Clinical Trial Results:
A Phase 2a, Randomised, Double-blind, Parallel Study to Assess the Efficacy, Safety and Tolerability of AZD9567 compared to Prednisolone 20 mg in patients with active Rheumatoid Arthritis (RA)
Summary
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EudraCT number |
2017-000838-64 |
Trial protocol |
NL DK |
Global end of trial date |
12 Nov 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Sep 2020
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First version publication date |
27 Sep 2020
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
D6470C00003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03368235 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
AstraZeneca
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Sponsor organisation address |
Karlebyhusentren, B674 Astraallen, Södertälje, Sweden, SE-151 85
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Public contact |
Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
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Scientific contact |
Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
06 Dec 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Nov 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Nov 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the efficacy of AZD9567 40 milligram (mg), compared to prednisolone 20 mg in participants with active rheumatoid arthritis (RA) in spite of stable treatment with conventional and/or subcutaneous or intravenous biological disease-modifying anti-rheumatic drugs (DMARDs).
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Protection of trial subjects |
This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice, applicable regulatory requirements and the AstraZeneca policy on Bioethics.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Jan 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 16
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Country: Number of subjects enrolled |
Sweden: 5
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Worldwide total number of subjects |
21
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EEA total number of subjects |
21
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
15
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
This was a Phase 2a study conducted in participants with active RA in spite of stable treatment with conventional DMARDs at 5 investigational sites across Sweden and The Netherlands between 18 January 2018 and 12 November 2019. | |||||||||
Pre-assignment
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Screening details |
A total of 21 participants were randomized in a 1:1 ratio to take either AZD9567 or prednisolone in a 2-week double-blind, double-dummy treatment period. | |||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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AZD9567 | |||||||||
Arm description |
Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo capsule matching with prednisolone orally once daily for 2 weeks.
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Investigational medicinal product name |
AZD9567
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
AZD9567 40 mg oral suspension once daily for 2 weeks.
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Arm title
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Prednisolone | |||||||||
Arm description |
Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Prednisolone 20 mg capsule orally once daily for 2 weeks.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo matching with AZD9567 oral suspension once daily for 2 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
AZD9567
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Reporting group description |
Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prednisolone
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Reporting group description |
Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
AZD9567
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Reporting group description |
Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks. | ||
Reporting group title |
Prednisolone
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Reporting group description |
Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks. |
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End point title |
Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at Day 15 | ||||||||||||
End point description |
The DAS28-CRP is a measure of disease activity in RA. The score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment (PGA) of health (ranging from very well to very poor). The DAS28-CRP was derived as follows: 0.56 x √[tender joint count 28 (TJC28)] + 0.28 x √[swollen joint count 28 (SJC28)] + 0.014 x global health (GH) + 0.36 x Ln(CRP+1) + 0.96 to produce the overall DAS28-CRP score on a scale ranged from 0-10 with higher score indicating worse RA symptoms. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The Full analysis set (FAS) included all participants who were randomized and received at least 1 dose of study treatment.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) and Day 15
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Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Statistical analysis description |
MMRM = mixed model repeated measures.
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Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.315 [1] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
0.472
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.487 | ||||||||||||
upper limit |
1.431 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.4569
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Notes [1] - Based on MMRM model with the baseline DAS28-CRP score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
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End point title |
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses | |||||||||||||||||||||
End point description |
The ACR20, ACR50 or ACR70 was achieved if there was at least a 20%, 50% or 70% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician’s global assessment of disease activity, participant's assessment of physical function and CRP. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment. Participants with missing ACR assessment at Day 15 were considered as non-responders in the respective analysis.
