Trial Outcomes & Findings for Roflumilast and Donepezil to Reverse Scopolamine Induced Cognitive Deficits in Healthy Adults (NCT NCT02051335)
NCT ID: NCT02051335
Last Updated: 2017-02-01
Results Overview
VRM measures the ability to encode and subsequently retrieve verbal information. This task begins with the first presentation phase in which 18 words are shown in turn on the screen. The participant is then asked to recall as many words as possible during the first immediate recall phase. The same 18 words are then shown in a second presentation phase which is followed by a second immediate recall phase. After a delay of approximately 20-30 minutes, a delayed recall stage is completed. The possible range of correct responses is 0 (worst) to 18 (best). Higher number of correct responses in the test indicates a better outcome. A negative change from baseline indicates a worsening of the score.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
27 participants
Primary outcome timeframe
Baseline and 1 hour after scopolamine administration on Day 1 of each treatment period. Baseline is defined as the assessment 1 hour before roflumilast/donepezil administration (3 hours before scopolamine administration).
Results posted on
2017-02-01
Participant Flow
Participants took part in the study at 1 investigative site in the United Kingdom from 16 January 2014 to 17 May 2014.
Participants with a diagnosis of Alzeimer's disease were enrolled equally in a 4 period, 4 treatment crossover study. Treatment A: Placebo, Treatment B: Donepezil, Treatment C: Roflumilast and Treatment D: Roflumilast + Donepezil. All participants received scopolamine on Day 1 of each treatment period.
Participant milestones
| Measure |
Sequence 1 (ABDC)
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period.
|
Sequence 2 (BCAD)
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period.
|
Sequence 3 (CDBA)
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period.
|
Sequence 4 (DACB)
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period.
|
|---|---|---|---|---|
|
Period 1
STARTED
|
7
|
7
|
7
|
6
|
|
Period 1
COMPLETED
|
7
|
7
|
7
|
6
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
7
|
7
|
7
|
4
|
|
Period 2
COMPLETED
|
7
|
7
|
7
|
4
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
7
|
7
|
5
|
4
|
|
Period 3
COMPLETED
|
7
|
7
|
5
|
4
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
7
|
7
|
5
|
4
|
|
Period 4
COMPLETED
|
7
|
7
|
5
|
4
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Roflumilast and Donepezil to Reverse Scopolamine Induced Cognitive Deficits in Healthy Adults
Baseline characteristics by cohort
| Measure |
Sequence 1 (ABDC)
n=7 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period.
|
Sequence 2 (BCAD)
n=7 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period.
|
Sequence 3 (CDBA)
n=7 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period.
|
Sequence 4 (DACB)
n=6 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period.
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
31.9 years
STANDARD_DEVIATION 7.69 • n=5 Participants
|
28.4 years
STANDARD_DEVIATION 6.73 • n=7 Participants
|
34.1 years
STANDARD_DEVIATION 6.89 • n=5 Participants
|
29.8 years
STANDARD_DEVIATION 5.12 • n=4 Participants
|
31.1 years
STANDARD_DEVIATION 6.71 • n=21 Participants
|
|
Gender
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Gender
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
6 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
2 participants
n=4 Participants
|
6 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4 participants
n=5 Participants
|
3 participants
n=4 Participants
|
15 participants
n=21 Participants
|
|
Region of Enrollment
United Kingdom
|
7 participants
n=5 Participants
|
7 participants
n=7 Participants
|
7 participants
n=5 Participants
|
6 participants
n=4 Participants
|
27 participants
n=21 Participants
|
|
Height
|
178.7 cm
STANDARD_DEVIATION 6.65 • n=5 Participants
|
177.3 cm
STANDARD_DEVIATION 6.87 • n=7 Participants
|
179.0 cm
STANDARD_DEVIATION 5.23 • n=5 Participants
|
174.5 cm
STANDARD_DEVIATION 5.79 • n=4 Participants
|
177.5 cm
STANDARD_DEVIATION 6.08 • n=21 Participants
|
|
Weight
|
82.16 kg
STANDARD_DEVIATION 9.759 • n=5 Participants
|
78.61 kg
STANDARD_DEVIATION 7.189 • n=7 Participants
|
81.53 kg
STANDARD_DEVIATION 4.476 • n=5 Participants
|
75.05 kg
STANDARD_DEVIATION 7.036 • n=4 Participants
|
79.50 kg
STANDARD_DEVIATION 7.473 • n=21 Participants
|
|
Body Mass Index (BMI)
|
25.76 kg/m^2
STANDARD_DEVIATION 3.173 • n=5 Participants
|
25.09 kg/m^2
STANDARD_DEVIATION 2.683 • n=7 Participants
|
25.49 kg/m^2
STANDARD_DEVIATION 1.670 • n=5 Participants
|
24.68 kg/m^2
STANDARD_DEVIATION 2.568 • n=4 Participants
|
25.27 kg/m^2
STANDARD_DEVIATION 2.462 • n=21 Participants
|
|
Smoking Classification
Never Smoked
|
7 participants
n=5 Participants
|
7 participants
n=7 Participants
|
6 participants
n=5 Participants
|
6 participants
n=4 Participants
|
26 participants
n=21 Participants
|
|
Smoking Classification
Current Smoker
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
|
Smoking Classification
Ex-smoker
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and 1 hour after scopolamine administration on Day 1 of each treatment period. Baseline is defined as the assessment 1 hour before roflumilast/donepezil administration (3 hours before scopolamine administration).Population: Participants from the Full Analysis Set with data available for analysis at the given time-point.
VRM measures the ability to encode and subsequently retrieve verbal information. This task begins with the first presentation phase in which 18 words are shown in turn on the screen. The participant is then asked to recall as many words as possible during the first immediate recall phase. The same 18 words are then shown in a second presentation phase which is followed by a second immediate recall phase. After a delay of approximately 20-30 minutes, a delayed recall stage is completed. The possible range of correct responses is 0 (worst) to 18 (best). Higher number of correct responses in the test indicates a better outcome. A negative change from baseline indicates a worsening of the score.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Change From Baseline in the Verbal Recall Memory (VRM) Total Number of Correct Responses for Delayed Recall at 1 Hour After Scopolamine Administration
|
-6.7 correct responses
Standard Deviation 3.02
|
-7.0 correct responses
Standard Deviation 3.33
|
-7.4 correct responses
Standard Deviation 3.62
|
-6.6 correct responses
Standard Deviation 2.68
|
PRIMARY outcome
Timeframe: Baseline and 1 hour after scopolamine administration on Day 1 of each treatment period.Population: Participants from the Full Analysis Set with data available for analysis at the given time-point.
VRM measures the ability to encode and subsequently retrieve verbal information. This task begins with the first presentation phase in which 18 words are shown in turn on the screen. The participant is then asked to recall as many words as possible during the first immediate recall phase. The possible range of correct responses is 0 (worst) to 18 (best). Higher number of correct responses in the test indicates a better outcome. A negative change from baseline indicates a worsening of the score.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Change From Baseline in the Verbal Recall Memory (VRM) Total Number of Correct Responses for Immediate Recall at 1 Hour After Scopolamine Administration
|
-9.8 correct responses
Standard Deviation 4.77
|
-7.7 correct responses
Standard Deviation 4.37
|
-10.6 correct responses
Standard Deviation 5.09
|
-7.7 correct responses
Standard Deviation 4.42
|
SECONDARY outcome
Timeframe: Baseline and 2 and 4 hours after scopolamine administration on Day 1 of each treatment period.Population: Participants from the Full Analysis Set with data available for analysis at the given time-point.
VRM measures the ability to encode and subsequently retrieve verbal information. This task begins with the first presentation phase in which 18 words are shown in turn on the screen. The participant is then asked to recall as many words as possible during the first immediate recall phase. The same 18 words are then shown in a second presentation phase which is followed by a second immediate recall phase. After a delay of approximately 20-30 minutes, a delayed recall stage is completed. The possible range of correct responses is 0 (worst) to 18 (best). Higher number of correct responses in the test indicates a better outcome. A negative change from baseline indicates a worsening of the score.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Change From Baseline in the Verbal Recall Memory (VRM) Total Number of Correct Responses for Immediate and Delayed Recall at 2 and 4 Hours After Scopolamine Administration
Delayed Recall: 4 hours post Scopolamine
|
-5.5 correct responses
Standard Deviation 2.64
|
-5.6 correct responses
Standard Deviation 3.34
|
-5.9 correct responses
Standard Deviation 2.98
|
-5.3 correct responses
Standard Deviation 2.50
|
|
Change From Baseline in the Verbal Recall Memory (VRM) Total Number of Correct Responses for Immediate and Delayed Recall at 2 and 4 Hours After Scopolamine Administration
Immediate Recall: 2 hours post Scopolamine
|
-10.1 correct responses
Standard Deviation 5.02
|
-7.3 correct responses
Standard Deviation 4.06
|
-9.9 correct responses
Standard Deviation 5.20
|
-6.5 correct responses
Standard Deviation 4.38
|
|
Change From Baseline in the Verbal Recall Memory (VRM) Total Number of Correct Responses for Immediate and Delayed Recall at 2 and 4 Hours After Scopolamine Administration
Immediate Recall: 4 hours post Scopolamine
|
-8.3 correct responses
Standard Deviation 5.64
|
-7.6 correct responses
Standard Deviation 4.59
|
-7.9 correct responses
Standard Deviation 4.50
|
-6.1 correct responses
Standard Deviation 4.23
|
|
Change From Baseline in the Verbal Recall Memory (VRM) Total Number of Correct Responses for Immediate and Delayed Recall at 2 and 4 Hours After Scopolamine Administration
Delayed Recall: 2 hours post Scopolamine
|
-6.3 correct responses
Standard Deviation 2.08
|
-5.6 correct responses
Standard Deviation 2.87
|
-6.8 correct responses
Standard Deviation 3.67
|
-5.9 correct responses
Standard Deviation 3.06
|
SECONDARY outcome
Timeframe: Baseline and at 1, 2 and 4 hours after scopolamine administration on Day 1 of each treatment period.Population: Participants from the Full Analysis Set with data available for analysis at the given time-point.
PAL assesses visuospatial associative learning and memory. Boxes are displayed on the screen and open in a randomised order to reveal a number of patterns. The patterns are then displayed in the middle of the screen, one at a time, and the participant must touch the box where the pattern was originally located. If the participant makes an error, the patterns are re-presented to remind the participant of their locations. If the participant has not responded correctly within six attempts, ie, one presentation and five re-presentations, the task is terminated. As the task progresses the difficulty level increases with the number of patterns to be remembered. For participants who fail to complete all levels, an adjusted total is calculated that takes into account errors predicted in the stages that were not attempted. The possible range for total errors is 0 (best) to 91 (worst). Fewer number of errors in the test indicates a better outcome.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Change From Baseline in the Paired Associates Learning (PAL) Total Number of Errors Adjusted at All Time-points Assessed After Scopolamine Administration
2 hours post Scopolamine
|
3.0 errors
Standard Deviation 10.11
|
3.0 errors
Standard Deviation 7.23
|
-0.7 errors
Standard Deviation 11.96
|
2.9 errors
Standard Deviation 9.12
|
|
Change From Baseline in the Paired Associates Learning (PAL) Total Number of Errors Adjusted at All Time-points Assessed After Scopolamine Administration
1 hour post Scopolamine
|
8.0 errors
Standard Deviation 12.73
|
11.5 errors
Standard Deviation 15.98
|
1.6 errors
Standard Deviation 10.70
|
7.5 errors
Standard Deviation 14.38
|
|
Change From Baseline in the Paired Associates Learning (PAL) Total Number of Errors Adjusted at All Time-points Assessed After Scopolamine Administration
4 hours post Scopolamine
|
2.3 errors
Standard Deviation 9.09
|
7.7 errors
Standard Deviation 16.00
|
0.2 errors
Standard Deviation 8.34
|
3.1 errors
Standard Deviation 9.31
|
SECONDARY outcome
Timeframe: Baseline and at 1, 2 and 4 hours after scopolamine administration on Day 1 of each treatment period.Population: Participants from the Full Analysis Set with data available for analysis at the given time-point.
RVP is a task of continuous performance and visual sustained attention. The task consists of a 2-minute practice stage and a 7-minute assessed stage. There is a white box in the centre of the screen in which single digits from 2 to 9 appear one at a time in a pseudo-random order at a rate of 100 digits per minute. Participants must detect target sequences of digits (2-4-6, 3-5-7, and 4-6-8) and touch a button when they see the last digit of a target sequence. Nine target sequences appear every 100 numbers. A prime (A') is a signal detection measure that reflects target sensitivity regardless of the participant's tendency, or bias, to respond. Detection sensitivity for RVP A' prime: 0 to 1. Lower numbers in the test indicates worsening in the performance.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Change From Baseline in the Rapid Visual Information Processing (RVP) A Prime Signal Detection at All Time-points Assessed After Scopolamine Administration
1 hour post Scopolamine
|
-0.0184 unitless
Standard Deviation 0.03206
|
-0.0107 unitless
Standard Deviation 0.03661
|
-0.0290 unitless
Standard Deviation 0.03090
|
-0.0157 unitless
Standard Deviation 0.03742
|
|
Change From Baseline in the Rapid Visual Information Processing (RVP) A Prime Signal Detection at All Time-points Assessed After Scopolamine Administration
2 hours post Scopolamine
|
-0.0297 unitless
Standard Deviation 0.03799
|
-0.0151 unitless
Standard Deviation 0.03249
|
-0.0315 unitless
Standard Deviation 0.03810
|
-0.0282 unitless
Standard Deviation 0.04667
|
|
Change From Baseline in the Rapid Visual Information Processing (RVP) A Prime Signal Detection at All Time-points Assessed After Scopolamine Administration
4 hours post Scopolamine
|
-0.0201 unitless
Standard Deviation 0.03972
|
-0.0106 unitless
Standard Deviation 0.02948
|
-0.0227 unitless
Standard Deviation 0.03534
|
-0.0114 unitless
Standard Deviation 0.03530
|
SECONDARY outcome
Timeframe: Baseline and at 1, 2 and 4 hours after scopolamine administration on Day 1 of each treatment period.Population: Participants from the Full Analysis Set with data available for analysis at the given time-point.
RVP is a task of continuous performance and visual sustained attention. The task consists of a 2-minute practice stage and a 7-minute assessed stage. There is a white box in the centre of the screen in which single digits from 2 to 9 appear one at a time in a pseudo-random order at a rate of 100 digits per minute. Participants must detect target sequences of digits (2-4-6, 3-5-7, and 4-6-8) and touch a button when they see the last digit of a target sequence. Nine target sequences appear every 100 numbers. Assessment will be based on a median latency. The possible range for RVP median latency is 100 (worst) to 1900 (best). Higher number in the test indicates a better outcome. "Median latency" is a measure captured by computerized test measure and given as "one" time value (between 100 and 1900). The "mean" of these values is presented.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Change From Baseline in the Rapid Visual Information Processing (RVP) Median Latency at All Time-points Assessed After Scopolamine Administration
1 hour post Scopolamine
|
10.63 msec
Standard Deviation 39.631
|
-7.35 msec
Standard Deviation 36.659
|
5.62 msec
Standard Deviation 36.538
|
2.59 msec
Standard Deviation 42.550
|
|
Change From Baseline in the Rapid Visual Information Processing (RVP) Median Latency at All Time-points Assessed After Scopolamine Administration
2 hours post Scopolamine
|
10.83 msec
Standard Deviation 45.635
|
-4.89 msec
Standard Deviation 42.713
|
10.62 msec
Standard Deviation 40.063
|
0.13 msec
Standard Deviation 55.005
|
|
Change From Baseline in the Rapid Visual Information Processing (RVP) Median Latency at All Time-points Assessed After Scopolamine Administration
4 hours post Scopolamine
|
13.13 msec
Standard Deviation 42.087
|
-5.39 msec
Standard Deviation 33.696
|
3.90 msec
Standard Deviation 39.485
|
-8.98 msec
Standard Deviation 41.002
|
SECONDARY outcome
Timeframe: Baseline and at 1, 2 and 4 hours after scopolamine administration on Day 1 of each treatment period.Population: Participants from the Full Analysis Set with data available for analysis at the given time-point.
SWM assesses the ability to retain spatial information and manipulate it in working memory. In this task, colored boxes are shown on the screen, and participants must search for blue tokens by touching the colored boxes to open them. When the blue token has been found the participant has to place the token in the black column ('home') on the right-hand side of the screen by touching this area. The participant must not return to a box where a token has previously been found. The task becomes more difficult as the number of boxes increases (one trial at each of 6-box and 8-box stages; three trials at each of 10-box and 12-box stages). Between Errors is the total number of times the participant revisits a box in which a token has previously been found in the same problem. The possible range of errors is 0 (best) to 1040 (worst). Lower number of errors in the test indicates a better outcome.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Change From Baseline in the Spatial Working Memory (SWM) Total Number of Between Errors at the 10-Box Stage and the 12-Box Stage at All Time-points Assessed After Scopolamine Administration
1 hour post Scopolamine
|
23.8 errors
Standard Deviation 36.96
|
25.7 errors
Standard Deviation 27.77
|
31.7 errors
Standard Deviation 22.66
|
16.5 errors
Standard Deviation 22.87
|
|
Change From Baseline in the Spatial Working Memory (SWM) Total Number of Between Errors at the 10-Box Stage and the 12-Box Stage at All Time-points Assessed After Scopolamine Administration
2 hours post Scopolamine
|
28.4 errors
Standard Deviation 22.57
|
13.4 errors
Standard Deviation 27.47
|
29.6 errors
Standard Deviation 23.88
|
18.2 errors
Standard Deviation 22.18
|
|
Change From Baseline in the Spatial Working Memory (SWM) Total Number of Between Errors at the 10-Box Stage and the 12-Box Stage at All Time-points Assessed After Scopolamine Administration
4 hours post Scopolamine
|
31.1 errors
Standard Deviation 29.88
|
19.7 errors
Standard Deviation 25.46
|
32.8 errors
Standard Deviation 26.62
|
7.7 errors
Standard Deviation 21.09
|
SECONDARY outcome
Timeframe: Day 1 up to Day 95Population: Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as any adverse event, regardless of relationship to study drug that occurs or worsens after the first dose of study drug and no more than 14 days after the last dose of study drug.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Percentage of Participants Who Experience at Least 1 Treatment Emergent Adverse Event (TEAE)
|
30.4 percentage of participants
|
65.2 percentage of participants
|
24.0 percentage of participants
|
51.9 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 95Population: Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
The percentage of participants with any markedly abnormal standard safety laboratory values, including hematology, serum chemistries, and urinalysis. LLN=lower limit of normal. ULN=upper limit of normal.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Hematocrit <0.8 x LLN (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Hematocrit >1.2 x ULN (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Platelet Count <75 x 10^3/μL (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Aspartate Aminotransferase >3xULN
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Hemoglobin <0.8 x LLN (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Hemoglobin >1.2 x ULN (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Platelet Count >600 x 10^3/μL (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Red Blood Cells <0.8 x LLN (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Red Blood Cells >1.2 x ULN (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
White Blood Cells <0.5 x LLN (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
White Blood Cells >1.5 x ULN (n=22,23,25,27)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Alanine Aminotransferase >3 x ULN
