Effect of Food Upon Pharmacokinetics of Single Oral Dose of Cediranib (AZD2171, Recentin™)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00306891
• Collaborator: (none)
• Enrollment: 60
• Locations: 4
• Arms: 4
• Duration (Months): 27
• Patients Per Site: 15
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether food has any effect on a single dose of Cediranib (AZD2171, Recentin™)followed by an assessment of the safety and tolerability of fixed daily dosing in comparison to varying dose levels on a patient-by-patient basis.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: Cediranib; Drug: Cediranib 30 - 90 mg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Randomised, Phase 2 Study in Patients With Advanced Solid Tumours to Determine Effect of Food Upon Pharmacokinetics of a Single Oral Dose of Cediranib (AZD2171, Recentin™), Followed by an Assessment of the Safety & Tolerability of Fixed and Individualised Daily Dosing
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cediranib 45 mg Fed Part A: Cediranib 45 mg Fed State	Drug: Cediranib; 45 mg oral dose; Other Names: RECENTIN™
Experimental: Cediranib 45 mg Fasted Part A: Cediranib 45 mg Fasted State	Drug: Cediranib; 45 mg oral dose; Other Names: RECENTIN™
Experimental: Cediranib 45 mg Fixed Dose Part B: Cediranib 45 mg Fixed Dose	Drug: Cediranib; 45 mg oral dose; Other Names: RECENTIN™
Experimental: Cediranib 30 - 90 mg Dose Escalation Part B: Cediranib 30 - 90 mg Dose Escalation	Drug: Cediranib 30 - 90 mg; oral tablet dose escalation; Other Names: RECENTIN™

Outcome Measures

Primary Outcome Measures

1. Part A: Area Under Plasma Concentration-time Curve (AUC) [Measurements were collected up to 168 hours (following single dosing).]

   Area under plasma concentration-time curve from zero to infinity

2. Part A: Maximum Plasma (Peak) Concentration (Cmax) [Measurements were collected up to 168 hours (following single dosing).]

   Maximum plasma drug concentration

Secondary Outcome Measures

1. Part A: AUC (0-t) [Measurements were collected up to 168 hours (following single dosing).]

   Area under the curve from time 0 to the last measureable time point

2. Part A: Time to Peak or Maximum Concentration (Tmax) [Measurements were collected up to 168 hours (following single dosing).]

   Time to reach peak or maximum concentration or maximum response

3. Part A: Terminal Phase Half-life (t1/2λz) [Measurements were collected up to 168 hours (following single dosing).]

   Terminal phase half-life

4. Part A: Apparent Total Body Clearance (CL/F) [Measurements were collected up to 168 hours (following single dosing).]

   Apparent total body clearance of drug from plasma

5. Part B: Best Overall Response Rate (ORR) [Baseline, week 8, week 16 and every 8 weeks thereafter until discontinuation.]

   Evaluation of target lesions Complete Response(CR)Disappearance of all target lesions Partial Response(PR) At least a 30% decrease in the sum of LD(longest diameter)of target lesions taking as reference the baseline sum LD.Progressive Disease(PD).At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded(either at baseline or at previous assessment since treatment began).Stable Disease(SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.Note: Appearance of new lesions only counts towards the overall visit response,not towards the response of target or non-target lesions. Evaluation of non-target lesions Complete Response(CR)Disappearance of all non-target lesions Non-Complete Response(non-CR/Non-Progression[non-PD])Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits.Progression(PD)Unequivocal progression of existing non-target lesions

6. Part B: Progression-free Survival (PFS) [Number of days from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression.]

   Target lesions: Progressive Disease (PD) At least a 20% increase in the sum of LD (longest diameter)of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began). Non target lesions: Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits. Progression (PD) Unequivocal progression of existing non-target lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of advanced solid tumour.

• Ability to eat a high fat breakfast

Exclusion Criteria:

• Poorly controlled high blood pressure.

• History of significant gastrointestinal problems

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Glasgow		United Kingdom
2	Research Site	Headington		United Kingdom
3	Research Site	London		United Kingdom
4	Research Site	Manchester		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: AstraZeneca AZD2171 Medical Science Director, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00306891
• Other Study ID Numbers: D8480C00021; 2005-003441-13
• First Posted: Mar 27, 2006
• Last Update Posted: Nov 1, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by AstraZeneca: Advanced solid tumours; Advanced cancer; tumor; tumour; RECENTIN
• Additional relevant MeSH terms: Cediranib

Study Results

Participant Flow

Recruitment Details	This was a two part study.Part A had two arms, fed/fasted and fasted/fed. Part B had two arms, a fixed dose arm and a dose escalation arm.Patients(pts)in Part A were allowed to go in to Part B. Pts who chose not to go in to Part B discontinued the study.Additionally new pts were recruited to Part B. In Parts A/B, there was a total of 60 pts.
Pre-assignment Detail	60 patients were enrolled though only 45 patients were randomized to Part A and 47 to Part B. Completion of Part B means completed at least 16 weeks of treatment.

