Phase 2
Completed N=42
Efficacy, Pharmacokinetics (PK), Safety and Tolerability Study of Inhaled AZD8871
Source: ClinicalTrials.gov NCT02971293 ↗Enrolled (actual)
42
Serious AEs
1.8%
Results posted
Jun 2019
Primary outcomePrimary: Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) — 0.168; 0.267; 0.007 L — p=<0.001
Summary
This is a study to evaluate the effects of AZD8871 in patients with COPD. Adult male or female patients with moderate to severe COPD, who agree to be in this study, will receive 3 treatments, i.e. 2 different doses of AZD8871 and placebo (dummy medication containing no drug) at once a day for 2 weeks, in a random order. To make the comparison between AZD8871 and placebo as fair as possible, this study is "double blinded." This means that neither patient nor the study doctor will know in which order the 3 treatments will be given. This study will include patients who are between 40 and 80 years of age. In total there will be 42 patients participating in this study at two study centers in the United Kingdom and Germany. The study will have a total of 12 visits for each patient spanning for a period of 4 to 6 months. The study is anticipated to run for approximately 8 months and should not exceed 10 months.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) |
0.168; 0.267; 0.007 | <0.001 sig |
| SECONDARY Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose) |
61.05; 290.8; 7.796; 33.87; 187.7; 1016 | — |
| SECONDARY Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14) |
72.52; 381.8; 11.89; 63.17; 221.4; 1152 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose) |
0.93; 1.46; 1.92; 2.02; 3.94; 3.98 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14) |
0.93; 1.00; 1.96; 2.00; 3.92; 4.02 | — |
| SECONDARY AUClast of AZD8871 and Its Metabolites (Single Dose) |
301.0; 1777; 60.06; 358.5; 1414; 9299 | — |
| SECONDARY AUClast of AZD8871 and Its Metabolites (Multiple Doses, Day 14) |
539.2; 3156; 160.2; 935.9; 1964; 13050 | — |
| SECONDARY AUC0-24 of AZD8871 and Its Metabolites (Single Dose) |
326.1; 1776; 135.6; 358.1; 0; 10440 | — |
| SECONDARY AUC0-24 of AZD8871 and Its Metabolites (Multiple Doses, Day 14) |
538.4; 3152; 179.4; 933.8; 3281; 13030 | — |
| SECONDARY Accumulation Ratio for Cmax (RacCmax) of AZD8871 and Its Metabolites (Day 14) |
1.263; 1.385; 1.594; 1.968; 1.257; 1.133 | — |
| SECONDARY Accumulation Ratio for AUC0-24 (RacAUC[0-24]) of AZD8871 and Its Metabolites (Day 14) |
1.893; 1.878; 1.576; 2.721; 1.24; 1.326 | — |
| SECONDARY Cavg of AZD8871 and Its Metabolites During a Dosing Interval (Day 14) |
22.44; 131.4; 7.478; 38.94; 136.7; 543.3 | — |
| SECONDARY Change From Baseline in Trough FEV1 at Day 1 (Single Dose) |
0.092; 0.161; 0.006 | 0.002 sig |
| SECONDARY Change From Baseline in Trough FEV1 at Day 8 (Pre-dose) |
0.180; 0.232; 0.032 | <0.001 sig |
| SECONDARY Change From Baseline in Trough FEV1 Over the Treatment Duration (Days 1-15) |
0.146; 0.215; 0.016 | <0.001 sig |
| SECONDARY Change From Baseline in Peak FEV1 at Day 1 (Single Dose) |
0.376; 0.469; 0.076 | <0.001 sig |
| SECONDARY Change From Baseline in Peak FEV1 at Day 8 |
0.486; 0.556; 0.136 | <0.001 sig |
| SECONDARY Change From Baseline in Peak FEV1 at Day 14 |
0.476; 0.522; 0.095 | <0.001 sig |
| SECONDARY Change From Baseline in Peak FEV1 Over the Treatment Duration (Days 1-15) |
0.438; 0.511; 0.102 | <0.001 sig |
| SECONDARY Change From Baseline in BCSS Questionnaire Total Score From Day 1 to Day 8 Post-treatment |
-0.416; -0.920; -0.071 | 0.205 |
| SECONDARY Change From Baseline in BCSS Questionnaire Total Score From Day 9 to Day 14 Post-treatment |
-0.491; -1.191; -0.030 | 0.111 |
| SECONDARY Change From Baseline in Cough Individual Domain Score From Day 1 to Day 8 Post-treatment |
-0.186; -0.287; -0.134 | 0.621 |
| SECONDARY Change From Baseline in Cough Individual Domain Score From Day 9 to Day 14 Post-treatment |
-0.160; -0.445; -0.123 | 0.748 |
| SECONDARY Change From Baseline in Breathlessness Individual Domain Score From Day 1 to Day 8 Post-treatment |
-0.122; -0.377; 0.099 | 0.064 |
| SECONDARY Change From Baseline in Breathlessness Individual Domain Score From Day 9 to Day 14 Post-treatment |
-0.202; -0.453; 0.106 | 0.018 sig |
| SECONDARY Change From Baseline in Sputum Individual Domain Score From Day 1 to Day 8 Post-treatment |
-0.100; -0.255; -0.035 | 0.477 |
| SECONDARY Change From Baseline in Sputum Individual Domain Score From Day 9 to Day 14 Post-treatment |
-0.122; -0.297; -0.011 | 0.213 |
Eligibility Criteria
Inclusion Criteria
- Patient who provided of informed consent prior to any study-specific procedures
- Male or female 40 to 80 years of age (both inclusive) at Screening (Visit 1). A female is eligible to enter and participate in the study if she is of non-childbearing potential.
Note: A female is considered to be of non-childbearing potential if she meets one of the following criteria:
- Permanently or surgically sterilised, including hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy
- Post-menopausal; aged 750 mL at Visit 2. If criterion is not met, the test can be repeated at the latest, up to Day 14.
- Patient who fulfils reversibility criteria to salbutamol at Visit 2. Reversibility is defined as ≥12% and ≥200 mL increase in FEV1 after inhalation of 4 puffs of salbutamol. (400 µg). If criterion is not met, the test can be repeated at the latest, up to Day 14.
- Patient is willing and, in the opinion of the Investigator, able to change current COPD therapy as required by the protocol and willing to use ipratropium Four times a day (if needed, during run-in and wash-out periods) with or without Inhaled corticosteroid for maintenance therapy of COPD and as needed rescue salbutamol from Visit 1 up Visit 11.
- Patient is free from any clinically active disease other than COPD that may impact study outcome, as determined by medical history, physical examination, laboratory testing, and 12-lead ECG findings, at Screening.
- Patient is willing to remain at the study centre as required per protocol to complete all visit assessments.
- Patient with body mass index (BMI) 500 mL of blood and plasma within the previous 3 months prior to screening.
- Patient is unlikely to co-operate with the requirements of the study, instructions of the Principal Investigator., or have e-dairy completion rate of < 70% during the run in period.
- Patient with known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection.
Data sourced from ClinicalTrials.gov (NCT02971293). 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.