Phase II Study of MEDI4736 Monotherapy in Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

• ClinicalTrials.gov Identifier: NCT02207530
• Recruitment Status: Completed
• First Posted: August 4, 2014
• Results First Posted: June 18, 2018
• Last Update Posted: September 29, 2020
• Sponsor: AstraZeneca
• Collaborator: PRA Health Sciences
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent or Metastatic PD-L1-positive Squamous Cell Carcinoma of the Head and Neck
• Intervention: Drug: MEDI4736
• Enrollment: 112

Participant Flow

Recruitment Details	110 sites in 14 countries enrolled and screened patients. The study was conducted and managed by PRA, a contract research organization.
Pre-assignment Details

Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Period Title: Overall Study
Started	112
Completed	21
Not Completed	91
Reason Not Completed
Worsening condition under investigation	78
Patient decision to stop study treatment	5
Adverse Event	8

Baseline Characteristics

Arm/Group Title		MEDI4736 10 mg/kg
Arm/Group Description		MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Baseline Participants		112
Baseline Analysis Population Description		Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Age, Categorical [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	83 74.1%
	>=65 years	29 25.9%
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Age, Continuous [1]; Median (Full Range); Unit of measure: Years
	Number Analyzed	112 participants
		60.0; (24 to 84)
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants
	Female	32 28.6%
	Male	80 71.4%
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants
	Hispanic or Latino	1 0.9%
	Not Hispanic or Latino	109 97.3%
	Unknown or Not Reported	2 1.8%
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Race (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants
	American Indian or Alaska Native	0 0.0%
	Asian	4 3.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	5 4.5%
	White	100 89.3%
	More than one race	0 0.0%
	Unknown or Not Reported	3 2.7%
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Smoking/ Nicotine status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	112 participants
>10 Pack years		49
<=10 pack years		53
Unknown/ Not reported		10
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Nicotine Use [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	112 participants
Current		10
Former		59
Never		43
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
HPV status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	112 participants
Positive		34
Negative		65
Unknown/ Not reported		3
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
WHO/ECOG performance status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	112 participants
(0) Normal activity		34
(1) Restricted activity		77
Missing		1
		[1] Measure Analysis Population Description: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	Objective response rate (per RECIST 1.1 as assessed by blinded independent central review [BICR]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors [RECIST] 1.1. criteria are: Complete response [CR] = disappearance of all target lesions since baseline; and partial response [PR] = at least a 30% decrease in the sum of the diameters of target lesions.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease at baseline according to BICR

Arm/Group Title		MEDI4736 10 mg/kg
Arm/Group Description:		MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed		111
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: % of participants
Overall	Number Analyzed	111 participants
		16.2; (9.9 to 24.41)
Smoking/nicotine status >10 pack years	Number Analyzed	48 participants
		14.6; (6.07 to 27.76)
Smoking/nicotine status <=10 pack years	Number Analyzed	53 participants
		18.9; (9.44 to 31.97)
Smoking/nicotine status - Missing	Number Analyzed	10 participants
		10.0 [1]; (NA to NA)
Substance user-Current	Number Analyzed	9 participants
		11.1; (0.28 to 48.25)
Substance user-Former	Number Analyzed	59 participants
		15.3; (7.22 to 26.99)
Substance user-Never	Number Analyzed	43 participants
		18.6; (8.39 to 33.40)
HPV status-Positive	Number Analyzed	34 participants
		29.4; (15.10 to 47.48)
HPV status-Negative	Number Analyzed	64 participants
		10.9; (4.51 to 21.25)
HPV status-Missing	Number Analyzed	13 participants
		7.7 [1]; (NA to NA)

[1]

Only 1 patient in this category with a response

2. Secondary Outcome

Title	Best Objective Response
Description	Best objective response based on BICR assessments according to RECIST v1.1. Response required confirmation after 4 weeks. Unconfirmed complete (CR) or partial response (PR) refers to CR or PR achieved but either no confirmation assessment was performed or a confirmation assessment was performed but response was not confirmed.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.

Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description:	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed	111
Measure Type: Number; Unit of Measure: % of participants
Response-Total	16.2
Response-Partial response (PR)	15.3
Response-Complete response (CR)	0.9
Non-response (NR)-Total	83.8
NR-Stable disease (SD)≥8 weeks-Total	9.0
NR-SD≥8 weeks-Unconfirmed CR or PR	2.7
NR-Stable disease (SD) ≥8 weeks-SD	6.3
NR-Progression-Total	52.3
NR-Progression-RECIST 1.1 progression	25.2
NR-Progression-Death	27.0
NR-Not evaluable-Total	22.5
NR-Not evaluable-SD<8 weeks	19.8
NR-Not evaluable-Incomplete post-baseline tests	2.7

3. Secondary Outcome

Title	Duration of Response- Participants Remaining in Response
Description	Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.

Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description:	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: % of participants
Remaining in response-3 months	100
Remaining in response-6 months	76.5
Remaining in response-9 months	61.8
Remaining in response-12 months	37.1
Ongoing response	55.6

4. Secondary Outcome

Title	Duration of Response
Description	Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1. Duration of response was the time from the first documentation of complete or partial response until the date of progression (which was subsequently confirmed), death, or the last evaluable RECIST assessment for patients that did not progress. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.

Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description:	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: Participants
No. progressed or died within 12 months	6
No. progressed or died after 12 months	2

5. Secondary Outcome

Title	Time to Onset of Response From First Dose
Description	Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.

Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description:	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed	18
Median (Full Range); Unit of Measure: Months
	2.00; (1.64 to 9.20)

6. Secondary Outcome

Title	Disease Control at 6 Months
Description	Disease control (DCR) at 6 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD): Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following the start of study treatment.; Method 2: Patients who had a best objective response of CR or PR within 24 weeks or had demonstrated SD for a minimum interval of 16 weeks following the start of study treatment.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.

Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description:	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed	111
Measure Type: Number; Unit of Measure: % of participants
METHOD 1: Disease control at 6 months	23.4
METHOD 1: No disease control at 6 months	76.6
METHOD 1: No disease control:Not evaluable/missing	27.0
METHOD 2: Disease control at 6 months	33.3
METHOD 2: No disease control at 6 months	66.7
METHOD 2: No disease control:Not evaluable/missing	27.0

7. Secondary Outcome

Title	Progression-free Survival
Description	Progression status based on BICR assessments according to RECIST v1.1 at time of PFS analysis. Progression was defined as the time from the date of first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description:	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed	112
Measure Type: Number; Unit of Measure: % of participants
No progression	17.0
No progression + under follow-up	12.5
Progression-Total	83.0
RECIST 1.1 progression	50.0
Death in absence of RECIST 1.1 progression	33.0

8. Secondary Outcome

Title	Overall Survival (OS)
Description	Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status, or who were lost to follow-up.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description:	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed	112
Measure Type: Number; Unit of Measure: % of participants
Still in survival follow-up	24.1
Terminated prior to death	6.3
Voluntary discontinuation by subject	6.3
Death	69.6

9. Secondary Outcome

Title	Quality of Life
Description	Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3.; Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H&N35. Function or global health status/quality of life improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (an increase from baseline score ≥10). Symptom improvement was defined as 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10). Scale improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.

Arm/Group Title		MEDI4736 10 mg/kg
Arm/Group Description:		MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
Overall Number of Participants Analyzed		112
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: % of participants
EORTC QLQ-C30 Function-Physical	Number Analyzed	70 participants
		17.1; (10.1 to 27.6)
EORTC QLQ-C30 Function-Role	Number Analyzed	70 participants
		22.9; (14.6 to 34.0)
EORTC QLQ-C30 Function-Cognitive	Number Analyzed	62 participants
		21.0; (12.7 to 32.6)
EORTC QLQ-C30 Function-Emotional	Number Analyzed	69 participants
		15.9; (9.1 to 26.3)
EORTC QLQ-C30 Function-Social	Number Analyzed	75 participants
		34.7; (24.9 to 45.9)
EORTC QLQ-C30 Symptom-Fatigue	Number Analyzed	89 participants
		21.3; (14.1 to 31.0)
EORTC QLQ-C30 Symptom-Pain	Number Analyzed	82 participants
		26.8; (18.4 to 37.3)
EORTC QLQ-C30 Symptom-Nausea/vomiting	Number Analyzed	31 participants
		32.3; (18.6 to 49.9)
EORTC QLQ-C30 Global health status/QoL	Number Analyzed	96 participants
		13.5; (8.1 to 21.8)
EORTC QLQ-H&N35 Scale-Pain in the mouth	Number Analyzed	69 participants
		24.6; (16.0 to 36.0)
EORTC QLQ-H&N35 Scale-Swallowing	Number Analyzed	62 participants
		19.4; (11.4 to 30.9)
EORTC QLQ-H&N35 Scale-Senses	Number Analyzed	67 participants
		34.3; (24.1 to 46.3)
EORTC QLQ-H&N35 Scale-Speech	Number Analyzed	81 participants
		28.4; (19.7 to 39.0)
EORTC QLQ-H&N35 Scale-Social eating	Number Analyzed	67 participants
		22.4; (14.1 to 33.7)
EORTC QLQ-H&N35 Scale-Social contact	Number Analyzed	58 participants
		17.2; (9.6 to 28.9)
EORTC QLQ-H&N35 Scale-Sexuality	Number Analyzed	74 participants
		25.7; (17.1 to 36.7)

