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NCT02796651

Formoterol Dose Ranging Study (ACHIEVE Duaklir USA Phase IIb)

Completed Phase 2 Results posted Last updated 7 February 2018
What this trial tests

Phase 2 trial testing Formoterol fumarate (6 μg) in Chronic Obstructive Pulmonary Disease - COPD in 132 participants. Completed in 7 December 2016.

Timeline
30 June 2016
Primary endpoint
7 December 2016
7 December 2016

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingdouble
Primary purposetreatment
Enrollment132
Start date30 June 2016
Primary completion7 December 2016
Estimated completion7 December 2016
Sites20 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 40 to 130, any sex, with Chronic Obstructive Pulmonary Disease - COPD. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Normalized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Over the 12 h Period Immediately After Morning Study Drug Administration, AUC0-12/12h at Day 7 on Treatment Primary · Day 7: 30 min, 1 to 4 hours, 6 hours, 9 hours and 12 hours post-dose

To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) twice daily (BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate(20 μg). Pre-dose spirometry was performed before the morning daily dose at Day 1 and Day 7 of each treatment period. Two sets of measurements were performed during the hour preceding the scheduled morning study drug administration, allowing approximately 30 minutes between them. Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation.

GroupValue95% CI
Formoterol Fumarate 6 μg0.1080.073 – 0.143
Formoterol Fumarate (FF) 12 μg0.1170.082 – 0.151
Formoterol Fumarate (FF) 24 μg0.1610.125 – 0.197
Perforomist 20 μg0.1220.087 – 0.156
Placebo (Lactose Monohydrate)0.000-0.055 – 0.054
Change From Baseline in FEV1 AUC0-6/6h at Day 1 on Treatment Secondary · Day 1: zero time to 6 hours post-dose

To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg and 40 μg). 6-hour serial spirometry was performed at Day 1 of each treatment period: spirometry was performed post-dose at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours and 6 hours post-dose.

GroupValue95% CI
Formoterol Fumarate 6 μg0.1110.077 – 0.145
Formoterol Fumarate (FF) 12 μg0.1480.115 – 0.182
Formoterol Fumarate (FF) 24 μg0.2050.171 – 0.239
Perforomist 20 μg0.1950.162 – 0.229
Perforomist 40 μg0.2460.212 – 0.280
Placebo (Lactose Monohydrate)-0.019-0.063 – 0.025
Change From Baseline in FEV1 AUC0-6/6h at Day 7 on Treatment Secondary · Day 7: zero time to 6 hours post-dose

To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg). 6-hour serial spirometry was performed at Day 7 of each treatment period: spirometry was performed post-dose at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours and 6 hours post-dose Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation

GroupValue95% CI
Formoterol Fumarate 6 μg0.1660.127 – 0.205
Formoterol Fumarate (FF) 12 μg0.1770.139 – 0.215
Formoterol Fumarate (FF) 24 μg0.2250.186 – 0.265
Perforomist 20 μg0.1860.147 – 0.225
Placebo (Lactose Monohydrate)0.007-0.050 – 0.064
Change From Baseline in Morning Pre-dose (Trough) FEV1 at Day 7 on Treatment Secondary · At baseline and Day 7

To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg). Trough value was defined as the mean of the 2 pre-dose measurements on Day 7. If 1 of the 2 measurements was missing, the non-missing measurement was used as the trough value. Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation.

GroupValue95% CI
Formoterol Fumarate 6 μg0.0770.044 – 0.109
Formoterol Fumarate (FF) 12 μg0.0670.035 – 0.098
Formoterol Fumarate (FF) 24 μg0.1020.069 – 0.135
Perforomist 20 μg0.0610.029 – 0.092
Placebo (Lactose Monohydrate)0.002-0.059 – 0.063

Adverse events — posted to ClinicalTrials.gov

Time frame: From the time of signature of informed consent throughout the treatment period and including the follow-up period (i.e. 2 weeks after the last IP).. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Formoterol Fumarate 6 μg
Serious: 1/107 (1%)
Deaths: 0/107
Formoterol Fumarate (FF) 12 μg
Serious: 2/121 (2%)
Deaths: 1/121
Formoterol Fumarate (FF) 24 μg
Serious: 0/105 (0%)
Deaths: 0/105
Perforomist 20 μg
Serious: 0/118 (0%)
Deaths: 0/118
Perforomist 40 μg
Serious: 1/109 (1%)
Deaths: 0/109
Placebo (Lactose Monohydrate)
Serious: 1/38 (3%)
Deaths: 0/38

Serious adverse events (5 terms)

ReactionSystemFormoterol Fumarate 6 μgFormoterol Fumarate (FF) 1…Formoterol Fumarate (FF) 2…Perforomist 20 μgPerforomist 40 μgPlacebo (Lactose Monohydra…
Squamous cell carcinoma of lungNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Myocardial infarctionCardiac disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Vascular stent occlusionGeneral disorders
Multiple injuriesInjury, poisoning and procedural complications
Other adverse events (5 terms — click to expand)

ReactionSystemFormoterol Fumarate 6 μgFormoterol Fumarate (FF) 1…Formoterol Fumarate (FF) 2…Perforomist 20 μgPerforomist 40 μgPlacebo (Lactose Monohydra…
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Muscle spasmsMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Squamous cell carcinoma of lung, Myocardial infarction, Chronic obstructive pulmonary disease, Vascular stent occlusion, Multiple injuries.

Data from ClinicalTrials.gov NCT02796651 adverse events section.

Sponsor's own description

To assess the bronchodilation of three doses of formoterol fumarate (6 μg, 12 μg and 24 μg) twice daily (BID) administered via Pressair® compared to placebo and to open-label nebulized formoterol fumarate (20 μg and 40 μg).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. A knowledge graph of clinical trials ([Formula: see text]).
    Chen Z, Peng B, Ioannidis VN, Li M, et al · · 2022 · cited 11× · PMID 35304504 · DOI 10.1038/s41598-022-08454-z

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