Trial Outcomes & Findings for A Double-blind, Placebo-controlled, Crossover Study to Assess the Effect of Aclidinium Bromide 400 μg Bid on COPD Symptoms and Sleep Quality After 3 Weeks of Treatment in Patients With Stable Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02153489)

NCT ID: NCT02153489

Last Updated: 2016-11-09

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 30 participants
• Primary outcome timeframe: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 11, 12, 12.5, 13, 14, 15, 16, 19, 22, 23, and 24 hours at Week 3 of treatment
• Results posted on: 2016-11-09

Participant Flow

This study was conducted by 3 investigators at 3 sites in Germany. The first patient was screened in April 2014 and the last patient visit was in June 2015

All patients who met the study entry criteria and completed the screening assessments and the 7-day run-in period were randomized. Nine (9/39) subjects were not randomized due to screening failure (primarily for non-fulfillment of inclusion/exclusion criteria)

Participant milestones

Measure	Sequence A Aclidinium 400 μg - Placebo	Sequence B Placebo - Aclidinium 400 μg
Period 1 STARTED	15	15
Period 1 COMPLETED	15	15
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	15	15
Period 2 COMPLETED	15	15
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Double-blind, Placebo-controlled, Crossover Study to Assess the Effect of Aclidinium Bromide 400 μg Bid on COPD Symptoms and Sleep Quality After 3 Weeks of Treatment in Patients With Stable Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Measure	Overall Study n=30 Participants All patients participating in the crossover study
Age, Continuous	64.4 Years STANDARD_DEVIATION 7.0 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 11, 12, 12.5, 13, 14, 15, 16, 19, 22, 23, and 24 hours at Week 3 of treatment

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) AUC0-24hr	0.0953 L/sec*hr Standard Error 0.0381	-0.0429 L/sec*hr Standard Error 0.0381

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Morning Trough FEV1	0.1128 Liters/sec Standard Error 0.0395	-0.0106 Liters/sec Standard Error 0.0395

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Peak FEV1	0.1605 Liters/sec Standard Error 0.0391	-0.0149 Liters/sec Standard Error 0.0391

OTHER_PRE_SPECIFIED outcome

Timeframe: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 11 and 12 hours at Week 3 of treatment

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Normalized FEV1 AUC0-12hr	0.1394 L/sec*hr Standard Error 0.0406	-0.0100 L/sec*hr Standard Error 0.0406

OTHER_PRE_SPECIFIED outcome

Timeframe: 12, 12.5, 13, 14, 15, 16, 19, 22, 23, and 24 hours at Week 3 of treatment

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Normalized FEV1 AUC12-24hr	0.0513 L/sec*hr Standard Error 0.0369	-0.0758 L/sec*hr Standard Error 0.0369

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Night-time and early-morning symptoms were recorded every morning using the Early-Morning Symptoms of COPD Instrument [EMSCI] and the Night-time Symptoms of COPD Instrument [NiSCI]. Scores ranged from 0 (no symptoms) to 4 (very severe symptoms). The questionnaires also evaluated nocturnal awakenings and limitation of early-morning activities (scores ranged from 0 [no limitation] to 4 [a very great deal]). Symptoms assessed over 24 weeks included change from baseline in the severity of night-time and early-morning cough, wheezing, shortness of breath and difficulty bringing up phlegm, overall night-time and early-morning symptom severity, number of nocturnal awakenings and limitation of early-morning activities due to COPD symptoms

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in the Average Rating of Overall Early Morning COPD Symptom Severity	-0.07 Score on a scale Standard Deviation 0.575	0.09 Score on a scale Standard Deviation 0.476

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

The evening symptoms questionnaire was filled out after the second medication administration of the day and before bedtime. Scores ranged from 0 (no symptoms) to 4 (very severe symptoms). Symptoms assessed over 24 weeks included change from baseline in the severity of evening cough, wheezing, shortness of breath and tightness of the chest, chest congestion, difficulty bringing up phlegm, overall evening symptom severity, and limitation of evening activities due to COPD symptoms

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in the Average Rating of Overall Evening COPD Symptom Severity	-0.15 Score on a scale Standard Deviation 0.661	0.11 Score on a scale Standard Deviation 0.559

