Trial Outcomes & Findings for AMPLIFY - D6571C00001 Duaklir USA Phase III Study (NCT NCT02796677)

Last Updated: 2018-11-09

Results Overview

To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 at 1 hour post-dose of AB/FF 400/12 µg compared to AB 400 μg after administration of oral inhalation powder BID via DIP to participants with COPD. Baseline was defined as the average of the two FEV1 values measured just prior to the administration of the first dose of investigational product (IP) at randomization Visit. If one of the two was missing, then the available one would be used as baseline value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1595 participants

Primary outcome timeframe

At baseline 1-hour postdose and Week 24

Results posted on

2018-11-09

Participant Flow

Study was conducted on participants with stable chronic obstructive pulmonary disease (COPD), in 11 countries: United States (US), Germany, Poland, Hungary, Bulgaria, Ukraine, United Kingdom (UK), Czech Republic, Spain, Israel \& Russia (was not finally started). First participant enrolled was 05 July 2016 \& participant last visit was 08 June 2017

Eligible Participants signed informed consent form (ICF) \& entered screening (Run-in) period (14 ± 3 days), inclusion/exclusion criteria were checked by medical \& COPD history, physical examination, laboratory analysis, electrocardiogram, \& COPD severity (COPD Assessment Test \[CAT\] \& post-bronchodilator forced expiratory volume in 1 second \[FEV1\])

Participant milestones

Participant milestones
Measure	Aclidinium Bromide (AB)/Formoterol Fumarate (FF) 400/12 μg Randomized participants received AB 400 μg/FF 12 μg oral inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg Randomized participants received FF 12 μg oral inhalation powder BID via DPI.	Tiotropium (TIO) 18 μg Randomized participants received TIO 18 μg oral inhalation powder in capsule BID via DPI.
Overall Study STARTED	317	478	320	479
Overall Study Completed Treatment and Follow-up	279	405	267	403
Overall Study COMPLETED	279	405	267	405
Overall Study NOT COMPLETED	38	73	53	74

Reasons for withdrawal

Reasons for withdrawal
Measure	Aclidinium Bromide (AB)/Formoterol Fumarate (FF) 400/12 μg Randomized participants received AB 400 μg/FF 12 μg oral inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg Randomized participants received FF 12 μg oral inhalation powder BID via DPI.	Tiotropium (TIO) 18 μg Randomized participants received TIO 18 μg oral inhalation powder in capsule BID via DPI.
Overall Study Adverse Event	11	22	14	14
Overall Study Protocol Violation	7	5	4	8
Overall Study Lost to Follow-up	1	5	2	2
Overall Study Lack of Efficacy	7	9	14	20
Overall Study Withdrawal by Subject	4	14	6	7
Overall Study Progressive disease	6	15	13	18
Overall Study Reason not mentioned	2	3	0	5

Baseline Characteristics

Safety analysis set: All randomized participants who took at least one dose of investigational medicinal product (IMP).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aclidinium Bromide (AB)/Formoterol Fumarate (FF) 400/12 μg n=314 Participants Randomized participants received AB 400 μg/FF 12 μg oral inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg n=475 Participants Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg n=319 Participants Randomized participants received FF 12 μg oral inhalation powder BID via DPI.	Tiotropium (TIO) 18 μg n=475 Participants Randomized participants received TIO 18 μg oral inhalation powder in capsule BID via DPI.	Total n=1583 Participants Total of all reporting groups
Age, Continuous	64.4 Years STANDARD_DEVIATION 8.5 • n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of investigational medicinal product (IMP).	64.4 Years STANDARD_DEVIATION 8.1 • n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of investigational medicinal product (IMP).	64.7 Years STANDARD_DEVIATION 8.3 • n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of investigational medicinal product (IMP).	64.0 Years STANDARD_DEVIATION 8.6 • n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of investigational medicinal product (IMP).	64.3 Years STANDARD_DEVIATION 8.4 • n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of investigational medicinal product (IMP).
Sex: Female, Male Female	121 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	171 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	129 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	199 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	620 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.
Sex: Female, Male Male	193 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	304 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	190 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	276 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	963 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	1 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	1 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.
Race (NIH/OMB) Asian	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	2 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	2 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	4 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	28 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	16 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	16 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	77 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.
Race (NIH/OMB) White	297 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	444 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	303 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	457 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	1501 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=7 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=5 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=4 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.	0 Participants n=21 Participants • Safety analysis set: All randomized participants who took at least one dose of IMP.

PRIMARY outcome

Timeframe: At baseline 1-hour postdose and Week 24

Population: Intention-to Treat (ITT) population: All randomized participants who took at least one dose of IP and had at least a baseline FEV1, under the ITT principle and regardless the adherence to the randomized treatment.