Adverse Events

Time Frame	From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
Adverse Event Reporting Description	AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
Arm/Group Title	MEDI4736 10 mg/kg
Arm/Group Description	MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
All-Cause Mortality
	MEDI4736 10 mg/kg
	Affected / at Risk (%)
Total	78/112 (69.64%)
Serious Adverse Events
	MEDI4736 10 mg/kg
	Affected / at Risk (%)	# Events
Total	43/112 (38.39%)
Blood and lymphatic system disorders
Anaemia † 1	1/112 (0.89%)	1
Cardiac disorders
Atrial fibrillation † 1	2/112 (1.79%)	2
Cardiac arrest † 1	1/112 (0.89%)	1
Cardiac failure † 1	1/112 (0.89%)	1
Cardiopulmonary failure † 1	1/112 (0.89%)	1
Endocrine disorders
Hypercalcaemia of malignancy † 1	1/112 (0.89%)	1
Gastrointestinal disorders
Constipation † 1	1/112 (0.89%)	1
Diarrhoea † 1	1/112 (0.89%)	1
Dysphagia † 1	2/112 (1.79%)	2
Large intestinal obstruction † 1	1/112 (0.89%)	1
Mouth haemorrhage † 1	1/112 (0.89%)	1
Oesophageal haemorrhage † 1	1/112 (0.89%)	1
Pneumatosis intestinalis † 1	1/112 (0.89%)	1
General disorders
Chest pain † 1	1/112 (0.89%)	1
Fatigue † 1	3/112 (2.68%)	4
Localised oedema † 1	1/112 (0.89%)	1
Hepatobiliary disorders
Cholecystitis † 1	1/112 (0.89%)	1
Cholelithiasis † 1	1/112 (0.89%)	1
Hepatitis † 1	1/112 (0.89%)	1
Hepatotoxicity † 1	1/112 (0.89%)	1
Infections and infestations
Abscess neck † 1	1/112 (0.89%)	1
Device related infection † 1	1/112 (0.89%)	1
Gangrene † 1	1/112 (0.89%)	3
Gastrointestinal infection † 1	1/112 (0.89%)	1
Pneumonia † 1	4/112 (3.57%)	5
Pulmonary sepsis † 1	1/112 (0.89%)	1
Septic shock † 1	1/112 (0.89%)	1
Wound infection † 1	1/112 (0.89%)	1
Injury, poisoning and procedural complications
Fall † 1	1/112 (0.89%)	1
Gastrostomy failure † 1	1/112 (0.89%)	1
Post procedural haemorrhage † 1	1/112 (0.89%)	1
Wound haemorrhage † 1	1/112 (0.89%)	1
Investigations
Alanine aminotransferase increased † 1	1/112 (0.89%)	1
Aspartate aminotransferase increased † 1	1/112 (0.89%)	1
Blood bilirubin increased † 1	1/112 (0.89%)	1
Gamma-glutamyltransferase increased † 1	1/112 (0.89%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	1/112 (0.89%)	1
Dehydration † 1	2/112 (1.79%)	2
Hypercalcaemia † 1	2/112 (1.79%)	2
Hyponatraemia † 1	1/112 (0.89%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain † 1	1/112 (0.89%)	2
Nervous system disorders
Cerebral infarction † 1	1/112 (0.89%)	1
Cerebrovascular accident † 1	1/112 (0.89%)	1
Epilepsy † 1	1/112 (0.89%)	1
Nerve compression † 1	1/112 (0.89%)	1
Seizure † 1	1/112 (0.89%)	1
Syncope † 1	1/112 (0.89%)	1
Vascular encephalopathy † 1	1/112 (0.89%)	1
Psychiatric disorders
Confusional state † 1	1/112 (0.89%)	1
Renal and urinary disorders
Nephritis † 1	1/112 (0.89%)	1
Respiratory, thoracic and mediastinal disorders
Bronchopneumopathy † 1	1/112 (0.89%)	1
Dyspnoea † 1	1/112 (0.89%)	1
Epistaxis † 1	2/112 (1.79%)	2
Hypoxia † 1	1/112 (0.89%)	1
