Phase 2
Completed N=73
A Single Inhalation Dose Study to Assess Efficacy, Pharmacokinetics (PK), Safety and Tolerability of AZD8871 in Patients With Long-term Lung Diseases.
Source: ClinicalTrials.gov NCT03645434 ↗Enrolled (actual)
73
Serious AEs
1.9%
Results posted
Dec 2020
Primary outcomePrimary: Change From Baseline in Trough FEV1 at Day 15 — 0.1904; 0.2260; -0.0222 Liters — p=<0.0001
Summary
This study will evaluate the efficacy and safety data of AZD8871 in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This study will determine the 24-hour efficacy (lung function) profile of AZD8871 600 μg relative to placebo dry powder inhaler (DPI) based on trough forced expiratory volume in 1 second (FEV1) following repeated dosing (2 weeks). Anoro® Ellipta® (umeclidinium/vilanterol) once daily is included as an active control. This study aims at providing a novel approach to the treatment of COPD with greater efficacy than single-mechanism bronchodilators, equivalent to long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) administered as free- or fixed-dose combination therapies, with an equivalent or superior safety and tolerability profile.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Trough FEV1 at Day 15 |
0.1904; 0.2260; -0.0222 | <0.0001 sig |
| PRIMARY Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) at Day 1 to Day 8, Day 9 to Day 14, Day 1 to Day 14 |
-2.11; -2.78; -0.57; -2.87; -3.29; -0.52 | 0.0022 sig |
| SECONDARY FEV1 AUC(0-4)/4h (Area Under the Curve for the Change in FEV1 From Baseline to 4h, Normalised by the Time Window) |
0.3604; 0.2912; 0.0430; 0.4296; 0.3796; 0.0808 | — |
| SECONDARY FEV1 AUC(0-8)/8h (Area Under the Curve for the Change in FEV1 From Baseline to 8h, Normalised by the Time Window) |
0.3072; 0.2798; 0.0230; 0.3394; 0.3102; 0.0021 | — |
| SECONDARY FEV1 AUC(0-12)/12h (Area Under the Curve for the Change in FEV1 From Baseline to 12h, Normalised by the Time Window) |
0.2668; 0.2720; 0.0096; 0.3024; 0.2919; -0.0032 | — |
| SECONDARY FEV1 AUC(0-24)/24h (Area Under the Curve for the Change in FEV1 From Baseline to 24h, Normalised by the Time Window) |
0.1832; 0.2333; -0.0132; 0.2223; 0.2417; -0.0324 | — |
| SECONDARY Change From Baseline in Trough FEV1 on Day 2 and Day 8. |
0.1359; 0.2249; 0.0339; 0.2161; 0.2748; 0.0121 | <0.0001 sig |
| SECONDARY Change From Baseline in Peak FEV1 on Day 1, Day 8 and Day 14. |
0.403; 0.333; 0.092; 0.511; 0.454; 0.120 | <0.0001 sig |
| SECONDARY Change From Baseline in Breathlessness, Cough and Sputum Scale (BCSS) Total Score at Day 1 to Day 8, Day 9 to Day 14, Day 1 to Day 14 |
-0.37; -0.61; 0.16; -0.35; -0.63; 0.53 | 0.0010 sig |
| SECONDARY Number of Participants With Adverse Events. |
39; 38; 35; 0; 0; 0 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) |
310.4; 532.9; 26.64; 63.29 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) |
0.99; 0.98; 2.00; 2.00 | — |
| SECONDARY Time to Reach Last Quantifiable Plasma Concentration (Tlast) |
23.93; 24.03; 23.92; 24.03 | — |
| SECONDARY Area Under the Plasma Concentration-curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) |
1655; 4001; 251.9; 943.3 | — |
| SECONDARY Area Under the Plasma Concentration-curve From Time 0 to 24 Hours Post-dose [AUC(0-24)] |
1661; 3996; 289.5; 941.7 | — |
| SECONDARY Average Plasma Concentration During a Dosing Interval (Cavg) |
166.5; 39.23 | — |
| SECONDARY Fluctuation Index During a Dosing Interval (%Fluctuation) |
273.1; 91.03 | — |
| SECONDARY Accumulation Ratio for Cmax (Rac(Cmax)) |
1.725; 2.377 | — |
| SECONDARY Accumulation Ratio for AUC(0-24) Rac(AUC(0-24)) |
2.406; 3.443 | — |
| SECONDARY Change From Baseline in Use of Rescue Medication |
-1.00; -0.95; 0.18; -0.78; -0.87; 0.52 | <0.0001 sig |
Eligibility Criteria
Inclusion Criteria
- Provision of signed and dated, written ICF prior to any study-specific procedures, sampling, and analyses.
- Patient must be 40 to 85 years male and/or females of non-childbearing potential who are not pregnant/lactating at the time of signing the ICF (Screening; Visit 1).
- Patient with an established clinical history of moderate to severe COPD for more than 1 year at Screening, according to the GOLD COPD guidelines.
- Patient who is a current or former smoker (defined as one who has stopped smoking for at least 6 months prior to Screening) with a history of ≥10 pack-years of cigarette smoking [Number of pack-years=(number of cigarettes per day/20)* number of years smoked (eg, 1 pack-year=20 cigarettes smoked per day for 1 year)].
- Patient with post-bronchodilator FEV1/forced vital capacity (FVC) ratio 450 ms for male and >470 ms for female or an ECG that is not suitable for QT measurements (eg, poorly defined termination of the T wave).
- Patient with a heart rate 120 beats per minute (bpm).
- Patient has clinically significant uncontrolled hypertension (>180 mmHg) as assessed by the Investigator.
- Patient has seizures or a history of seizures requiring anticonvulsants within 12 months prior to Screening.
- Patient is taking selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors whose dose has not been stable for at least 4 weeks prior to Screening, or exceeds the maximum recommended dose.
- Patient has a symptomatic bladder neck obstruction, acute urinary retention or symptomatic non-stable prostate hypertrophy.
- Any laboratory abnormality or suspicion of any clinically relevant disease or disorder (on history or examination), including uncontrolled diabetes or hypokalaemia (serum potassium 500 mL of blood and/or plasma within the previous 3 months prior to Screening.
- Vulnerable patients (who has been placed in an institution due to a regulatory or court order).
Data sourced from ClinicalTrials.gov (NCT03645434). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.