Arm/Group Title	Cediranib 45 mg Fed	Cediranib 45 mg Fasted	Cediranib 45 mg Fixed Dose	Cediranib 30 to 90 mg Dose Escalation
Arm/Group Description	Part A: Cediranib 45 mg Fed State	Part A: Cediranib 45 mg Fasted State	Part B: Cediranib 45 mg Fixed Dose	Part B: Cediranib Dose Escalation
Period Title: Part A
STARTED	23	22	0	0
COMPLETED	18	16	0	0
NOT COMPLETED	5	6	0	0
Period Title: Part A
STARTED	0	0	16	31
COMPLETED	0	0	5	14
NOT COMPLETED	0	0	11	17

Baseline Characteristics

Arm/Group Title	Cediranib 45 mg Fed	Cediranib 45 mg Fasted	Cediranib 45 mg Fixed Dose	Cediranib 30 to 90 mg Dose Escalation	Total
Arm/Group Description	Part A: Cediranib 45 mg Fed State	Part A: Cediranib 45 mg Fasted State	Part B: Cediranib 45 mg Fixed Dose	Part B: Cediranib Dose Escalation	Total of all reporting groups
Overall Participants	23	22	16	31	92
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.6 (10.6)	51.2 (14.8)	56.4 (13.1)	56.0 (13.5)	56.0 (13.0)
Sex/Gender, Customized (participants) [Number]
Female, Part A	10 43.5%	10 45.5%	NA NaN	NA NaN	20 21.7%
Male, Part A	13 56.5%	12 54.5%	NA NaN	NA NaN	25 27.2%
Female, Part B	NA NaN	NA NaN	8 50%	12 38.7%	20 21.7%
Male, Part B	NA NaN	NA NaN	8 50%	19 61.3%	27 29.3%

Outcome Measures

1. Primary Outcome

Title	Part A: Area Under Plasma Concentration-time Curve (AUC)
Description	Area under plasma concentration-time curve from zero to infinity
Time Frame	Measurements were collected up to 168 hours (following single dosing).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cediranib 45 mg Fed	Cediranib 45 mg Fasted
Arm/Group Description	Part A: Cediranib 45 mg Fed State	Part A: Cediranib 45 mg Fasted State
Measure Participants	30	32
Geometric Mean (Full Range) [ng*h/mL]	1920	2392

2. Primary Outcome

Title	Part A: Maximum Plasma (Peak) Concentration (Cmax)
Description	Maximum plasma drug concentration
Time Frame	Measurements were collected up to 168 hours (following single dosing).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - Cediranib 45 mg Fed	Arm 2 - Cediranib 45 mg Fasted
Arm/Group Description	Part A: Cediranib 45 mg Fed State	Part A: Cediranib 45 mg Fasted State
Measure Participants	31	33
Geometric Mean (Full Range) [ng/mL]	87.02	127.9

3. Secondary Outcome

Title	Part A: AUC (0-t)
Description	Area under the curve from time 0 to the last measureable time point
Time Frame	Measurements were collected up to 168 hours (following single dosing).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - Cediranib 45 mg Fed	Arm 2 - Cediranib 45 mg Fasted
Arm/Group Description	Part A: Cediranib 45 mg Fed State	Part A: Cediranib 45 mg Fasted State
Measure Participants	30	32
Geometric Mean (Full Range) [ng*h/mL]	1896	2348

4. Secondary Outcome

Title	Part A: Time to Peak or Maximum Concentration (Tmax)
Description	Time to reach peak or maximum concentration or maximum response
Time Frame	Measurements were collected up to 168 hours (following single dosing).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - Cediranib 45 mg Fed	Arm 2 - Cediranib 45 mg Fasted
Arm/Group Description	Part A: Cediranib 45 mg Fed State	Part A: Cediranib 45 mg Fasted State
Measure Participants	31	33
Geometric Mean (Full Range) [hr]	4.59	3.52

