Trial Outcomes & Findings for AZD2423 Safety and Tolerability Study in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease(COPD) (NCT NCT01215279)
NCT ID: NCT01215279
Last Updated: 2014-10-23
Results Overview
Number of all participants with clinically significant changes in laboratory variables, except monocyte, assessed at all the listed time points
COMPLETED
PHASE2
63 participants
Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)
2014-10-23
Participant Flow
This study was conducted at 11 centres in 2 countries: 5 in Bulgaria and 6 in Slovakia. The first patient was enrolled on 09 October 2010 and the last patient last visit was on 08 March 2011.
Participant milestones
| Measure |
AZD2423 100 mg
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
32
|
|
Overall Study
COMPLETED
|
31
|
32
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
AZD2423 Safety and Tolerability Study in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease(COPD)
Baseline characteristics by cohort
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
Total
n=63 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.5 Years
STANDARD_DEVIATION 7.8 • n=99 Participants
|
60.6 Years
STANDARD_DEVIATION 7.2 • n=107 Participants
|
61.6 Years
STANDARD_DEVIATION 7.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
47 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)Number of all participants with clinically significant changes in laboratory variables, except monocyte, assessed at all the listed time points
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes in Laboratory Variables Other Than Monocytes
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)Number of participants with clinically significant changes in vital signs assessed at all the listed time points
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes in Vital Signs
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)Number of participants with clinically significant changes in ECG variables assessed at all the listed time points
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes in ECG Variables
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1, 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks (follow-up)Number of participants with clinically significant changes in physical examination assessed at all the listed time points
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Number of Participants With Clinically Significant Changes in Physical Examination
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1Monocyte count in peripheral blood at baseline (Pre-dose, Day 1)
Outcome measures
| Measure |
AZD2423 100 mg
n=30 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=28 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Monocytes at Baseline
|
0.47 10^9/L
Standard Deviation 0.136
|
0.43 10^9/L
Standard Deviation 0.143
|
PRIMARY outcome
Timeframe: week 4Monocyte count in peripheral blood at end of treatment (4 weeks)
Outcome measures
| Measure |
AZD2423 100 mg
n=27 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=29 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Monocytes at End of Treatment
|
0.43 10^9/L
Standard Deviation 0.165
|
0.55 10^9/L
Standard Deviation 0.178
|
PRIMARY outcome
Timeframe: week 5 (follow-up)Monocyte count in peripheral blood at follow-up (Week 5; 1 week after end of treatment)
Outcome measures
| Measure |
AZD2423 100 mg
n=27 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=29 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Monocytes at Follow-up
|
0.50 10^9/L
Standard Deviation 0.175
|
0.52 10^9/L
Standard Deviation 0.196
|
SECONDARY outcome
Timeframe: Average of 10 days of pre-treatment measurements (day -10 to -1)Measurements conducted by patient in morning upon rising, before intake of morning dose of investigational product but after clearing out mucus. Patients was to refrain from taking rescue medication prior to measurement if possible.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Morning FEV1 at Baseline
|
1.3 L
Standard Deviation 0.41
|
1.3 L
Standard Deviation 0.44
|
SECONDARY outcome
Timeframe: Average of the last 7 days of treatment (week 4)Measurements conducted by patient in morning upon rising, before intake of morning dose of investigational product but after clearing out mucus. Patients was to refrain from taking rescue medication prior to measurement if possible.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Morning FEV1 During Last 7 Days of Treatment
|
1.3 L
Standard Deviation 0.40
|
1.4 L
Standard Deviation 0.52
|
SECONDARY outcome
Timeframe: Average of 10 days of pre-treatment measurements (day -10 to -1)Measurement conducted by patient in evening.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Evening FEV1 at Baseline
|
1.3 L
Standard Deviation 0.43
|
1.4 L
Standard Deviation 0.44
|
SECONDARY outcome
Timeframe: Average of the last 7 days of treatment (week 4)Measurement conducted by patient in evening.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Evening FEV1 During Last 7 Days of Treatment
|
1.2 L
Standard Deviation 0.37
|
1.4 L
Standard Deviation 0.51
|
SECONDARY outcome
Timeframe: Average of 10 days of pre-treatment measurements (day -10 to -1)Measurements conducted by patient in morning upon rising, before intake of morning dose of investigational product but after clearing out mucus. Patients was to refrain from taking rescue medication prior to measurement if possible.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Morning Peak Expiratory Flow (PEF) at Baseline
|
190.5 L/minute
Standard Deviation 74.73
|
185.5 L/minute
Standard Deviation 74.21
|
SECONDARY outcome
Timeframe: Average of the last 7 days of treatment (week 4)Measurements conducted by patient in morning upon rising, before intake of morning dose of investigational product but after clearing out mucus. Patients was to refrain from taking rescue medication prior to measurement if possible.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Morning PEF During Last 7 Days of Treatment
|
190.2 L/minute
Standard Deviation 77.24
|
196.4 L/minute
Standard Deviation 83.81
|
SECONDARY outcome
Timeframe: Average of 10 days of pre-treatment measurements (day -10 to -1)Measurement conducted by patient in evening.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Evening PEF at Baseline
|
192.3 L/minute
Standard Deviation 74.27
|
196.2 L/minute
Standard Deviation 79.92
|
SECONDARY outcome
Timeframe: Average of the last 7 days of treatment (week 4)Measurement conducted by patient in evening.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Evening PEF During Last 7 Days of Treatment
|
191.9 L/minute
Standard Deviation 82.17
|
204.7 L/minute
Standard Deviation 87.98
|
SECONDARY outcome
Timeframe: Average of 7 days of pre-treatment measurements (day -7 to -1)The EXACT Tool is a Patient Reported Outcome (PRO) measure; 14 items evaluated on 5- or 6-point scales; total score ranges from 0 to 100 (higher values indicate more severe exacerbation). Baseline is the mean value over the 7 days prior to randomisation.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score at Baseline
|
44.4 Units on scale, 0-100
Standard Deviation 6.99
|
45.7 Units on scale, 0-100
Standard Deviation 8.49
|
SECONDARY outcome
Timeframe: Average of the last 7 days of treatment (week 4)The EXACT Tool is a Patient Reported Outcome (PRO) measure; 14 items evaluated on 5- or 6-point scales; total score ranges from 0 to 100 (higher values indicate more severe exacerbation).
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
EXACT Total Score During Last 7 Days of Treatment
|
43.8 Units on scale, 0-100
Standard Deviation 7.78
|
44.6 Units on scale, 0-100
Standard Deviation 9.84
|
SECONDARY outcome
Timeframe: Average of 10 days of pre-treatment measurements (day -10 to -1)The BCSS scale includes one question for each of the symptoms of breathlessness, cough, and sputum. The total BCSS score ranges from 0 to 12; higher scores indicate greater symptom severity. The minimally important difference has been defined as a change in total score of greater than 0.3 units. Baseline is mean of 10 days prior to treatment.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Breathlessness, Cough and Sputum Scale (BCSS) (Evening) Total Score at Baseline
|
5.2 Units on scale, 0-12
Standard Deviation 1.40
|
5.3 Units on scale, 0-12
Standard Deviation 1.82
|
SECONDARY outcome
Timeframe: Average of the last 7 days of treatment (week 4)The BCSS scale includes one question for each of the symptoms of breathlessness, cough, and sputum. The total BCSS score ranges from 0 to 12; higher scores indicate greater symptom severity. The minimally important difference has been defined as a change in total score of greater than 0.3 units.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
BCSS (Evening) Total Score During Last 7 Days of Treatment
|
5.1 Units on scale, 0-12
Standard Deviation 1.68
|
5.1 Units on scale, 0-12
Standard Deviation 2.25
|
SECONDARY outcome
Timeframe: Average of the last 7 days of treatment (week 4)Number of inhalations of short acting β2 agonist (SABA) or short acting muscarinic antagonist (SAMA) per day.
Outcome measures
| Measure |
AZD2423 100 mg
n=30 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=29 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Rescue Medication Use During the Last 7 Days of Treatment
|
4.0 Inhalations
Full Range 1.0 • Interval 1.0 to 19.3
|
3.5 Inhalations
Full Range 1.0 • Interval 1.0 to 7.9
|
SECONDARY outcome
Timeframe: Day 1The SGRQ-C includes 40 questions in 3 domains: Symptoms (distress due to respiratory symptoms, 7 questions), Activity (disturbance of physical activity, 13 questions), Impacts (overall impact on daily life and well-being, 20 questions). Scores are expressed as a percentage. Baseline is Day 1.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
St George's Respiratory Questionnaire for COPD (SGRQ) Total Score at Baseline
|
55.9 Percent of maximum possible score
Standard Deviation 14.96
|
57.0 Percent of maximum possible score
Standard Deviation 19.27
|
SECONDARY outcome
Timeframe: week 4Decrease in score represents improved Quality of Life; increase represents deteriorated Quality of Life. An increase or decrease of 4 or more percent units is judged as the Minimal Clinically Important Difference.
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
SGRQ Total Score at End of Treatment
|
52.0 Percent of maximum possible score
Standard Deviation 14.38
|
52.9 Percent of maximum possible score
Standard Deviation 18.04
|
SECONDARY outcome
Timeframe: Day 1Baseline = Day 1 = Visit 2
Outcome measures
| Measure |
AZD2423 100 mg
n=29 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
CCL2 (Chemokine Ligand for CCR2b Receptor) Concentration in Plasma at Baseline
|
294 pg/mL
Interval 83.0 to 530.0
|
279 pg/mL
Interval 111.0 to 635.0
|
SECONDARY outcome
Timeframe: week 4End of treatment = 4 weeks = Visit 6
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
CCL2 Concentration in Plasma at End of Treatment
|
1286 pg/mL
Interval 297.0 to 2410.0
|
272 pg/mL
Interval 97.0 to 543.0
|
SECONDARY outcome
Timeframe: Day 1Baseline = Day 1 = Visit 2
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Serum Amyloid-A (SAA) Concentration in Plasma at Baseline
|
5175 ng/mL
Interval 964.0 to 54100.0
|
4044 ng/mL
Interval 376.0 to 18600.0
|
SECONDARY outcome
Timeframe: week 4End of treatment = 4 weeks = Visit 6
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 Participants
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
SAA Concentration in Plasma at End of Treatment
|
6325 ng/mL
Interval 671.0 to 115000.0
|
4032 ng/mL
Interval 211.0 to 320000.0
|
SECONDARY outcome
Timeframe: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4PK-model: 1-compartment population model with first order absorption. AUC was estimated at steady state
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Areaa Under the Curve From 0 to 24 Hours (AUC 0-24), Population Pharmacokinetic Evaluation of AZD2423 at Steady State
|
2780 nmol*h/L
Interval 1370.0 to 5410.0
|
—
|
SECONDARY outcome
Timeframe: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4PK-model: 1-compartment population model with first order absorption. Cmaxwas estimated at steady state
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Cmax, Population Pharmacokinetic Evaluation of AZD2423 at Steady State
|
198 nmol/L
Interval 90.7 to 442.0
|
—
|
SECONDARY outcome
Timeframe: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4PK-model: 1-compartment population model with first order absorption. tmax was estimated at steady state
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Time to Reach Maximum Concentration (Tmax) Population Pharmacokinetic Evaluation of AZD2423 at Steady State
|
1.01 Hours
Interval 0.82 to 1.06
|
—
|
SECONDARY outcome
Timeframe: 2 blood samples (pre- and post dose) per visit collected at weeks 1, 2 and 4PK-model: 1-compartment population model with first order absorption. (Vss/F) was estimated at steady state
Outcome measures
| Measure |
AZD2423 100 mg
n=31 Participants
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Apparent Volume of Distribution at Steady State (Vss/F) Population Pharmacokinetic Evaluation of AZD2423 at Steady State
|
1600 L
Interval 602.0 to 3650.0
|
—
|
Adverse Events
AZD2423 100 mg
Placebo
Serious adverse events
| Measure |
AZD2423 100 mg
n=31 participants at risk
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 participants at risk
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
3.2%
1/31 • Number of events 1
|
0.00%
0/32
|
|
Cardiac disorders
Atrial Flutter
|
3.2%
1/31 • Number of events 1
|
0.00%
0/32
|
Other adverse events
| Measure |
AZD2423 100 mg
n=31 participants at risk
Two 50 mg AZD2423 tablets, once daily for 28 days
|
Placebo
n=32 participants at risk
Placebo to match AZD2423 50 mg tablets, once daily for 28 days
|
|---|---|---|
|
Gastrointestinal disorders
Dry Mouth
|
6.5%
2/31
|
3.1%
1/32
|
|
Infections and infestations
Nasopharyngitis
|
6.5%
2/31
|
0.00%
0/32
|
|
Nervous system disorders
Headache
|
6.5%
2/31
|
3.1%
1/32
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Institutions or Investigators were permitted to publish or present the study results from their site (or the overall results), providing the article or presentation was submitted to and approved by AstraZeneca beforehand.
- Publication restrictions are in place
Restriction type: OTHER