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End point type |
Secondary
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End point timeframe |
Day 15
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Statistical analysis title |
Treatment comparison ACR20:AZD9567 Vs prednisolone | |||||||||||||||||||||
Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.807 [2] | |||||||||||||||||||||
Method |
Regression, Logistic | |||||||||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||||||||
Point estimate |
0.807
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Confidence interval |
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level |
95% | |||||||||||||||||||||
sides |
2-sided
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lower limit |
0.12 | |||||||||||||||||||||
upper limit |
5.34 | |||||||||||||||||||||
Notes [2] - Logistic regression model with the treatment group, country and baseline DAS28-CRP as covariate. |
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Statistical analysis title |
Treatment comparison ACR70:AZD9567 Vs prednisolone | |||||||||||||||||||||
Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.183 | |||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||
Confidence interval |
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Statistical analysis title |
Treatment comparison ACR50:AZD9567 Vs prednisolone | |||||||||||||||||||||
Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||||||||
P-value |
= 0.198 | |||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||
Confidence interval |
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End point title |
LS Mean Change From Baseline in SJC66 Score at Day 15 | ||||||||||||
End point description |
A total of 66 joints (33 left, 33 right) were evaluated for swelling. The swollen joint count represents the number of joints in which there was synovial fluid and or soft tissue swelling, but not if bony overgrowth was found. A swollen joint was scored as 0 (absent) and 1 (present) for each joint. The SJC66 was calculated as sum of swollen joints with present status on electronic case report form (eCRF). The swollen joint count ranged from 0-66 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 15
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Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.717 [3] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
0.42
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.98 | ||||||||||||
upper limit |
2.81 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.136
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Notes [3] - The MMRM with the baseline SJC66 score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
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End point title |
LS Mean Change From Baseline in TJC68 Score at Day 15 | ||||||||||||
End point description |
A total of 68 joints (34 left, 34 right) were evaluated for tenderness. The tender joint count represents the number of joints in which pain was reported. A tender joint was scored as 0 (absent) and 1 (present) for each joint. The TJC68 was calculated as sum of tender joints with present status on eCRF. The tender joint count ranged from 0-68 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 15
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Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.724 [4] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
-1.12
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-7.69 | ||||||||||||
upper limit |
5.46 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
3.115
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Notes [4] - The MMRM with the baseline TJC68 score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
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End point title |
LS Mean Change From Baseline in TJC28 Score at Day 15 | ||||||||||||
End point description |
TJC28 was evaluated as one of the components that comprised the DAS28-score. A total of 28 joints (14 left, 14 right) were evaluated for tenderness as obtained from the joint count right or left eCRF. The tender joint count represents the number of joints in which pain was reported. A tender joint was scored as 0 (absent) and 1 (present) for each joint. The TJC28 was calculated as sum of tender joints with present status on eCRF. The tender joint count ranged from 0-28 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 15
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Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.973 [5] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
-0.05
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-3.43 | ||||||||||||
upper limit |
3.32 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.6
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Notes [5] - The MMRM with the baseline TJC28 score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
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End point title |
LS Mean Change From Baseline in SJC28 Score at Day 15 | ||||||||||||
End point description |
SJC28 was evaluated as one of the components that comprised the DAS28-score. A total of 28 joints (14 left, 14 right) were evaluated for swelling as obtained from the joint count right or left eCRF. The swollen joint count represents the number of joints in which there was synovial fluid and or soft tissue swelling, but not if bony overgrowth was found. A swollen joint was scored as 0 (absent) and 1 (present) for each joint. The SJC28 was calculated as sum of swollen joints with present status on eCRF. The swollen joint count ranged from 0-28 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 15
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Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.757 [6] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
0.26
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.5 | ||||||||||||
upper limit |
2.03 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.837
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Notes [6] - The MMRM with the baseline SJC28 score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
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End point title |
LS Mean Change From Baseline in GH Score at Day 15 | ||||||||||||
End point description |
GH was evaluated as one of the components that comprised the DAS28-score. Participant's GH was measured using PGA of disease activity by means of the visual analogue scale (VAS). The PGA VAS consists of a 100 millimeter (mm) long scale ranging from 0 (very well) to 100 (very poor). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 15
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Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.325 [7] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
9.8
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-10.5 | ||||||||||||
upper limit |
30.1 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
9.67
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Notes [7] - The MMRM with the baseline GH score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
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End point title |
LS Mean Change From Baseline in CRP at Day 15 | ||||||||||||
End point description |
CRP was evaluated as one of the components that comprised the DAS28-score. The CRP was collected at the local laboratory during screening and central laboratory on Days 1, 8, 15 and 28. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 15
