A Single Ascending Dose Study To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of AZD9567.

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• Arthritis 3,554
• Arthritis, Rheumatoid 2,888

Keywords

• AZD9567
• Healthy subjects
• Phase 1
• placebo controlled
• single ascending dose
• Pharmacokinetics
• Pharmacodynamics
• Rheumatoid Arthritis

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 72 is below the median of 90 across 2,377 interventional studies indexed under Arthritis.

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Study arms

• Experimental
  AZD9567 oral suspension

  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 comparator
  Placebo

  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

• Experimental
  Prednisolone capsules

  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

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).

Primary outcomes

1. 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)

2. 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)

3. 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)

4. 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)

5. 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)

6. 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)

Secondary outcomes

1. 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)

2. 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)

3. 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)

Baseline characteristics