A Single Ascending Dose Study To Assess The Safety, Toler... | NCT02512575

ID	Type	Description	Link
2015-002002-37	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
AZD9567 oral suspension	Experimental	In Part A: up to 8 cohorts with single ascending doses (starting at 2 mg up to 155 mg). In Part B: one cohort with a single dose	Drug: AZD9567 Monohydrat
Placebo	Placebo Comparator	Subjects randomized to placebo in the first 8 cohorts will receive the same dose volume of oral suspension as subjects on AZD9567 and subjects randomized to placebo in cohort 9(prednisolone cohort) will receive the same number of capsules as subjects on prednisolone.	Drug: Placebo oral suspension/ Placebo capsule
Prednisolone capsules	Experimental	Within each cohort 6 subjects will be randomized to receive prednisolone 60mg oral capsules and 2 subjects randomized to receive matching placebo in a fasted state. Sentinel dosing will not be employed for the prednisolone cohort. The SRC will not be required to evaluate the prednisolone cohort. This cohort can be performed at any time during clinical execution of the study provided the protocol amendment was approved.	Drug: Prednisolone

Name	Type	Description	Arm Group Labels	Other Names
AZD9567 Monohydrat	Drug	AZD9567 oral suspension 0.5 to 10 mg/ml	AZD9567 oral suspension

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events	Safety and tolerability variables included AEs, vital signs (blood pressure and pulse), ECGs (12-lead ECGs, safety ECGs and telemetry), clinical laboratory safety evaluations (haematology, clinical chemistry [including osteocalcin], coagulation, urinalysis [including 24 hour urine cortisol per day {tU-cortisol}]) and physical examinations. Note: No clinically relevant findings were noted in clinical laboratory results and vial signs assessments. Hence, none of the laboratory or vital signs findings were reported as AEs.	At screening, Day -2, Day -1, Day 1 (at pre-dose; 3 & 12 hours post-dose), Day 2 (24 hours post-dose), Day 3 and follow-up (7 to 10 days post-dose)
Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax)	To assess the Cmax of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state. Cmax was taken directly from the individual concentration-time curve.	On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax)	To assess the tmax of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state. tmax was taken directly from the individual concentration-time curve.	On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz)	To assess t½λz of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state. t½λz was estimated as (ln2)/λz.

Secondary Outcomes

Measure	Description	Time Frame
Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT])	To assess the effect of AZD9567 and prednisolone on OGTT after administration of 75 g glucose solution, blood samples were collected pre glucose intake and at post glucose intake for the analyses of plasma glucose. AUC0-4h relative change between Day 1 and Day -1 was calculated for each subject in a specific treatment group. Note: Total AUC0-4h was calculated using the linear trapezoidal method. Statistical analysis for the change in OGTT plasma glucose total AUC0-4h values were assessed via an analysis of variance (ANCOVA), with treatment as fixed effect.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provision of signed and dated, written informed consent prior to any study specific procedures.
Healthy male subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
Have a body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
Normal OGTT at screening (<7.8 mmol/L).
Serum cortisol levels within normal limits at screening (collected as part of the clinical chemistry panel).
Able to understand, read and speak the German language.

Exclusion Criteria:

History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
History of or active or latent tuberculosis (TB), or at risk for having acquired TB (social workers or prison staff in countries with endemic rates of TB, having lived with patients with known TB).
History suggesting abnormal immune function, as judged by the investigator.
Any contraindications to be treated with prednisolone (allergy to any ingredient, systemic fungal infection, certain type of malaria, inflammation of the optic nerve, or herpes infection of the eye, scheduled to have a live or attenuated live vaccination or taking mifepristone).
History of severe affective disorder including depressive or manic-depressive illness them self or first degree relatives.
History of previous steroid psychosis
Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
Any latent or chronic infections (e.g., recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (surgery, trauma, or significant infection), or history of skin abscesses within 90 days prior to the first administration of IMP.
Any clinically important laboratory abnormalities (clinical chemistry, hematology, coagulation or urinalysis results), as judged by the investigator. In particular a subject with an abnormal value in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), creatinine, thyroid-stimulating hormone (TSH), fasting glucose, International Normalised Ratio (INR), haemoglobin (Hb), white blood cell (WBC), absolute neutrophil or platelet count will be excluded.
Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV).
Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: Systolic BP (SBP) < 90mmHg or ≥ 140 mmHg, Diastolic BP (DBP) < 50mmHg or ≥ 90 mmHg, Pulse < 45 or > 85 beats per minute (bpm).
Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
Prolonged QTcF > 450 ms or family history of long QT syndrome.
PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation).
PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation

Name	Affiliation	Role
Rainhard Fuhr, Dr. med.	PAREXEL International GmbH, Berlin	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Berlin		14050	Germany