5. Secondary Outcome

Title	Part A: Terminal Phase Half-life (t1/2λz)
Description	Terminal phase half-life
Time Frame	Measurements were collected up to 168 hours (following single dosing).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - Cediranib 45 mg Fed	Arm 2 - Cediranib 45 mg Fasted
Arm/Group Description	Part A: Cediranib 45 mg Fed State	Part A: Cediranib 45 mg Fasted State
Measure Participants	30	32
Geometric Mean (Full Range) [hr]	23.99	24.72

6. Secondary Outcome

Title	Part A: Apparent Total Body Clearance (CL/F)
Description	Apparent total body clearance of drug from plasma
Time Frame	Measurements were collected up to 168 hours (following single dosing).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - Cediranib 45 mg Fed	Arm 2 - Cediranib 45 mg Fasted
Arm/Group Description	Part A: Cediranib 45 mg Fed State	Part A: Cediranib 45 mg Fasted State
Measure Participants	30	32
Geometric Mean (Full Range) [L/h]	23.44	18.81

7. Secondary Outcome

Title	Part B: Best Overall Response Rate (ORR)
Description	Evaluation of target lesions Complete Response(CR)Disappearance of all target lesions Partial Response(PR) At least a 30% decrease in the sum of LD(longest diameter)of target lesions taking as reference the baseline sum LD.Progressive Disease(PD).At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded(either at baseline or at previous assessment since treatment began).Stable Disease(SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.Note: Appearance of new lesions only counts towards the overall visit response,not towards the response of target or non-target lesions. Evaluation of non-target lesions Complete Response(CR)Disappearance of all non-target lesions Non-Complete Response(non-CR/Non-Progression[non-PD])Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits.Progression(PD)Unequivocal progression of existing non-target lesions
Time Frame	Baseline, week 8, week 16 and every 8 weeks thereafter until discontinuation.

Outcome Measure Data

Analysis Population Description

ITT (intention-to-treat ) patients with baseline RECIST data

Arm/Group Title	Arm 3 - Cediranib 45 mg Fixed Dose	Arm 4 - Cediranib 30-90 mg Dose Escalation
Arm/Group Description	Part B: Cediranib 45 mg Fixed Dose	Part B: Cediranib 30-90 mg Dose Escalation
Measure Participants	15	29
Number [Participants]	1 4.3%	3 13.6%

8. Secondary Outcome

Title	Part B: Progression-free Survival (PFS)
Description	Target lesions: Progressive Disease (PD) At least a 20% increase in the sum of LD (longest diameter)of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began). Non target lesions: Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits. Progression (PD) Unequivocal progression of existing non-target lesions.
Time Frame	Number of days from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression.

Outcome Measure Data

Analysis Population Description

ITT (intention-to-treat ) patients with baseline RECIST data.One patient was randomized and had baseline RECIST assessments, but did not have any further RECIST assessments. Therefore they were censored at baseline, meaning the lowest value in the range was set to zero.

Arm/Group Title	Arm 3 - Cediranib 45 mg Fixed Dose	Arm 4 - Cediranib 30-90 mg Dose Escalation
Arm/Group Description	Part B: Cediranib 45 mg Fixed Dose	Part B: Cediranib 30-90 mg Dose Escalation
Measure Participants	15	29
Median (Full Range) [Days]	135	139

Adverse Events

Arm/Group Title	Cediranib 45 mg Part A		Cediranib 45 mg Fixed Dose		Cediranib 30 - 90 mg Dose Escalation
Arm/Group Description	Part A: Cediranib 45 mg		Part B: Cediranib 45 mg Fixed Dose		Cediranib 30 - 90 mg Dose Escalation
All Cause Mortality
	Cediranib 45 mg Part A		Cediranib 45 mg Fixed Dose		Cediranib 30 - 90 mg Dose Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cediranib 45 mg Part A		Cediranib 45 mg Fixed Dose		Cediranib 30 - 90 mg Dose Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/39 (15.4%)		9/16 (56.3%)		20/31 (64.5%)
Cardiac disorders
Angina Pectoris	1/39 (2.6%)		1/16 (6.3%)		0/31 (0%)
Cardiac Failure	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Gastrointestinal disorders
Abdominal Pain	0/39 (0%)		2/16 (12.5%)		3/31 (9.7%)
Diarrhoea	0/39 (0%)		1/16 (6.3%)		3/31 (9.7%)
Vomiting	0/39 (0%)		0/16 (0%)		3/31 (9.7%)
Abdominal Pain Lower	1/39 (2.6%)		0/16 (0%)		0/31 (0%)
Constipation	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Duodenitis	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Enteritis	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Gastric Perforation	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Gastric Ulcer	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Gastrointestinal Haemorrhage	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Gastrointestinal Perforation	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Intestinal Perforation	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Large Intestine Perforation	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
General disorders
Non-Cardiac Chest Pain	1/39 (2.6%)		0/16 (0%)		0/31 (0%)
Pain	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Pyrexia	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Hepatobiliary disorders
Bile Duct Obstruction	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Jaundice Cholestatic	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Infections and infestations
Central Line Infection	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Clostridial Infection	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Sepsis	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Urinary Tract Infection	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Viral Labyrinthitis	1/39 (2.6%)		0/16 (0%)		0/31 (0%)
Injury, poisoning and procedural complications
Tracheostomy Malfunction	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Metabolism and nutrition disorders
Dehydration	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Hypercalcaemia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Pathological Fracture	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial Tumour Haemorrhage	1/39 (2.6%)		0/16 (0%)		0/31 (0%)
Nervous system disorders
Spinal Cord Compression	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Psychiatric disorders
Suicide Attempt	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Renal and urinary disorders
Renal Disorder	1/39 (2.6%)		0/16 (0%)		0/31 (0%)
Urinary Retention	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Hydropneumothorax	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Pleural Effusion	1/39 (2.6%)		0/16 (0%)		0/31 (0%)
Pulmonary Embolism	0/39 (0%)		0/16 (0%)		1/31 (3.2%)
Vascular disorders
Hypertension	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Cediranib 45 mg Part A		Cediranib 45 mg Fixed Dose		Cediranib 30 - 90 mg Dose Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/39 (87.2%)		16/16 (100%)		31/31 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	0/39 (0%)		2/16 (12.5%)		3/31 (9.7%)
Anaemia	0/39 (0%)		2/16 (12.5%)		1/31 (3.2%)
Haemoglobinaemia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Lymphadenopathy	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Cardiac disorders
Bradycardia	2/39 (5.1%)		0/16 (0%)		1/31 (3.2%)
Bundle Branch Block Right	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Ear and labyrinth disorders
Deafness Unilateral	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Endocrine disorders
Hypothyroidism	0/39 (0%)		1/16 (6.3%)		4/31 (12.9%)
Eye disorders
Dry Eye	0/39 (0%)		2/16 (12.5%)		0/31 (0%)
Visual Disturbance	0/39 (0%)		0/16 (0%)		2/31 (6.5%)
Gastrointestinal disorders
Diarrhoea	5/39 (12.8%)		13/16 (81.3%)		25/31 (80.6%)
Nausea	9/39 (23.1%)		11/16 (68.8%)		17/31 (54.8%)
Vomiting	4/39 (10.3%)		10/16 (62.5%)		14/31 (45.2%)
Constipation	4/39 (10.3%)		10/16 (62.5%)		10/31 (32.3%)
Abdominal Pain	1/39 (2.6%)		4/16 (25%)		9/31 (29%)
Stomatitis	0/39 (0%)		4/16 (25%)		9/31 (29%)
Dry Mouth	1/39 (2.6%)		1/16 (6.3%)		4/31 (12.9%)
Dyspepsia	0/39 (0%)		3/16 (18.8%)		3/31 (9.7%)
Gastrooesophageal Reflux Disease	2/39 (5.1%)		0/16 (0%)		0/31 (0%)
Abdominal Pain Upper	1/39 (2.6%)		1/16 (6.3%)		1/31 (3.2%)
Epigastric Discomfort	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Lip Blister	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Mouth Ulceration	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Oral Pain	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Tongue Ulceration	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