Lung cyst † 1	1/112 (0.89%)	1
Pleural effusion † 1	2/112 (1.79%)	3
Pneumonia aspiration † 1	1/112 (0.89%)	1
Pneumonitis † 1	1/112 (0.89%)	1
Pneumothorax † 1	1/112 (0.89%)	1
Pulmonary embolism † 1	2/112 (1.79%)	2
Respiratory distress † 1	1/112 (0.89%)	1
Respiratory failure † 1	1/112 (0.89%)	1
Stridor † 1	2/112 (1.79%)	2
Tachypnoea † 1	1/112 (0.89%)	1
Vascular disorders
Haemorrhage † 1	1/112 (0.89%)	2
Superior vena cava syndrome † 1	1/112 (0.89%)	1
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	MEDI4736 10 mg/kg
	Affected / at Risk (%)	# Events
Total	93/112 (83.04%)
Blood and lymphatic system disorders
Anaemia † 1	18/112 (16.07%)	19
Endocrine disorders
Hypothyroidism † 1	15/112 (13.39%)	15
Gastrointestinal disorders
Constipation † 1	22/112 (19.64%)	27
Diarrhoea † 1	16/112 (14.29%)	28
Dysphagia † 1	11/112 (9.82%)	11
Nausea † 1	22/112 (19.64%)	28
Vomiting † 1	13/112 (11.61%)	19
General disorders
Asthenia † 1	17/112 (15.18%)	18
Fatigue † 1	26/112 (23.21%)	27
Localised oedema † 1	6/112 (5.36%)	6
Mucosal inflammation † 1	6/112 (5.36%)	6
Pyrexia † 1	10/112 (8.93%)	15
Infections and infestations
Nasopharyngitis † 1	7/112 (6.25%)	10
Urinary tract infection † 1	10/112 (8.93%)	10
Investigations
Gamma-glutamyltransferase increased † 1	7/112 (6.25%)	7
Weight decreased † 1	13/112 (11.61%)	13
Metabolism and nutrition disorders
Decreased appetite † 1	18/112 (16.07%)	21
Hypercalcaemia † 1	10/112 (8.93%)	10
Hypokalaemia † 1	7/112 (6.25%)	9
Hypomagnesaemia † 1	10/112 (8.93%)	15
Hyponatraemia † 1	8/112 (7.14%)	14
Musculoskeletal and connective tissue disorders
Arthralgia † 1	10/112 (8.93%)	15
Myalgia † 1	7/112 (6.25%)	7
Neck pain † 1	6/112 (5.36%)	6
Nervous system disorders
Dizziness † 1	11/112 (9.82%)	13
Headache † 1	10/112 (8.93%)	14
Psychiatric disorders
Insomnia † 1	10/112 (8.93%)	12
Respiratory, thoracic and mediastinal disorders
Cough † 1	12/112 (10.71%)	13
Dyspnoea † 1	15/112 (13.39%)	18
Oropharyngeal pain † 1	7/112 (6.25%)	7
Skin and subcutaneous tissue disorders
Dry skin † 1	8/112 (7.14%)	8
Pruritus † 1	12/112 (10.71%)	14
Rash † 1	7/112 (6.25%)	7
Vascular disorders
Hypotension † 1	7/112 (6.25%)	7
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

The only disclosure restriction on the PI is that the sponsor can review publications prior to public release for a period up to 120 days to confirm accuracy, prevent disclosure of confidential information, and ensure that information is handled appropriately.

Results Point of Contact

• Name/Title: Jean Fan, MD, Global Clinical Lead
• Organization: AstraZeneca LP
• Phone: 1-301-398-5080
• EMail: jean.fan@astrazeneca.com

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02207530
• Other Study ID Numbers: D4193C00001
• First Submitted: August 1, 2014
• First Posted: August 4, 2014
• Results First Submitted: March 26, 2018
• Results First Posted: June 18, 2018
• Last Update Posted: September 29, 2020