Outcome measures

Outcome measures
Measure	AB/FF 400/12 μg n=314 Participants Randomized participants received orally AB 400 μg/FF 12 μg inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg n=475 Participants Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg n=319 Participants Randomized participants received orally FF 12 μg inhalation powder BID via DPI.	TIO 18 μg n=475 Participants Edit Randomized participants received orally TIO 18 μg inhalation powder in capsule BID via DPI.
Change From Baseline in 1-hour Morning Post-dose Dose Forced Expiratory Volume in 1 Second (FEV1) of AB/FF 400/12 μg Compared to AB 400 μg at Week 24	0.253 Litres Standard Error 0.013	0.169 Litres Standard Error 0.011	0.168 Litres Standard Error 0.013	0.161 Litres Standard Error 0.011

PRIMARY outcome

Timeframe: At baseline morning predose and Week 24

Population: ITT population: All randomized participants who took at least one dose of IP and had at least a baseline FEV1, under the ITT principle and regardless the adherence to the randomized treatment.

To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough) of AB/FF 400/12 µg compared to FF 12 μg after administration of oral inhalation powder BID via DPI to participants with COPD. Morning pre-dose (trough) FEV1 was defined as the average of the corresponding -30 minute and 0 minute before the morning study medication at Week 24. If one time-point was missing then the available one would be used as morning pre-dose.

Outcome measures

Outcome measures
Measure	AB/FF 400/12 μg n=314 Participants Randomized participants received orally AB 400 μg/FF 12 μg inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg n=475 Participants Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg n=319 Participants Randomized participants received orally FF 12 μg inhalation powder BID via DPI.	TIO 18 μg n=475 Participants Edit Randomized participants received orally TIO 18 μg inhalation powder in capsule BID via DPI.
Change From Baseline in Morning Predose (Trough) FEV1 of AB/FF 400/12 μg Compared to FF 12 μg at Week 24	0.080 Litres Standard Error 0.014	0.066 Litres Standard Error 0.012	0.025 Litres Standard Error 0.014	0.060 Litres Standard Error 0.012

PRIMARY outcome

Timeframe: At baseline morning predose and Week 24

Population: Per-Protocol (PP) population: A subset of the ITT population, consisted of participants who met all inclusion/exclusion criteria liable to affect the efficacy assessment, had sufficient treatment compliance, and did not present serious deviations of the protocol that might affect efficacy.

To assess the non-inferior bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough)of AB 400 µg compared to TIO 18 μg after administration of oral inhalation powder BID via DPI to participants with COPD.

Outcome measures

Outcome measures
Measure	AB/FF 400/12 μg n=423 Participants Randomized participants received orally AB 400 μg/FF 12 μg inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg n=419 Participants Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg Randomized participants received orally FF 12 μg inhalation powder BID via DPI.	TIO 18 μg Edit Randomized participants received orally TIO 18 μg inhalation powder in capsule BID via DPI.
Change From Baseline in Morning Predose (Trough) FEV1 at Week 24 Comparing AB 400 μg Versus TIO 18 μg to Demonstrate Non-inferiority	0.064 Litres Standard Error 0.013	0.057 Litres Standard Error 0.013	—	—

SECONDARY outcome

Timeframe: At Day 1 and Day 169

To assess the bronchodilatory effect by evaluating the mean changes from baseline in nAUC0-3/3h FEV1 of AB/FF 400/12 µg compared to AB 400 μg and and FF 12 μg after administration of oral inhalation powder BID via DPI to participants with COPD.

Outcome measures

Outcome measures
Measure	AB/FF 400/12 μg n=314 Participants Randomized participants received orally AB 400 μg/FF 12 μg inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg n=475 Participants Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg n=319 Participants Randomized participants received orally FF 12 μg inhalation powder BID via DPI.	TIO 18 μg n=475 Participants Edit Randomized participants received orally TIO 18 μg inhalation powder in capsule BID via DPI.
Change From Baseline in Normalized Area Under Curve 3hours Post-dose (nAUC0-3/3h) FEV1 of AB/FF 400/12 μg Compared to AB 400 μg and and FF 12 μg at Week 24	0.237 Litres Standard Error 0.013	0.162 Litres Standard Error 0.010	0.149 Litres Standard Error 0.013	0.151 Litres Standard Error 0.010

SECONDARY outcome

Timeframe: At baseline and Week 24

SGRQ was a A standardized self-completed tool used to measure impaired health and perceived well-being ("quality of life") in respiratory diseases. The questionnaire contained 50 items divided into 3 (symptoms, activity and impacts) dimensions. Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100%, zero score indicating no impairment of life quality. A summary score utilizing responses to all items is the total SGRQ score which also ranges from 0 to 100%. The SGRQ scores are calculated using weights attached to each item of the questionnaire which provides an estimate of the distress associated with the symptoms or state described in each item. Higher scores indicate poorer health. A decrease of at least 4 units in the SGRQ total score has been established as the criterion for minimal meaningful improvement. SGRQ responders will be those with a decrease in SGRQ total score of at least 4 units from baseline.