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Albumin <2.5 g/dL
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Alkaline Phosphatase >3 x ULN
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Blood Urea Nitrogen >10.7 mmol/L
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Calcium <1.75 mmol/L
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Calcium >2.88 mmol/L
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Creatine Kinase >5 x ULN
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Creatinine >2.0 mg/dL
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Gamma Glutamyl Transpeptidase >3xULN
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Potassium <3.0 mmol/L
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Potassium >6.0 mmol/L
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Sodium <130 mmol/L
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Sodium >150 mmol/L
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Total Bilirubin >2.0 mg/dL
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Total Protein <0.8 x LLN
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
Total Protein >1.2 x ULN
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 95Population: Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
The percentage of participants who meet markedly abnormal criteria for vital signs, including oral body temperature, respiration rate, pulse, and resting blood pressure and after standing.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements at Least Once Post-dose
Pulse <50 bpm
|
26.1 percentage of participants
|
21.7 percentage of participants
|
28.0 percentage of participants
|
33.3 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements at Least Once Post-dose
Pulse >120 bpm
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements at Least Once Post-dose
Systolic Blood Pressure <85 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements at Least Once Post-dose
Systolic Blood Pressure >180 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements at Least Once Post-dose
Diastolic Blood Pressure <50 mmHg
|
0 percentage of participants
|
8.7 percentage of participants
|
0 percentage of participants
|
11.1 percentage of participants
|
|
Percentage of Participants With Markedly Abnormal Vital Sign Measurements at Least Once Post-dose
Diastolic Blood Pressure >110 mmHg
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 95Population: Safety Analysis Set included all enrolled participants who received at least one dose of study drug.
The percentage of participants who meet markedly abnormal criteria specified by the protocol and statistical analysis plan=abnormal clinically significant.
Outcome measures
| Measure |
A: Placebo
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 Participants
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 Participants
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 Participants
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post-Dose
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
Adverse Events
A: Placebo
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
B: Donepezil 10 mg
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
C: Roflumilast Dose A
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
D: Roflumilast Dose A + Donepezil 10 mg
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
A: Placebo
n=23 participants at risk
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 participants at risk
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 participants at risk
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 participants at risk
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Infections and infestations
Viral infection
|
4.3%
1/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/25 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Other adverse events
| Measure |
A: Placebo
n=23 participants at risk
Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
B: Donepezil 10 mg
n=23 participants at risk
Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
C: Roflumilast Dose A
n=25 participants at risk
Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
D: Roflumilast Dose A + Donepezil 10 mg
n=27 participants at risk
Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1 in any of the 4 treatment periods.
|
|---|---|---|---|---|
|
Nervous system disorders
Dizziness
|
26.1%
6/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
13.0%
3/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
12.0%
3/25 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
11.1%
3/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Dry mouth
|
17.4%
4/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.7%
2/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.0%
2/25 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
11.1%
3/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
13.0%
3/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/25 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
18.5%
5/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Eye disorders
Vision blurred
|
4.3%
1/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
13.0%
3/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.0%
2/25 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
7.4%
2/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Headache
|
4.3%
1/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/25 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
7.4%
2/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
8.7%
2/23 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/25 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to ).
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
AstraZeneca Clinical Study Information Center
AstraZeneca
Phone: 1-877-240-9479
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
- Publication restrictions are in place
Restriction type: OTHER