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Night-time and early-morning symptoms were recorded every morning using the Early-Morning Symptoms of COPD Instrument [EMSCI] and the Night-time Symptoms of COPD Instrument [NiSCI]. Scores ranged from 0 (no symptoms) to 4 (very severe symptoms). The questionnaires also evaluated nocturnal awakenings and limitation of early-morning activities (scores ranged from 0 [no limitation] to 4 [a very great deal]). Symptoms assessed over 24 weeks included change from baseline in the severity of night-time and early-morning cough, wheezing, shortness of breath and difficulty bringing up phlegm, overall night-time and early-morning symptom severity, number of nocturnal awakenings and limitation of early-morning activities due to COPD symptoms

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in the Average Rating of Overall Night-time COPD Symptom Severity	-0.14 Score on a scale Standard Deviation 0.612	-0.03 Score on a scale Standard Deviation 0.526

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Night-time and early-morning symptoms were recorded every morning using the Early-Morning Symptoms of COPD Instrument [EMSCI] and the Night-time Symptoms of COPD Instrument [NiSCI]. Scores ranged from 0 (no symptoms) to 4 (very severe symptoms). The questionnaires also evaluated nocturnal awakenings and limitation of early-morning activities (scores ranged from 0 [no limitation] to 4 [a very great deal]). Symptoms assessed over 24 weeks included change from baseline in the severity of night-time and early-morning cough, wheezing, shortness of breath and difficulty bringing up phlegm, overall night-time and early-morning symptom severity, number of nocturnal awakenings and limitation of early-morning activities due to COPD symptoms

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in the Average Rating of COPD Symptoms Limiting Early Morning Activities	-0.02 Score on a scale Standard Deviation 0.457	0.16 Score on a scale Standard Deviation 0.430

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

The evening symptoms questionnaire was filled out after the second medication administration of the day and before bedtime. Scores ranged from 0 (no symptoms) to 4 (very severe symptoms). Symptoms assessed over 24 weeks included change from baseline in the severity of evening cough, wheezing, shortness of breath and tightness of the chest, chest congestion, difficulty bringing up phlegm, overall evening symptom severity, and limitation of evening activities due to COPD symptoms

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in the Average Rating of COPD Symptoms Limiting Evening Activities	-0.18 Score on a scale Standard Deviation 0.488	0.03 Score on a scale Standard Deviation 0.450

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

The Apnea Hypopnea Index (AHI) is used to indicate the severity of obstructive sleep apnea. The AHI is the number of apneas or hypopneas recorded during the study per hour of sleep

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Apnea-hypopnea Index (AHI) Per Hour of Total Sleep Time	0.4767 Events/hr Standard Error 0.4478	0.7700 Events/hr Standard Error 0.4478

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

The oxygen desaturation index (ODI) is the number of times per hour of sleep that the blood's oxygen level drop by a certain degree from baseline. In this study, any event with a 4% decrease in blood oxygen levels counted towards the total

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Oxygen Desaturation Index (ODI) Per Hour of Total Sleep Time	-0.3033 Events/hr Standard Error 0.9754	2.2400 Events/hr Standard Error 0.9754

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Proportion of Sleep Stage REM as a Percentage of Total Sleep Time	1.4100 Percentage of total sleep time Standard Error 0.9851	-1.1167 Percentage of total sleep time Standard Error 0.9851

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Sleep efficiency is calculated as the total sleep time as a proportion of total time in bed

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Sleep Efficiency	1.0000 Percentage of total time in bed Standard Error 2.4046	-2.5500 Percentage of total time in bed Standard Error 2.4046

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Total Sleep Time	6.9200 Minutes Standard Error 11.5802	-11.8500 Minutes Standard Error 11.5802

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Moderate activity was defined as any physical activity >3 metabolic equivalents

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Duration of at Least Moderate Activity	9.4460 Minutes Standard Error 6.7081	-8.5943 Minutes Standard Error 6.5879

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 of treatment

Outcome measures

Measure	Aclidinium n=30 Participants Aclidinium 400 μg BID	Placebo n=30 Participants Placebo BID
Change From Baseline in Number of Steps Per Day	268.5891 Number of steps per day Standard Error 326.3649	22.2652 Number of steps per day Standard Error 320.6754

Adverse Events

Aclidinium

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Aclidinium n=30 participants at risk Aclidinium 400 μg BID	Placebo n=30 participants at risk Placebo BID
Skin and subcutaneous tissue disorders Erythema	10.0% 3/30 • Up to 30 days after last study drug administration	0.00% 0/30 • Up to 30 days after last study drug administration

Additional Information

Study Director

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee Publication of the results by the Investigator will be subject to mutual agreement between the investigator and sponsor.
• Publication restrictions are in place

Restriction type: OTHER