Outcome measures

Outcome measures
Measure	AB/FF 400/12 μg n=270 Participants Randomized participants received orally AB 400 μg/FF 12 μg inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg n=383 Participants Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg n=258 Participants Randomized participants received orally FF 12 μg inhalation powder BID via DPI.	TIO 18 μg n=389 Participants Edit Randomized participants received orally TIO 18 μg inhalation powder in capsule BID via DPI.
Responder (Number of Participants) Analysis of St. George's Respiratory Questionnaire (SGRQ) Total Score With AB/FF 400/12 μg Versus AB 400 μg and FF 12 μg. Number of responders -Yes	130 Participants	188 Participants	128 Participants	197 Participants
Responder (Number of Participants) Analysis of St. George's Respiratory Questionnaire (SGRQ) Total Score With AB/FF 400/12 μg Versus AB 400 μg and FF 12 μg. Number of responders- NO	140 Participants	195 Participants	130 Participants	192 Participants

Adverse Events

AB/FF 400/12 μg

Serious events: 23 serious events

Other events: 173 other events

Deaths: 1 deaths

AB 400 μg

Serious events: 41 serious events

Other events: 222 other events

Deaths: 1 deaths

FF 12 μg

Serious events: 22 serious events

Other events: 178 other events

Deaths: 4 deaths

TIO 18 μg

Serious events: 37 serious events

Other events: 241 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	AB/FF 400/12 μg n=314 participants at risk Randomized participants received orally AB 400 μg/FF 12 μg inhalation powder twice daily (BID) via dry powder inhaler (DPI).	AB 400 μg n=475 participants at risk Randomized participants received AB 400 μg oral inhalation powder BID via DPI.	FF 12 μg n=319 participants at risk Randomized participants received orally FF 12 μg inhalation powder BID via DPI.	TIO 18 μg n=475 participants at risk Randomized participants received orally TIO 18 μg inhalation powder in capsule BID via DPI.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary	15.6% 49/314 • Number of events 60 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	16.6% 79/475 • Number of events 90 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	18.2% 58/319 • Number of events 74 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	12.8% 61/475 • Number of events 70 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Infections and infestations Nasopharyngitis	11.5% 36/314 • Number of events 42 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	9.9% 47/475 • Number of events 56 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	12.2% 39/319 • Number of events 45 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	13.5% 64/475 • Number of events 67 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Nervous system disorders Headache	5.1% 16/314 • Number of events 27 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	4.0% 19/475 • Number of events 20 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	5.3% 17/319 • Number of events 19 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	5.3% 25/475 • Number of events 31 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Infections and infestations Upper respiratory tract infection	2.5% 8/314 • Number of events 9 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.7% 13/475 • Number of events 15 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.2% 7/319 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	3.6% 17/475 • Number of events 21 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 6/314 • Number of events 6 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.7% 13/475 • Number of events 18 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.9% 6/319 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.5% 12/475 • Number of events 12 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Musculoskeletal and connective tissue disorders Back pain	4.8% 15/314 • Number of events 22 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.5% 7/475 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.5% 8/319 • Number of events 12 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.5% 7/475 • Number of events 8 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Respiratory, thoracic and mediastinal disorders Cough	1.9% 6/314 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.5% 7/475 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.3% 4/319 • Number of events 4 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	3.6% 17/475 • Number of events 19 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Infections and infestations Sinusitis	2.5% 8/314 • Number of events 8 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.1% 10/475 • Number of events 10 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.9% 6/319 • Number of events 6 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.5% 7/475 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Vascular disorders Hypertension	2.2% 7/314 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.7% 8/475 • Number of events 8 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.8% 9/319 • Number of events 10 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.5% 7/475 • Number of events 9 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Infections and infestations Pneumonia	1.3% 4/314 • Number of events 4 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	0.21% 1/475 • Number of events 1 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.9% 6/319 • Number of events 6 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.3% 6/475 • Number of events 6 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Gastrointestinal disorders Diarrhoea	1.9% 6/314 • Number of events 6 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.9% 9/475 • Number of events 9 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.2% 7/319 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.5% 7/475 • Number of events 7 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Musculoskeletal and connective tissue disorders Arthralgia	2.5% 8/314 • Number of events 9 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	0.84% 4/475 • Number of events 4 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	0.94% 3/319 • Number of events 4 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.7% 8/475 • Number of events 10 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.
Infections and infestations Urinary tract infection	1.3% 4/314 • Number of events 4 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	1.1% 5/475 • Number of events 5 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	2.5% 8/319 • Number of events 8 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.	0.63% 3/475 • Number of events 3 • From time of signature of the ICF throughout the treatment period and including the follow-up period (14 days after the last study drug administration) An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition might be symptoms, signs or the abnormal results of an investigation. The safety population was defined as all randomized patients who took at least one dose of IMP.

Additional Information

Global Clinical Leader

AstraZeneca AB

Phone: +46 766 346712

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All clinical study findings and documents will be regarded as confidential. The investigator and members of his/her research team must not disclose such information without prior written approval from the sponsor.
Publication restrictions are in place

Restriction type: OTHER