arm/Group Description	Placebo + Dacarbazine 1000 mg/m2		Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2
All Cause Mortality
	Placebo + Dacarbazine 1000 mg/m2		Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo + Dacarbazine 1000 mg/m2		Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/32 (6.3%)		20/97 (20.6%)
Blood and lymphatic system disorders
FEBRILE BONE MARROW APLASIA	0/32 (0%)	0	1/97 (1%)	1
FEBRILE NEUTROPENIA	1/32 (3.1%)	1	1/97 (1%)	1
PANCYTOPENIA	0/32 (0%)	0	1/97 (1%)	1
THROMBOCYTOPENIA	0/32 (0%)	0	1/97 (1%)	1
Cardiac disorders
ATRIAL FLUTTER	0/32 (0%)	0	1/97 (1%)	1
CARDIAC FAILURE	0/32 (0%)	0	1/97 (1%)	1
PERICARDIAL EFFUSION	0/32 (0%)	0	1/97 (1%)	1
Eye disorders
RETINAL VEIN OCCLUSION	0/32 (0%)	0	1/97 (1%)	1
Gastrointestinal disorders
CONSTIPATION	0/32 (0%)	0	1/97 (1%)	2
DIARRHOEA	1/32 (3.1%)	1	0/97 (0%)	0
VOMITING	0/32 (0%)	0	1/97 (1%)	1
General disorders
ASTHENIA	0/32 (0%)	0	1/97 (1%)	1
CHEST PAIN	0/32 (0%)	0	1/97 (1%)	1
PYREXIA	0/32 (0%)	0	2/97 (2.1%)	2
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	0/32 (0%)	0	1/97 (1%)	1
Immune system disorders
DRUG HYPERSENSITIVITY	0/32 (0%)	0	1/97 (1%)	1
Infections and infestations
PNEUMONIA	0/32 (0%)	0	1/97 (1%)	1
DEVICE RELATED SEPSIS	0/32 (0%)	0	1/97 (1%)	1
STREPTOCOCCAL BACTERAEMIA	0/32 (0%)	0	1/97 (1%)	1
URINARY TRACT INFECTION	1/32 (3.1%)	1	2/97 (2.1%)	2
Injury, poisoning and procedural complications
FALL	0/32 (0%)	0	1/97 (1%)	1
HIP FRACTURE	0/32 (0%)	0	1/97 (1%)	1
Investigations
BLOOD BILIRUBIN INCREASED	0/32 (0%)	0	1/97 (1%)	1
BLOOD CREATININE INCREASED	0/32 (0%)	0	1/97 (1%)	1
TRANSAMINASES INCREASED	0/32 (0%)	0	1/97 (1%)	1
Musculoskeletal and connective tissue disorders
NECK PAIN	0/32 (0%)	0	1/97 (1%)	1
Renal and urinary disorders
HAEMATURIA	0/32 (0%)	0	1/97 (1%)	1
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION	0/32 (0%)	0	1/97 (1%)	1
PULMONARY EMBOLISM	0/32 (0%)	0	1/97 (1%)	1
Skin and subcutaneous tissue disorders
URTICARIA	0/32 (0%)	0	1/97 (1%)	1
Vascular disorders
HYPOTENSION	0/32 (0%)	0	1/97 (1%)	1
Other (Not Including Serious) Adverse Events
	Placebo + Dacarbazine 1000 mg/m2		Selumetinib 75 mg BD + Dacarbazine 1000 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/32 (100%)		97/97 (100%)
Blood and lymphatic system disorders
ANAEMIA	4/32 (12.5%)	6	18/97 (18.6%)	22
NEUTROPENIA	11/32 (34.4%)	14	25/97 (25.8%)	35
THROMBOCYTOPENIA	4/32 (12.5%)	4	26/97 (26.8%)	39
LEUKOPENIA	3/32 (9.4%)	3	0/97 (0%)	0
Eye disorders
VISION BLURRED	1/32 (3.1%)	1	10/97 (10.3%)	11
Gastrointestinal disorders
CONSTIPATION	14/32 (43.8%)	19	37/97 (38.1%)	46
ABDOMINAL PAIN	3/32 (9.4%)	3	11/97 (11.3%)	12
ABDOMINAL PAIN UPPER	3/32 (9.4%)	4	8/97 (8.2%)	8
DIARRHOEA	7/32 (21.9%)	11	43/97 (44.3%)	83
DRY MOUTH	2/32 (6.3%)	2	9/97 (9.3%)	9
DYSPEPSIA	2/32 (6.3%)	2	11/97 (11.3%)	12
GASTROINTESTINAL PAIN	2/32 (6.3%)	2	0/97 (0%)	0
GASTROOESOPHAGEAL REFLUX DISEASE	1/32 (3.1%)	1	5/97 (5.2%)	5