General disorders
Fatigue	8/39 (20.5%)		5/16 (31.3%)		10/31 (32.3%)
Oedema Peripheral	2/39 (5.1%)		1/16 (6.3%)		4/31 (12.9%)
Pyrexia	0/39 (0%)		0/16 (0%)		2/31 (6.5%)
Unevaluable Event	0/39 (0%)		0/16 (0%)		2/31 (6.5%)
Malaise	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Infections and infestations
Oral Candidiasis	1/39 (2.6%)		1/16 (6.3%)		3/31 (9.7%)
Lower Respiratory Tract Infection	0/39 (0%)		1/16 (6.3%)		2/31 (6.5%)
Rhinitis	0/39 (0%)		2/16 (12.5%)		1/31 (3.2%)
Tooth Abscess	0/39 (0%)		2/16 (12.5%)		1/31 (3.2%)
Neutropenic Sepsis	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Pneumonia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Postoperative Wound Infection	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Urinary Tract Infection	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Vaginal Candidiasis	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Viral Infection	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Injury, poisoning and procedural complications
Contusion	1/39 (2.6%)		0/16 (0%)		2/31 (6.5%)
Investigations
Weight Decreased	1/39 (2.6%)		2/16 (12.5%)		8/31 (25.8%)
Blood Thyroid Stimulating Hormone Increased	0/39 (0%)		2/16 (12.5%)		7/31 (22.6%)
Alanine Aminotransferase Increased	0/39 (0%)		1/16 (6.3%)		2/31 (6.5%)
Blood Pressure Increased	2/39 (5.1%)		0/16 (0%)		0/31 (0%)
Aspartate Aminotransferase Increased	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Liver Function Test Abnormal	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Metabolism and nutrition disorders
Decreased Appetite	2/39 (5.1%)		4/16 (25%)		8/31 (25.8%)
Anorexia	3/39 (7.7%)		3/16 (18.8%)		6/31 (19.4%)
Alkalosis	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Hyperglycaemia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Hypokalaemia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Metabolic Acidosis	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/39 (2.6%)		1/16 (6.3%)		6/31 (19.4%)
Arthralgia	1/39 (2.6%)		2/16 (12.5%)		4/31 (12.9%)
Joint Swelling	0/39 (0%)		0/16 (0%)		3/31 (9.7%)
Musculoskeletal Pain	0/39 (0%)		0/16 (0%)		3/31 (9.7%)
Flank Pain	0/39 (0%)		0/16 (0%)		2/31 (6.5%)
Pain In Extremity	1/39 (2.6%)		0/16 (0%)		2/31 (6.5%)
Groin Pain	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Mobility Decreased	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Muscle Spasms	1/39 (2.6%)		1/16 (6.3%)		1/31 (3.2%)
Musculoskeletal Chest Pain	1/39 (2.6%)		1/16 (6.3%)		0/31 (0%)
Myalgia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Myopathy	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Nervous system disorders
Lethargy	8/39 (20.5%)		4/16 (25%)		7/31 (22.6%)
Dizziness	2/39 (5.1%)		1/16 (6.3%)		6/31 (19.4%)
Headache	2/39 (5.1%)		5/16 (31.3%)		5/31 (16.1%)
Dysgeusia	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)
Neuralgia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Sciatica	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Tremor	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Psychiatric disorders
Depression	0/39 (0%)		1/16 (6.3%)		3/31 (9.7%)
Anxiety	2/39 (5.1%)		1/16 (6.3%)		0/31 (0%)
Depressed Mood	2/39 (5.1%)		0/16 (0%)		0/31 (0%)
Insomnia	1/39 (2.6%)		1/16 (6.3%)		0/31 (0%)
Renal and urinary disorders
Proteinuria	0/39 (0%)		1/16 (6.3%)		2/31 (6.5%)
Urinary Tract Disorder	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Urine Odour Abnormal	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Reproductive system and breast disorders
Amenorrhoea	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Menorrhagia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	2/39 (5.1%)		4/16 (25%)		7/31 (22.6%)
Dyspnoea	1/39 (2.6%)		2/16 (12.5%)		3/31 (9.7%)
Pharyngolaryngeal Pain	0/39 (0%)		3/16 (18.8%)		0/31 (0%)
Cough	1/39 (2.6%)		2/16 (12.5%)		1/31 (3.2%)
Dyspnoea Exertional	0/39 (0%)		0/16 (0%)		2/31 (6.5%)
Productive Cough	0/39 (0%)		2/16 (12.5%)		0/31 (0%)
Hiccups	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Hydropneumothorax	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Skin and subcutaneous tissue disorders
Dry Skin	0/39 (0%)		3/16 (18.8%)		1/31 (3.2%)
Hyperhidrosis	0/39 (0%)		0/16 (0%)		2/31 (6.5%)
Skin Induration	0/39 (0%)		0/16 (0%)		2/31 (6.5%)
Alopecia	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Skin Hyperpigmentation	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Skin Lesion	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Vascular disorders
Hypertension	9/39 (23.1%)		10/16 (62.5%)		23/31 (74.2%)
Hypotension	0/39 (0%)		1/16 (6.3%)		0/31 (0%)
Lymphoedema	0/39 (0%)		1/16 (6.3%)		1/31 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If a Study Site or an Investigator requests permission to publish data from this study, any such publication (including oral presentations) is to be agreed with AstraZeneca prior to publication.