Trial Outcomes & Findings for Comparison of Two Formulations of AZD5363 and the Effect of Food on Pharmacokinetic Exposure, Safety and Tolerability (NCT NCT01895946)

NCT ID: NCT01895946

Last Updated: 2016-05-25

Results Overview

The actual sampling times were used in the pharmacokinetics (PK) parameter calculations and PK parameters were derived using standard non-compartmental methods. Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined: Maximum plasma concentration at steady state (Css max), time to Css,max (tss max), minimum plasma concentration at steady state (Css min), area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and apparent clearance (CLss/F). Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss. Ratio of Css,max for Day 4 to Day 11 have been derived.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 33 participants
• Primary outcome timeframe: Day 4 and Day 11
• Results posted on: 2016-05-25

Participant Flow

There were 2 parts to this study: Part A (tablet formulation assessment) followed by Part B (food effect assessment). Part A: first patient enrolled on 18/12/2013 and last patient completed on 16/12/2014. Part B: first patient enrolled on 10/09/2014 and last patient completed on 22/07/2015. Part A was conducted at 3 sites and Part B at 2 sites.

Note, Part A involved a cross over between tablet and capsule formulations A total of 33 patients were enrolled. 30 of these patients passed screening assessments and were dosed

Participant milestones

Measure	Part A Part A of the study	Part B Part B of the study
Overall Study STARTED	18	12
Overall Study COMPLETED	18	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Two Formulations of AZD5363 and the Effect of Food on Pharmacokinetic Exposure, Safety and Tolerability

Baseline characteristics by cohort

Measure	Part A n=18 Participants Part A of the study	Part B n=12 Participants Part B of the study	Total n=30 Participants Total of all reporting groups
Age, Customized <50 years	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Age, Customized Between 50 and 65 years	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Age, Customized >=65 years	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 4 and Day 11

Population: All patients who provided concentration-time data for AZD5363 for both capsule and tablet administration (Part A) or for both fed and fasted treatments and who were compliant with the standard dietary and evaluability requirements (Part B) were included in PK analysis set.

The actual sampling times were used in the pharmacokinetics (PK) parameter calculations and PK parameters were derived using standard non-compartmental methods.

Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined:

Maximum plasma concentration at steady state (Css max), time to Css,max (tss max), minimum plasma concentration at steady state (Css min), area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and apparent clearance (CLss/F).

Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss.

Ratio of Css,max for Day 4 to Day 11 have been derived.

Outcome measures

Measure	Part A n=11 Participants Part A of the study	Part B n=9 Participants Part B of the study
Ratio of Css,Max for Day 4 to Day 11	1.02 Ratio Interval 0.86 to 1.2	0.67 Ratio Interval 0.55 to 0.82

PRIMARY outcome

Timeframe: Day 4 and Day 11

Population: All patients who provided concentration-time data for AZD5363 for both capsule and tablet administration (Part A) or for both fed and fasted treatments and who were compliant with the standard dietary and evaluability requirements (Part B) were included in PK analysis set.

The actual sampling times were used in the parameter calculations and PK parameters were derived using standard non-compartmental methods.

Following the twice daily dosing in Cycle 1 at Day 4 and 11 for both the formulation switch and food effect investigations, the following PK parameters have been determined:

Css max, tss max, Css min, area under the plasma concentration-time curve from zero to the end of the dosing interval (AUCss) and CLss/F.

Css max, tss max were determined by inspection of the concentration-time profiles. AUCss was calculated using the linear up / log down trapezoidal rule. CLss/F was determined from the ratio of dose/AUCss.

Ratio of AUCss for Day 4 to Day 11 have been derived.

Outcome measures

Measure	Part A n=11 Participants Part A of the study	Part B n=9 Participants Part B of the study
Ratio of AUCss for Day 4 to Day 11	0.90 Ratio Interval 0.77 to 1.06	0.89 Ratio Interval 0.76 to 1.05

SECONDARY outcome

Timeframe: Assessed every 6 weeks, up to 36 weeks

Population: Modified intent-to-treat analysis set: all patients who received at least one dose of study treatment with a baseline tumour assessment.

Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 guidelines for measurable, non-measurable, target lesions (TLs) and non-target lesions (NTLs) and the objective tumour response criteria was used.

Categorisation of objective tumour response assessment was based on the RECIST 1.1 guidelines for response: CR (complete response, efined as disappearance of all target lesions), PR (partial response, defined as >=30% decrease in the sum of the longest diameter of target lesions), SD (stable disease, defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression) and PD (progression of disease, defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion). BOR was the best overall response observed across the study and up to 36 weeks. Number of subjects with response (CR or PR) is described.

Outcome measures

Measure	Part A n=18 Participants Part A of the study	Part B n=12 Participants Part B of the study
Efficacy: Best Objective Response (BOR)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Modified intent-to-treat analysis set: all patients who received at least one dose of study treatment with a baseline tumour assessment.

Disease control = confirmed complete response + confirmed partial response + stable disease at 12 weeks

Outcome measures

Measure	Part A n=18 Participants Part A of the study	Part B n=12 Participants Part B of the study
Efficacy: Disease Control at Week 12	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Modified intent-to-treat analysis set: all patients who received at least one dose of study treatment with a baseline tumour assessment.

Tumour size is the sum of the longest diameters of the target lesions. Target lesions are measurable tumour lesions.

The percentage change in target lesion tumour size at each week 12 for which data are available was obtained for each subject taking the difference between the sum of the target lesion at each week 12 and the sum of the target lesions at baseline divided by the sum of the target lesions at baseline multiplied by 100 (i.e. (week 12) - baseline)/baseline * 100).

Outcome measures

Measure	Part A n=6 Participants Part A of the study	Part B n=7 Participants Part B of the study
Efficacy: Target Lesion Size, Percentage Change From Baseline at Week 12	8.1 Percentage change from baseline Standard Deviation 14.72	-1.5 Percentage change from baseline Standard Deviation 6.49

SECONDARY outcome

Timeframe: Assessed every 6 weeks up to 36 weeks

Population: Modified intent-to-treat analysis set: all patients who received at least one dose of study treatment with a baseline tumour assessment.

Tumour size is the sum of the longest diameters of the target lesions. Target lesions are measurable tumour lesions.

best percentage change in tumour size from baseline is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction from baseline based on all post baseline assessments.

Outcome measures

Measure	Part A n=14 Participants Part A of the study	Part B n=11 Participants Part B of the study
Efficacy: Target Lesion Size, Best Percentage Change From Baseline	10.5 Percentage change from baseline Standard Deviation 13.62	0.2 Percentage change from baseline Standard Deviation 9.92

SECONDARY outcome

Timeframe: Assessed every 6 weeks up to 36 weeks

Population: Modified intent-to-treat analysis set: all patients who received at least one dose of study treatment with a baseline tumour assessment.

PFS is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the subject withdraws from randomised therapy or receives another anti-cancer therapy prior to progression. Subjects who have not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions.

Outcome measures

Measure	Part A n=18 Participants Part A of the study	Part B n=12 Participants Part B of the study
Efficacy: Progression-free Survival (PFS)	6.1 weeks Inter-Quartile Range 13.62 • Interval 5.0 to 16.7	13.7 weeks Inter-Quartile Range 9.92 • Interval 11.1 to 35.4

Adverse Events

Part A

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Part B

Serious events: 6 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A n=18 participants at risk Part A of the study	Part B n=12 participants at risk Part B of the study
General disorders Pyrexia	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Diarrhoea	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	25.0% 3/12 • Number of events 3 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Pneumonia mycoplasmal	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Intestinal obstruction	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Mouth haemorrhage	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Vomiting	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Stomatitis	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Rash papular	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.

Other adverse events

Measure	Part A n=18 participants at risk Part A of the study	Part B n=12 participants at risk Part B of the study
Gastrointestinal disorders Diarrhoea	77.8% 14/18 • Number of events 36 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	75.0% 9/12 • Number of events 14 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Fatigue	38.9% 7/18 • Number of events 9 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	66.7% 8/12 • Number of events 9 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Nausea	44.4% 8/18 • Number of events 9 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	66.7% 8/12 • Number of events 11 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Hyperglycaemia	55.6% 10/18 • Number of events 16 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	50.0% 6/12 • Number of events 8 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Dry skin	22.2% 4/18 • Number of events 4 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	41.7% 5/12 • Number of events 6 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Vomiting	27.8% 5/18 • Number of events 9 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	41.7% 5/12 • Number of events 7 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Rash maculo-papular	11.1% 2/18 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 4 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Pyrexia	11.1% 2/18 • Number of events 3 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	25.0% 3/12 • Number of events 3 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Respiratory tract infection	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	25.0% 3/12 • Number of events 3 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Blood and lymphatic system disorders Anaemia	22.2% 4/18 • Number of events 4 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 4 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Constipation	16.7% 3/18 • Number of events 3 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Decreased appetite	22.2% 4/18 • Number of events 4 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Dry mouth	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 2/18 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Nervous system disorders Headache	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Psychiatric disorders Insomnia	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Lower respiratory tract infection	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 3 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Rash macular	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Rhinitis	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Urinary tract infection	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 3 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	16.7% 2/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Rash	22.2% 4/18 • Number of events 4 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Hypokalaemia	16.7% 3/18 • Number of events 4 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Abdominal pain	11.1% 2/18 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Blood bilirubin increased	11.1% 2/18 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Electrocardiogram QT prolonged	11.1% 2/18 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	11.1% 2/18 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Oedema peripheral	11.1% 2/18 • Number of events 3 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Psychiatric disorders Anxiety	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Blood creatinine increased	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Catheter site erythema	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Catheter site infection	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Dehydration	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Nervous system disorders Dizziness	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Renal and urinary disorders Dysuria	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Feeling abnormal	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Vascular disorders Hypotension	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Lower respiratory tract infection viral	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Nasopharyngitis	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Non-cardiac chest pain	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Oral candidiasis	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Nervous system disorders Paraesthesia	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Vascular disorders Peripheral coldness	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Eye disorders Photophobia	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Skin infection	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Stomatitis	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Supropubic pain	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Troponin I increased	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Weight decreased	0.00% 0/18 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	8.3% 1/12 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Abdominal distension	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Dysphagia	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Glossitis	5.6% 1/18 • Number of events 2 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Mouth ulceration	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Oral pain	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Gastrointestinal disorders Proctalgia	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Application site pruritus	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
General disorders Peripheral swelling	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Infections and infestations Skin candida	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Injury, poisoning and procedural complications Joint injury	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Alanine aminotransferase increased	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Aspartate aminotransferase increased	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Blood alkaline phosphatase increased	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Blood creatinine decreased	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Blood lactate dehydrogenase increased	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Electrocardiogram T wave inversion	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Investigations Gamma-glutamyltransferase increased	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Hypoglycaemia	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Hypomagnesaemia	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Metabolism and nutrition disorders Hyponatraemia	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Musculoskeletal and connective tissue disorders Flank pain	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Musculoskeletal and connective tissue disorders Groin pain	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Renal and urinary disorders Pollakiuria	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Renal and urinary disorders Polyuria	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Nervous system disorders Migraine	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Nervous system disorders Restless legs syndrome	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Psychiatric disorders Depression	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Renal and urinary disorders Proteinuria	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Reproductive system and breast disorders Breast oedema	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Pruritus	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Skin and subcutaneous tissue disorders Rash pruritic	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Cardiac disorders Palpitations	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.
Endocrine disorders Hypothyroidism	5.6% 1/18 • Number of events 1 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.	0.00% 0/12 • Adverse events with an onset date on or after the date of first dose and up to and including 28 days following the date of last dose of study medication were collected.

Additional Information

Dr Justin P. O. Lindemann, MBChB MBA, Medical Science Director, AZD5363

AstraZeneca UK Limited

Phone: (0)7920 250301

Email: Justin.Lindemann@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place