PubMed Identifier	Type	Citation	Retractions
38258274	Derived	Hegelund Myrback T, Prothon S, Edman K, Leander J, Hashemi M, Dearman M, Edenro G, Svanberg P, Andersson EM, Almquist J, Ammala C, Hendrickx R, Taib Z, Johansson KA, Berggren AR, Keen CM, Eriksson UG, Fuhr R, Carlsson BCL. Effects of a selective glucocorticoid receptor modulator (AZD9567) versus prednisolone in healthy volunteers: two phase 1, single-blind, randomised controlled trials. Lancet Rheumatol. 2020 Jan;2(1):e31-e41. doi: 10.1016/S2665-9913(19)30103-1. Epub 2019 Dec 9.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
FG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
BG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state
BG002	AZD9567 - 20 mg	In Cohort 3, participants received single dose of AZD8567 20 mg oral suspension in the fasted state
BG003	AZD9567 - 40 mg	In Cohort 4, participants received single dose of AZD8567 40 mg oral suspension in the fasted state
BG004	AZD9567 - 80 mg	In Cohort 5, participants received single dose of AZD8567 80 mg oral suspension in the fasted state
BG005	AZD9567 - 100 mg	In Cohort 6, participants received single dose of AZD8567 100 mg oral suspension in the fasted state
BG006	AZD9567 - 125 mg	In Cohort 7, participants received single dose of AZD8567 125 mg oral suspension in the fasted state
BG007	AZD9567 - 155 mg	In Cohort 8, participants received single dose of AZD8567 155 mg oral suspension in the fasted state
BG008	Prednisolone - 60 mg	In Cohort 9, participants received orally single dose of prednisolone 60 mg capsule in the fasted state
BG009	Pooled Placebo	In Cohort 1-8, participants were randomized to AZD9567:placebo (6:2). In Cohort 9, participants were randomized to prednisolone:placebo (6:2)
BG010	Total	Total of all reporting groups

Units	Counts
Participants	BG0006 BG0016 BG0026 BG0036 BG0046 BG0056 BG0066 BG0076 BG0086 BG00918 BG01072

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events

Safety and tolerability variables included AEs, vital signs (blood pressure and pulse), ECGs (12-lead ECGs, safety ECGs and telemetry), clinical laboratory safety evaluations (haematology, clinical chemistry [including osteocalcin], coagulation, urinalysis [including 24 hour urine cortisol per day {tU-cortisol}]) and physical examinations.

Note: No clinically relevant findings were noted in clinical laboratory results and vial signs assessments. Hence, none of the laboratory or vital signs findings were reported as AEs.

All participants who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study. IMP includes AZD9567, Prednisolone 60 mg and placebo.

Posted

Number

Participants

At screening, Day -2, Day -1, Day 1 (at pre-dose; 3 & 12 hours post-dose), Day 2 (24 hours post-dose), Day 3 and follow-up (7 to 10 days post-dose)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state
OG002	AZD9567 - 20 mg	In Cohort 3, participants received single dose of AZD8567 20 mg oral suspension in the fasted state
OG003	AZD9567 - 40 mg	In Cohort 4, participants received single dose of AZD8567 40 mg oral suspension in the fasted state
OG004	AZD9567 - 80 mg	In Cohort 5, participants received single dose of AZD8567 80 mg oral suspension in the fasted state
OG005	AZD9567 - 100 mg	In Cohort 6, participants received single dose of AZD8567 100 mg oral suspension in the fasted state
OG006	AZD9567 - 125 mg	In Cohort 7, participants received single dose of AZD8567 125 mg oral suspension in the fasted state
OG007	AZD9567 - 155 mg	In Cohort 8, participants received single dose of AZD8567 155 mg oral suspension in the fasted state
OG008	Prednisolone - 60 mg	In Cohort 9, participants received orally single dose of prednisolone 60 mg capsule in the fasted state
OG009	Pooled Placebo	In Cohort 1-8, participants were randomized to AZD9567:placebo (6:2). In Cohort 9, participants were randomized to prednisolone:placebo (6:2)

Units	Counts
Participants	OG0006 OG0016 OG0026 OG003

Title

Denominators

Categories

Any AE

Title	Measurements
	OG0000 OG0010 OG0021 OG003

Primary

Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax)

To assess the Cmax of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state. Cmax was taken directly from the individual concentration-time curve.

The pharmacokinetic (PK) analysis set consisted of all participants in the safety analysis set who received a dose of AZD9567 and had at least one of the parameters Cmax, AUC / AUC(0-last) evaluable. All protocol deviations were considered for the severity/impact and were accounted when participants were assigned to the PK analysis sets.

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol/L

On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state
OG002	AZD9567 - 20 mg

Primary

Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax)

To assess the tmax of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state. tmax was taken directly from the individual concentration-time curve.

The PK analysis set consisted of all participants in the safety analysis set who received a dose of AZD9567 and had at least one of the parameters Cmax, AUC / AUC(0-last) evaluable. All protocol deviations were considered for the severity/impact and were accounted when participants were assigned to the PK analysis sets.

Posted

Median

Full Range

Hours

On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state
OG002	AZD9567 - 20 mg	In Cohort 3, participants received single dose of AZD8567 20 mg oral suspension in the fasted state

Primary

Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz)

To assess t½λz of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state. t½λz was estimated as (ln2)/λz.

Posted

Mean

Standard Deviation

Hours

On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state
OG002	AZD9567 - 20 mg	In Cohort 3, participants received single dose of AZD8567 20 mg oral suspension in the fasted state

Primary

Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUC(0-last))

To assess AUC(0-last) of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*nmol/L

On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state
OG002	AZD9567 - 20 mg

Primary

Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC)

To assess AUC of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state. AUC was estimated by AUC(0-last) + Clast/λz. Clast - the last observed quantifiable concentration.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*nmol/L

On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state
OG002	AZD9567 - 20 mg

Secondary

Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT])

To assess the effect of AZD9567 and prednisolone on OGTT after administration of 75 g glucose solution, blood samples were collected pre glucose intake and at post glucose intake for the analyses of plasma glucose. AUC0-4h relative change between Day 1 and Day -1 was calculated for each subject in a specific treatment group.

Note: Total AUC0-4h was calculated using the linear trapezoidal method. Statistical analysis for the change in OGTT plasma glucose total AUC0-4h values were assessed via an analysis of variance (ANCOVA), with treatment as fixed effect.

The pharmacodynamics (PD) analysis set consisted of all participants who received a dose of AZD9567/placebo and who had at least one pre-dose and one post-dose measurement for one of plasma glucose, insulin and C-peptide, and who had no major protocol deviations thought to have impacted the analysis of the PD data.

Posted

Geometric Mean

95% Confidence Interval

min*mmol/L

At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state

Secondary

Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT])

To assess the effect of AZD9567 and prednisolone on OGTT after administration of 75 g glucose solution, blood samples were collected pre glucose intake and at post glucose intake for the analyses of serum insulin. AUC0-4h relative change between Day 1 and Day -1 was calculated for each subject in a specific treatment group.

Note: Total AUC0-4h was calculated using the linear trapezoidal method. Statistical analysis for the change in OGTT serum insulin total AUC0-4h values were assessed via an analysis of variance (ANCOVA), with treatment as fixed effect.

The PD analysis set consisted of all participants who received a dose of AZD9567/placebo and who had at least one pre-dose and one post-dose measurement for one of plasma glucose, insulin and C-peptide, and who had no major protocol deviations thought to have impacted the analysis of the PD data.

Posted

Geometric Mean

95% Confidence Interval

min*pmol/L

At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state

Secondary

Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT])

To assess the effect of AZD9567 and prednisolone on OGTT after administration of 75 g glucose solution, blood samples were collected pre glucose intake and at post glucose intake for the analyses of serum C-peptide. AUC0-4h relative change between Day 1 and Day -1 was calculated for each subject in a specific treatment group.

Note: Total AUC0-4h was calculated using the linear trapezoidal method. Statistical analysis for the change in OGTT serum C-peptide total AUC0-4h values were assessed via an analysis of variance (ANCOVA), with treatment as fixed effect.

Posted

Geometric Mean

95% Confidence Interval

min*nmol/L

At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)

ID	Title	Description
OG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state
OG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AZD9567 - 2 mg	In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state	6	0	6
EG001	AZD9567 - 10 mg	In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state	6	0	6
EG002	AZD9567 - 20 mg	In Cohort 3, participants received single dose of AZD8567 20 mg oral suspension in the fasted state	6	1	6
EG003	AZD9567 - 40 mg	In Cohort 4, participants received single dose of AZD8567 40 mg oral suspension in the fasted state	6	0	6
EG004	AZD9567 - 80 mg	In Cohort 5, participants received single dose of AZD8567 80 mg oral suspension in the fasted state	6	0	6
EG005	AZD9567 - 100 mg	In Cohort 6, participants received single dose of AZD8567 100 mg oral suspension in the fasted state	6	2	6
EG006	AZD9567 - 125 mg	In Cohort 7, participants received single dose of AZD8567 125 mg oral suspension in the fasted state	6	1	6
EG007	AZD9567 - 155 mg	In Cohort 8, participants received single dose of AZD8567 155 mg oral suspension in the fasted state	6	0	6
EG008	Prednisolone - 60 mg	In Cohort 9, participants received orally single dose of prednisolone 60 mg capsule in the fasted state	6	0	6
EG009	Pooled Placebo	In Cohort 1-8, participants were randomized to AZD9567:placebo (6:2). In Cohort 9, participants were randomized to prednisolone:placebo (6:2)	18	3	18

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest pain	General disorders	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG0030 affected6 at risk EG0040 affected6 at risk EG0050 affected6 at risk EG0060 affected6 at risk EG0070 affected6 at risk EG0080 affected6 at risk EG0090 affected18 at risk
Feeling hot	General disorders	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Vessel puncture site pain	General disorders	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Oral herpes	Infections and infestations	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Hot flush	Vascular disorders	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA version 18.1.	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds