Healthy Subjects, Pharmacodynamics, Pharmacokinetics, Rheumatoid Arthritis, Safety, Tolerability
Conditions
Keywords
AZD9567, Healthy subjects, Phase 1, placebo controlled, single ascending dose, Pharmacokinetics, Pharmacodynamics, Rheumatoid Arthritis
Brief summary
This is a Phase I, first-in-human (FIH), randomized, single-blind, placebo-controlled, single ascending dose sequential group study in healthy male subjects. The objectives are to study the safety, tolerability, pharmacokinetics and effects on glucose homeostasis (pharmacodynamics) of AZD9567, an oral differentiated non-steroidal selective glucocorticoid receptor modulator (SGRM). The study will also assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of prednisolone 60 mg in comparison with high doses of AZD9567 and placebo.
Detailed description
This is a Phase I, first-in-human (FIH), randomized, single-blind, placebo-controlled, single ascending dose sequential group study in healthy male subjects. The objectives are to study the safety, tolerability, pharmacokinetics and effects on glucose homeostasis (pharmacodynamics) of AZD9567. Additional exploratory variables (Inflammation biomarkers, ECG modelling and taste assessment) will also be evaluated. The study will also assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of prednisolone 60 mg in comparison with high doses of AZD9567 and placebo. The study will be conducted at a single study centre with a planned number of subjects of up to 72 healthy males, aged 18 to 55 years.
Interventions
DRUGAZD9567 Monohydrat
AZD9567 oral suspension 0.5 to 10 mg/ml
DRUGPlacebo oral suspension/ Placebo capsule
Matching placebo
DRUGPrednisolone
Prednisolone 60mg oral capsules (12 capsules of 5 mg each).
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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) | 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. |
| Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 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) | 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. |
| Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 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) | 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. |
| 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)) | 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) | 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. |
| Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | 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) | 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. |
| Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake) | 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. |
| Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake) | 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. |
| Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake) | 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. |
Countries
Germany
Participant flow
Recruitment details
Phase 1, single-center (Berlin), randomized, single-blind, placebo-controlled study carried on 72 healthy male participants (8 subjects per cohort). In Cohort 1-8, participants were randomized to AZD9567:placebo (6:2). In Cohort 9, participants were randomized to prednisolone:placebo (6:2). Participants received treatment in a fasted state
Pre-assignment details
Screening period (Day -28 to Day -3). For Cohort 7, screening period was up to 21 days
Participants by arm
| Arm | Count |
|---|---|
| AZD9567 - 2 mg In Cohort 1, participants received single dose of AZD8567 2 mg oral suspension in the fasted state | 6 |
| AZD9567 - 10 mg In Cohort 2, participants received single dose of AZD8567 10 mg oral suspension in the fasted state | 6 |
| AZD9567 - 20 mg In Cohort 3, participants received single dose of AZD8567 20 mg oral suspension in the fasted state | 6 |
| AZD9567 - 40 mg In Cohort 4, participants received single dose of AZD8567 40 mg oral suspension in the fasted state | 6 |
| AZD9567 - 80 mg In Cohort 5, participants received single dose of AZD8567 80 mg oral suspension in the fasted state | 6 |
| AZD9567 - 100 mg In Cohort 6, participants received single dose of AZD8567 100 mg oral suspension in the fasted state | 6 |
| AZD9567 - 125 mg In Cohort 7, participants received single dose of AZD8567 125 mg oral suspension in the fasted state | 6 |
| AZD9567 - 155 mg In Cohort 8, participants received single dose of AZD8567 155 mg oral suspension in the fasted state | 6 |
| Prednisolone - 60 mg In Cohort 9, participants received orally single dose of prednisolone 60 mg capsule in the fasted state | 6 |
| 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 |
| Total | 72 |
Baseline characteristics
| Characteristic | Pooled Placebo | Total | AZD9567 - 2 mg | AZD9567 - 10 mg | AZD9567 - 20 mg | AZD9567 - 40 mg | AZD9567 - 80 mg | AZD9567 - 100 mg | AZD9567 - 125 mg | AZD9567 - 155 mg | Prednisolone - 60 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Cohort 1-8 AZD9567 | 0 Years STANDARD_DEVIATION 0 | 37 Years STANDARD_DEVIATION 10 | 44 Years STANDARD_DEVIATION 10 | 35 Years STANDARD_DEVIATION 14 | 35 Years STANDARD_DEVIATION 8 | 35 Years STANDARD_DEVIATION 9 | 38 Years STANDARD_DEVIATION 12 | 34 Years STANDARD_DEVIATION 9 | 41 Years STANDARD_DEVIATION 8 | 32 Years STANDARD_DEVIATION 8 | 0 Years STANDARD_DEVIATION 0 |
| Age, Continuous Cohort 9 Prenisolone | 0 Years STANDARD_DEVIATION 0 | 36 Years STANDARD_DEVIATION 9 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 36 Years STANDARD_DEVIATION 9 |
| Age, Continuous Pooled Placebo | 37 Years STANDARD_DEVIATION 11 | 37 Years STANDARD_DEVIATION 11 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 | 0 Years STANDARD_DEVIATION 0 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 18 Participants | 72 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 2 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 3 / 18 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 18 |
Outcome results
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 - 2 mg | 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) | 1007 h*nmol/L | Geometric Coefficient of Variation 38.22 |
| AZD9567 - 10 mg | 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) | 5266 h*nmol/L | Geometric Coefficient of Variation 42.57 |
| AZD9567 - 20 mg | 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) | 7670 h*nmol/L | Geometric Coefficient of Variation 28.26 |
| AZD9567 - 40 mg | 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) | 14000 h*nmol/L | Geometric Coefficient of Variation 62.53 |
| AZD9567 - 80 mg | 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) | 31840 h*nmol/L | Geometric Coefficient of Variation 34.55 |
| AZD9567 - 100 mg | 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) | 42080 h*nmol/L | Geometric Coefficient of Variation 27.83 |
| AZD9567 - 125 mg | 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) | 41290 h*nmol/L | Geometric Coefficient of Variation 14.63 |
| AZD9567 - 155 mg | 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) | 57500 h*nmol/L | Geometric Coefficient of Variation 37.51 |
90% CI: [0.856, 0.978]
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 - 2 mg | 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)) | 940.6 h*nmol/L | Geometric Coefficient of Variation 40.32 |
| AZD9567 - 10 mg | 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)) | 5069 h*nmol/L | Geometric Coefficient of Variation 41.83 |
| AZD9567 - 20 mg | 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)) | 7598 h*nmol/L | Geometric Coefficient of Variation 28.12 |
| AZD9567 - 40 mg | 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)) | 13860 h*nmol/L | Geometric Coefficient of Variation 62.81 |
| AZD9567 - 80 mg | 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)) | 31600 h*nmol/L | Geometric Coefficient of Variation 34.57 |
| AZD9567 - 100 mg | 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)) | 41850 h*nmol/L | Geometric Coefficient of Variation 27.82 |
| AZD9567 - 125 mg | 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)) | 40930 h*nmol/L | Geometric Coefficient of Variation 14.32 |
| AZD9567 - 155 mg | 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)) | 56940 h*nmol/L | Geometric Coefficient of Variation 36.8 |
90% CI: [0.869, 0.991]
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 - 2 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 184.9 nmol/L | Geometric Coefficient of Variation 20.18 |
| AZD9567 - 10 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 751.6 nmol/L | Geometric Coefficient of Variation 25.03 |
| AZD9567 - 20 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 1327 nmol/L | Geometric Coefficient of Variation 17.28 |
| AZD9567 - 40 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 2536 nmol/L | Geometric Coefficient of Variation 38.33 |
| AZD9567 - 80 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 4261 nmol/L | Geometric Coefficient of Variation 13.88 |
| AZD9567 - 100 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 5835 nmol/L | Geometric Coefficient of Variation 14.14 |
| AZD9567 - 125 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 6080 nmol/L | Geometric Coefficient of Variation 21.3 |
| AZD9567 - 155 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax) | 6900 nmol/L | Geometric Coefficient of Variation 33.97 |
90% CI: [0.807, 0.887]
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 - 2 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 4.716 Hours | Standard Deviation 0.8182 |
| AZD9567 - 10 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 5.444 Hours | Standard Deviation 2.157 |
| AZD9567 - 20 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 3.929 Hours | Standard Deviation 1.237 |
| AZD9567 - 40 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 4.199 Hours | Standard Deviation 1.417 |
| AZD9567 - 80 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 5.286 Hours | Standard Deviation 1.469 |
| AZD9567 - 100 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 5.297 Hours | Standard Deviation 1.041 |
| AZD9567 - 125 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 4.664 Hours | Standard Deviation 1.052 |
| AZD9567 - 155 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz) | 6.449 Hours | Standard Deviation 1.778 |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| AZD9567 - 2 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 0.50 Hours | Full Range 20.18 |
| AZD9567 - 10 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 0.75 Hours | Full Range 25.03 |
| AZD9567 - 20 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 0.51 Hours | Full Range 17.28 |
| AZD9567 - 40 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 0.75 Hours | Full Range 38.33 |
| AZD9567 - 80 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 1.00 Hours | Full Range 13.88 |
| AZD9567 - 100 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 1.00 Hours | Full Range 14.14 |
| AZD9567 - 125 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 1.00 Hours | Full Range 21.3 |
| AZD9567 - 155 mg | Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax) | 1.25 Hours | Full Range 33.97 |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD9567 - 2 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| AZD9567 - 2 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| AZD9567 - 2 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| AZD9567 - 2 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 0 Participants |
| AZD9567 - 10 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| AZD9567 - 10 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 0 Participants |
| AZD9567 - 10 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| AZD9567 - 10 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| AZD9567 - 20 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 1 Participants |
| AZD9567 - 20 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| AZD9567 - 20 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| AZD9567 - 20 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| AZD9567 - 40 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| AZD9567 - 40 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| AZD9567 - 40 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 0 Participants |
| AZD9567 - 40 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| AZD9567 - 80 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 0 Participants |
| AZD9567 - 80 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| AZD9567 - 80 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| AZD9567 - 80 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| AZD9567 - 100 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 2 Participants |
| AZD9567 - 100 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| AZD9567 - 100 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| AZD9567 - 100 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| AZD9567 - 125 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 1 Participants |
| AZD9567 - 125 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| AZD9567 - 125 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| AZD9567 - 125 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| AZD9567 - 155 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| AZD9567 - 155 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 0 Participants |
| AZD9567 - 155 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| AZD9567 - 155 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| Prednisolone - 60 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 0 Participants |
| Prednisolone - 60 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
| Prednisolone - 60 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| Prednisolone - 60 mg | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| Pooled Placebo | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any serious adverse event (SAE) (including death) | 0 Participants |
| Pooled Placebo | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE | 3 Participants |
| Pooled Placebo | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE (including events with outcome =death) | 0 Participants |
| Pooled Placebo | Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events | Any AE leading to discontinuation of AZD9567 | 0 Participants |
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.
Time frame: At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD9567 - 2 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.06 min*nmol/L |
| AZD9567 - 10 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.04 min*nmol/L |
| AZD9567 - 20 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.02 min*nmol/L |
| AZD9567 - 40 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 0.933 min*nmol/L |
| AZD9567 - 80 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 0.919 min*nmol/L |
| AZD9567 - 100 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.00 min*nmol/L |
| AZD9567 - 125 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 0.983 min*nmol/L |
| AZD9567 - 155 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 0.968 min*nmol/L |
| Prednisolone - 60 mg | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 0.749 min*nmol/L |
| Pooled Placebo | Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.08 min*nmol/L |
90% CI: [0.861, 1.12]
90% CI: [0.846, 1.09]
90% CI: [0.829, 1.07]
90% CI: [0.757, 0.979]
90% CI: [0.745, 0.964]
90% CI: [0.815, 1.05]
90% CI: [0.798, 1.03]
90% CI: [0.784, 1.02]
90% CI: [0.608, 0.785]
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.
Time frame: At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD9567 - 2 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.19 min*pmol/L |
| AZD9567 - 10 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.20 min*pmol/L |
| AZD9567 - 20 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.03 min*pmol/L |
| AZD9567 - 40 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.04 min*pmol/L |
| AZD9567 - 80 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 0.999 min*pmol/L |
| AZD9567 - 100 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 0.980 min*pmol/L |
| AZD9567 - 125 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.15 min*pmol/L |
| AZD9567 - 155 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.16 min*pmol/L |
| Prednisolone - 60 mg | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 0.784 min*pmol/L |
| Pooled Placebo | Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.14 min*pmol/L |
90% CI: [0.872, 1.26]
90% CI: [0.874, 1.26]
90% CI: [0.745, 1.1]
90% CI: [0.762, 1.1]
90% CI: [0.728, 1.05]
90% CI: [0.716, 1.03]
90% CI: [0.842, 1.21]
90% CI: [0.846, 1.22]
90% CI: [0.572, 0.825]
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.
Time frame: At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD9567 - 2 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.04 min*mmol/L |
| AZD9567 - 10 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.01 min*mmol/L |
| AZD9567 - 20 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.07 min*mmol/L |
| AZD9567 - 40 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.06 min*mmol/L |
| AZD9567 - 80 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.08 min*mmol/L |
| AZD9567 - 100 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.17 min*mmol/L |
| AZD9567 - 125 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.16 min*mmol/L |
| AZD9567 - 155 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.20 min*mmol/L |
| Prednisolone - 60 mg | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.19 min*mmol/L |
| Pooled Placebo | Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT]) | 1.01 min*mmol/L |
90% CI: [0.96, 1.11]
90% CI: [0.929, 1.08]
90% CI: [0.987, 1.14]
95% CI: [0.983, 1.13]
90% CI: [0.995, 1.15]
90% CI: [1.09, 1.25]
90% CI: [1.07, 1.24]
90% CI: [1.11, 1.29]
90% CI: [1.11, 1.27]