NAUSEA	6/32 (18.8%)	12	60/97 (61.9%)	92
STOMATITIS	2/32 (6.3%)	2	15/97 (15.5%)	16
VOMITING	6/32 (18.8%)	7	27/97 (27.8%)	36
General disorders
ASTHENIA	4/32 (12.5%)	5	20/97 (20.6%)	21
CHILLS	1/32 (3.1%)	1	5/97 (5.2%)	6
FACE OEDEMA	0/32 (0%)	0	6/97 (6.2%)	7
FATIGUE	15/32 (46.9%)	16	43/97 (44.3%)	49
OEDEMA PERIPHERAL	2/32 (6.3%)	2	42/97 (43.3%)	47
PYREXIA	5/32 (15.6%)	6	8/97 (8.2%)	9
Hepatobiliary disorders
HEPATIC PAIN	3/32 (9.4%)	3	3/97 (3.1%)	3
Infections and infestations
BRONCHITIS	0/32 (0%)	0	5/97 (5.2%)	5
LOWER RESPIRATORY TRACT INFECTION	2/32 (6.3%)	2	0/97 (0%)	0
NASOPHARYNGITIS	1/32 (3.1%)	1	5/97 (5.2%)	6
URINARY TRACT INFECTION	3/32 (9.4%)	3	9/97 (9.3%)	9
Investigations
GAMMA-GLUTAMYLTRANSFERASE INCREASED	2/32 (6.3%)	3	6/97 (6.2%)	6
ALANINE AMINOTRANSFERASE INCREASED	5/32 (15.6%)	7	28/97 (28.9%)	36
ASPARTATE AMINOTRANSFERASE INCREASED	5/32 (15.6%)	8	29/97 (29.9%)	36
BLOOD ALKALINE PHOSPHATASE INCREASED	2/32 (6.3%)	3	8/97 (8.2%)	8
BLOOD CREATINE PHOSPHOKINASE INCREASED	2/32 (6.3%)	2	36/97 (37.1%)	40
NEUTROPHIL COUNT DECREASED	1/32 (3.1%)	1	6/97 (6.2%)	8
PLATELET COUNT DECREASED	3/32 (9.4%)	4	7/97 (7.2%)	10
WEIGHT DECREASED	2/32 (6.3%)	2	1/97 (1%)	1
Metabolism and nutrition disorders
HYPERGLYCAEMIA	2/32 (6.3%)	4	4/97 (4.1%)	5
DECREASED APPETITE	9/32 (28.1%)	9	17/97 (17.5%)	18
HYPERKALAEMIA	2/32 (6.3%)	3	5/97 (5.2%)	6
HYPOALBUMINAEMIA	2/32 (6.3%)	2	6/97 (6.2%)	8
HYPONATRAEMIA	1/32 (3.1%)	1	5/97 (5.2%)	6
Musculoskeletal and connective tissue disorders
NECK PAIN	0/32 (0%)	0	5/97 (5.2%)	5
PAIN IN EXTREMITY	1/32 (3.1%)	1	5/97 (5.2%)	5
ARTHRALGIA	4/32 (12.5%)	6	5/97 (5.2%)	6
BACK PAIN	0/32 (0%)	0	9/97 (9.3%)	10
MUSCULOSKELETAL CHEST PAIN	3/32 (9.4%)	4	1/97 (1%)	1
MUSCULOSKELETAL PAIN	3/32 (9.4%)	3	4/97 (4.1%)	4
MYALGIA	1/32 (3.1%)	1	12/97 (12.4%)	14
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN	2/32 (6.3%)	2	2/97 (2.1%)	3
Nervous system disorders
PARAESTHESIA	2/32 (6.3%)	4	5/97 (5.2%)	5
DIZZINESS	3/32 (9.4%)	3	6/97 (6.2%)	7
DYSGEUSIA	3/32 (9.4%)	4	11/97 (11.3%)	11
HEADACHE	3/32 (9.4%)	3	13/97 (13.4%)	13
SYNCOPE	0/32 (0%)	0	6/97 (6.2%)	7
Psychiatric disorders
INSOMNIA	4/32 (12.5%)	4	8/97 (8.2%)	8
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	3/32 (9.4%)	3	19/97 (19.6%)	23
OROPHARYNGEAL PAIN	2/32 (6.3%)	2	4/97 (4.1%)	4
COUGH	1/32 (3.1%)	1	9/97 (9.3%)	9
EPISTAXIS	1/32 (3.1%)	1	5/97 (5.2%)	6
Skin and subcutaneous tissue disorders
DRY SKIN	0/32 (0%)	0	11/97 (11.3%)	12
ALOPECIA	1/32 (3.1%)	1	6/97 (6.2%)	6
DERMATITIS ACNEIFORM	1/32 (3.1%)	1	30/97 (30.9%)	37
HYPERHIDROSIS	3/32 (9.4%)	3	3/97 (3.1%)	3
PHOTOSENSITIVITY REACTION	2/32 (6.3%)	2	0/97 (0%)	0
PRURITUS	4/32 (12.5%)	5	14/97 (14.4%)	15
RASH	2/32 (6.3%)	2	55/97 (56.7%)	60
SKIN FISSURES	0/32 (0%)	0	12/97 (12.4%)	14
Vascular disorders
HYPERTENSION	2/32 (6.3%)	2	19/97 (19.6%)	19

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.