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Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
|
||||||||||||
Number of subjects included in analysis |
21
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.187 [8] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
4.756
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.514 | ||||||||||||
upper limit |
12.025 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
3.4725
|
||||||||||||
Notes [8] - The MMRM with the baseline CRP score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
|
|||||||||||||
End point title |
LS Mean Change From Baseline in Participant's Assessment of Pain Score at Day 15 | ||||||||||||
End point description |
Participant's assessment of pain score was evaluated as one of the components that comprised the ACR. Participant's assessment of pain score was assessed from the amount of pain due to RA on a VAS ranging from 0 (no pain) to 100 (extreme pain). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 15
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
|
||||||||||||
Number of subjects included in analysis |
21
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.144 [9] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
16
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-6 | ||||||||||||
upper limit |
38.1 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
10.49
|
||||||||||||
Notes [9] - The MMRM with the baseline participant's assessment of pain score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
|
|||||||||||||
End point title |
LS Mean Change From Baseline in Physician’s Global Assessment of Disease Activity Score at Day 15 | ||||||||||||
End point description |
Physician's global assessment of disease activity score was evaluated as one of the components that comprised the ACR. The physician's global assessment of disease activity was measured on a VAS ranging from 0 (very well) to 100 (very poor). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 15
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
|
||||||||||||
Number of subjects included in analysis |
21
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.512 [10] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
3.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-8.3 | ||||||||||||
upper limit |
16 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
5.73
|
||||||||||||
Notes [10] - The MMRM with the baseline disease activity score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
|
|||||||||||||
End point title |
LS Mean Change From Baseline in Participant's Assessment of Physical Function Score at Day 15 | ||||||||||||
End point description |
Participant's assessment of physical function score was evaluated as one of the components that comprised the ACR. The participant's assessment of physical function across 8 functional areas was measured by health assessment questionnaire. The total score ranging from 0 (no difficulty) to 24 (inability to perform tasks). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. The FAS included all participants who were randomized and received at least 1 dose of study treatment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 15
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment comparison: AZD9567 Vs prednisolone | ||||||||||||
Comparison groups |
AZD9567 v Prednisolone
|
||||||||||||
Number of subjects included in analysis |
21
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.589 [11] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS mean difference | ||||||||||||
Point estimate |
0.131
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.37 | ||||||||||||
upper limit |
0.631 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.2381
|
||||||||||||
Notes [11] - The MMRM with the baseline physical function score as a continuous covariate and country, visit and treatment group as categorical fixed effects, as well as visit interaction with treatment group, using unstructured covariance matrix. |
|
|||||||||
End point title |
Area Under the Plasma Concentration-Time Curve Until the Last Quantifiable Concentration (AUClast) of AZD9567 [12] | ||||||||
End point description |
The AUClast was determined using non-compartmental method and calculated using the linear trapezoidal rule when concentrations were increased and the logarithmic trapezoidal rule when concentrations were decreased. The Pharmacokinetic (PK) analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
|
||||||||
Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was only assessed in participants randomized to AZD9567 reporting group. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Area Under the Concentration-Time Curve From Time Zero to 6 Hours After Dose (AUC0-6) of AZD9567 [13] | ||||||||
End point description |
The AUC0-6 was determined using non-compartmental method and calculated using the linear trapezoidal rule when concentrations were increased and the logarithmic trapezoidal rule when concentrations were decreased. The PK analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
|
||||||||
Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was only assessed in participants randomized to AZD9567 reporting group. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Maximum Observed Plasma Concentration (Cmax) of AZD9567 [14] | ||||||||
End point description |
The Cmax of AZD9567 was determined using non-compartmental method. The PK analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
|
||||||||
Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was only assessed in participants randomized to AZD9567 reporting group. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Time to Reach Maximum Plasma Concentration (tmax) of AZD9567 [15] | ||||||||
End point description |
The tmax of AZD9567 was determined using non-compartmental method. The PK analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
|
||||||||
Notes [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was only assessed in participants randomized to AZD9567 reporting group. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Last Plasma Concentration Measured Before the Last Dose (Ctrough) of AZD9567 [16] | ||||||||
End point description |
The Ctrough of AZD9567 was determined using non-compartmental method before the last dose on Day 15. The PK analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history. 99999 = not calculable due to a zero predose value.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose on Day 15
|
||||||||
Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was only assessed in participants randomized to AZD9567 reporting group. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first administration of study treatment (Day 1) up to 2 weeks after last administration of study treatment, approximately 28 days.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The Safety analysis set included all participants who were randomized and received at least 1 dose of study treatment.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AZD9567
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prednisolone
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
04 Oct 2017 |
Modification of AZD9567 dose from 80 to 40 mg. |
||
19 Mar 2019 |
Increase in number of sites from 4-6 to maximum of 10. Addition of erythrocyte sedimentation rate under laboratory (hematology) assessments. Amendment of Appendix D “Actions Required in Cases of Increases in Liver Biochemistry and Evaluation of Hy´s Law” to implement the new reporting process regarding potential Hy's law. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |