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Clinical Trial Results:
STUDY OF ATTENTION AND IMPULSIVITY IN HEALTHY HUMAN VOLUNTEERS

Summary
EudraCT number	2018-003271-35
Trial protocol	DK
Global end of trial date	18 Dec 2019

Results information
Results version number	v1(current)
This version publication date	25 Sep 2021
First version publication date	25 Sep 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

KU-AIM-01-2018

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

University of Copenhagen

Sponsor organisation address

Øster Farimagsgade 2A, Copenhagen, Denmark, 1353

Public contact

Jon Lansner, University of Copenhagen, 45 61668876, jl@psy.ku.dk

Scientific contact

Jon Lansner , University of Copenhagen, 45 61668876, jl@psy.ku.dk

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Dec 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

18 Dec 2019

Global end of trial reached?

Yes

Global end of trial date

18 Dec 2019

Was the trial ended prematurely?

Main objective of the trial

The aim of this study is to investigate in young, healthy participants whether and to what degree single doses of methylphenidate, atomoxetine, amphetamine, and modafinil: a) enhance the TVA visual speed (C) and Visual Short Term Memory (VSTM) storage capacity (K) parameters, b) produce a reduction on commission and omission errors, and improvements in d’, reaction times and correct responses on the Conners CPT, and c) whether objectively measured changes in visual perceptual speed are associated with changes in subjective alertness and pleasantness of the task.

Protection of trial subjects

Participants will have no history of psychiatric, neurological or cardiovascular illness, no history of drug addiction. No pregnant or breastfeeding woman will be included. A pregnancy test will be done during the interview to avoid the inclusion of pregnant women. Women will be asked to follow any of the next contraception measures that have been considered acceptable by the CTFG. Subjects who are lactose intolerant or show any allergies to the excipients/active ingredients used in the administered drugs will not be included. Participants will have had no recreational use of psychostimulants in the last 3 months. Subject with a body mass index smaller than 18 or larger than 30 will be excluded for pharmacological safety and efficacy concerns. Risk of side-effects is minimized by screening for psychiatric conditions using the MINI interview, by performing an electrocardiogram, and by measuring the blood pressure before and after the intervention. A medical emergency procedure protocol provided by the Capital Region of Denmark and the continuous presence of a doctor will ensure the most efficient handling of any unexpected side effects. The level of Investigational Medicinal Product (IMP) accountability undertaken should decrease the risk of treatment mishandling and ensure that adequate treatment is provided to the participants. The extent of drug accountability documentation has been considered adequate to ensure the integrity of the trial data and the safety of the participants. There is no risk associated to the cognitive testing used for this study, although it may be accompanied by slight fatigue. Participants will not be allowed to drive/ride after testing. Subject may get monetary compensation for their use of public transportation. Skilled and experience professionals will be responsible for blood sampling, thus minimizing any potential discomfort. After drug administration, a light meal will be provided to decrease potential nausea.

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Feb 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Denmark: 104

Worldwide total number of subjects

104

EEA total number of subjects

104

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

104

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Recruitment will happen in the Copenhagen area using online advertisement and posters in study halls.

Screening details

Screening is conducted via interviews, tests and questionnaires prior to testing

Number of subjects started

104

Number of subjects completed

Reason: Number of subjects

History of psychiatric illness: 1

Reason: Number of subjects

Cardiovascular condition: 3

Reason: Number of subjects

major vision impairment: 1

Period 1 title

AIM-C (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

To ensure that the administrator of the task does not know which treatment is given to each participant, electronic documents containing such information will be stored separately from the administration schema. This will be part of the randomization and blinding of treatments/participants. A collaboration with professionals from H. Lundbeck A/S has been established to optimize and ensure the quality of this process.

Are arms mutually exclusive

Yes

AIM-C Part A

Arm description

Part A will be conducted on a different sample than Part B. The pharmacological tools to be used in this second study will be methylphenidate and atomoxetine. The general design for Part A is a double blind, placebo-controlled, within-subject, counter-balanced investigation. Each participant is tested in five separate sessions for methylphenidate and atomoxetine (low and high doses of each), and for placebo, allowing for within-subject comparisons. Before each experimental session, participants are given a high or a low dose of the drugs or placebo. The different doses will allow for analyses of dose-response relationships of the cognitive effects of the drugs. A diagram-balanced Latin square design will be used to achieve counterbalanced effects, so that each of the possible treatment sequences will be used. In all sessions, participants will be tested on both the Combi-TVA and the Conners CPT when the effect of the drug can be assumed to have reached its maximal level

Arm type

Experimental

Investigational medicinal product name

Methylphenidate

Investigational medicinal product code

N06BA04

Other name

Ritalin, Concerta

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Methylphenidate 20mg (2x10mg). Vendor: Alternova. Package Name: Methylphenidat “Alternova”, tabletter Methylphenidate 40mg (2x20mg). Vendor: Alternova. Package Name: Methylphenidat “Alternova”, tabletter To ensure the placebo and drugs match the same sensory specifications over-encapsulation will be chosen as a blinding method. The process of over-encapsulation, together with the purchase of drugs, will be done in in collaboration with Capital Region Pharmacy.

Investigational medicinal product name

Atomoxetine

Investigational medicinal product code

N06BA09

Other name

Strattera, (R)-N-Methyl-3-phenyl-3-(o-tolyloxy)propan-1-amine

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Atomoxetine 40mg (1x40mg). Vendor: Actavis. Package name: Atomoxetin “Actavis” hårde kapsler Atomoxetine 60mg (1x60mg). Vendor: Actavis. Package name: Atomoxetin “Actavis” hårde kapsler To ensure the placebo and drugs match the same sensory specifications over-encapsulation will be chosen as a blinding method. The process of over-encapsulation, together with the purchase of drugs, will be done in in collaboration with Capital Region Pharmacy.

AIM-C Part B

Arm description

Part B will be conducted on a different sample. The pharmacological tools to be used in this second study will be dexamphetamine and modafinil. The general design for Part B is a double blind, placebo-controlled, within-subject, counter-balanced investigation. Each participant is tested in five separate sessions for dexamphetamine and modafinil (low and high doses of each), and for placebo, allowing for within-subject comparisons. Before each experimental session, participants are given a high or a low dose of the drugs or placebo. The different doses will allow for analyses of dose-response relationships of the cognitive effects of the drugs. A diagram-balanced Latin square design will be used to achieve counterbalanced effects, so that each of the possible treatment sequences will be used. In all sessions, participants will be tested on both the Combi-TVA and the Conners CPT when the effect of the drug can be assumed to have reached its maximal level

Arm type

Experimental

Investigational medicinal product name

Modafinil

Investigational medicinal product code

N06BA07

Other name

Provigil, Alertec, Modavigil, CRL-40476, Diphenylmethylsulfinylacetamide

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Modafinil 200 mg (2x100 mg), Vendor: Orion Corporation. Package name: Modafinil “Orion”, tabletter Modafinil 400 mg (2x200 mg), Vendor: Orion Corporation. Package name: Modafinil “Orion”, tabletter To ensure the placebo and drugs match the same sensory specifications over-encapsulation will be chosen as a blinding method. The process of over-encapsulation, together with the purchase of drugs, will be done in in collaboration with Capital Region Pharmacy.

Investigational medicinal product name

Dexamphetamine

Investigational medicinal product code

N06BA02

Other name

Dexedrine, DextroStat, Metamina, Attentin, Zenzedi, ProCentra, Amfexa, D-Amphetamine

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Dexamphetamine 10mg (1x10mg), Vendor: Orifarm A7S. Package name: Attentin, tabletter (Orifarm A/S) Dexamphetamine 10mg, (1x20mg) Vendor: Orifarm A7S. Package name: Attentin, tabletter (Orifarm A/S) To ensure the placebo and drugs match the same sensory specifications over-encapsulation will be chosen as a blinding method. This is a common and effective solution to blinding solid oral formulations . The process of over-encapsulation, together with the purchase of drugs, will be done in in collaboration with Capital Region Pharmacy

Number of subjects in period 1 ^[1]	AIM-C Part A	AIM-C Part B
Started	44	55
Attended visit 1	34	48
Completed	29	37
Not completed	15	18
Illness >2 weeks	2	3
Logistical reasons	6	-
Did not obtain contact lenses	1	-
Side-effects of the drugs	1	-
Inclusion criteria no longer met	2	-
Side-effects of the treatment	-	3
Personal or logistic reasons	-	9
No response after contact	3	3

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 104 subjects attended the screening visit during the pre-assignment period, however 5 subjects did not meet the criteria for inclusion, and thus only 99 were enrolled in the study, as described. This creates a confusion in this registration system, as the 104 are counted as part of the baseline period, when in fact only 99 were included.

Baseline characteristics

Top of page

Reporting group title

AIM-C

Reporting group description

Reporting group values	AIM-C	Total
Number of subjects	99	99
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	99	99
From 65-84 years	0	0
85 years and over	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	24.19 ( 2.79 )	-
Gender categorical
Units: Subjects
Female	67	67
Male	32	32
ASRS - Adult Self-Report Scale questionnaire
Number of marks in the darkly shaded boxes in the first 6 questions, indicating potential adult ADHD. Kessler, R. C., Adler, L. A., Gruber, M. J., Sarawate, C. A., Spencer, T., & Van Brunt, D. L. (2007). Validity of the World Health Organization Adult ADHD Self‐Report Scale (ASRS) Screener in a representative sample of health plan members. International journal of methods in psychiatric research, 16(2), 52-65.
Units: Part A score (0-6)
arithmetic mean (standard deviation)	1.48 ( 1.42 )	-

Subject analysis set title

Part A - Attended first visit

Subject analysis set type

Full analysis

Subject analysis set description

Only subjects that had attended atleast one visit was included in the analysis.

Subject analysis set title

Part B - Attended first visit

Subject analysis set type

Full analysis

Subject analysis set description

Participants in Part B

Subject analysis set title

Part A - Placebo

Subject analysis set type

Full analysis

Subject analysis set description

The placebo condition for participants in Part A

Subject analysis set title

Part A - MPH20

Subject analysis set type

Full analysis

Subject analysis set description

The methylphenidate 20mg condition for participants in Part A

Subject analysis set title

Part A - MPH40

Subject analysis set type

Full analysis

Subject analysis set description

The methylphenidate 40mg condition for participants in Part A

Subject analysis set title

Part A - ATX40

Subject analysis set type

Full analysis

Subject analysis set description

The atomoxetine 40mg condition for participants in Part A

Subject analysis set title

Part A - ATX60

Subject analysis set type

Full analysis

Subject analysis set description

The atomoxetine 60mg condition for participants in Part A

Subject analysis set title

Part B - AMPH10

Subject analysis set type

Full analysis

Subject analysis set description

The dexamphetamine 10mg condition for participants in Part B

Subject analysis set title

Part B - AMPH20

Subject analysis set type

Full analysis

Subject analysis set description

The dexamphetamine 20mg condition for participants in Part B

Subject analysis set title

Part B - MOD200

Subject analysis set type

Full analysis

Subject analysis set description

The modafinil 200mg condition for participants in Part B

Subject analysis set title

Part B - MOD400

Subject analysis set type

Full analysis

Subject analysis set description

The modafinil 400mg condition for participants in Part B

Subject analysis set title

Part B - Placebo

Subject analysis set type

Full analysis

Subject analysis set description

The placebo condition for participants in Part B

Subject analysis sets values	Part A - Attended first visit	Part B - Attended first visit	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects	34	48	32	32	30	30	30	41	41	43	44	44
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)	34	48	32	32	30	30	30	41	41	43	44	44
From 65-84 years
85 years and over
Age continuous
Units: years
arithmetic mean (standard deviation)	24.24 ( 2.73 )	23.94 ( 2.36 )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )
Gender categorical
Units: Subjects
Female	26	30
Male	8	18
ASRS - Adult Self-Report Scale questionnaire
Number of marks in the darkly shaded boxes in the first 6 questions, indicating potential adult ADHD. Kessler, R. C., Adler, L. A., Gruber, M. J., Sarawate, C. A., Spencer, T., & Van Brunt, D. L. (2007). Validity of the World Health Organization Adult ADHD Self‐Report Scale (ASRS) Screener in a representative sample of health plan members. International journal of methods in psychiatric research, 16(2), 52-65.
Units: Part A score (0-6)
arithmetic mean (standard deviation)	1.56 ( 1.46 )	1.43 ( 1.43 )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )

End points

Top of page

Reporting group title

AIM-C Part A

Reporting group description

Reporting group title

AIM-C Part B

Reporting group description

Subject analysis set title

Part A - Attended first visit

Subject analysis set type

Full analysis

Subject analysis set description

Only subjects that had attended atleast one visit was included in the analysis.

Subject analysis set title

Part B - Attended first visit

Subject analysis set type

Full analysis

Subject analysis set description

Participants in Part B

Subject analysis set title

Part A - Placebo

Subject analysis set type

Full analysis

Subject analysis set description

The placebo condition for participants in Part A

Subject analysis set title

Part A - MPH20

Subject analysis set type

Full analysis

Subject analysis set description

The methylphenidate 20mg condition for participants in Part A

Subject analysis set title

Part A - MPH40

Subject analysis set type

Full analysis

Subject analysis set description

The methylphenidate 40mg condition for participants in Part A

Subject analysis set title

Part A - ATX40

Subject analysis set type

Full analysis

Subject analysis set description

The atomoxetine 40mg condition for participants in Part A

Subject analysis set title

Part A - ATX60

Subject analysis set type

Full analysis

Subject analysis set description

The atomoxetine 60mg condition for participants in Part A

Subject analysis set title

Part B - AMPH10

Subject analysis set type

Full analysis

Subject analysis set description

The dexamphetamine 10mg condition for participants in Part B

Subject analysis set title

Part B - AMPH20

Subject analysis set type

Full analysis

Subject analysis set description

The dexamphetamine 20mg condition for participants in Part B

Subject analysis set title

Part B - MOD200

Subject analysis set type

Full analysis

Subject analysis set description

The modafinil 200mg condition for participants in Part B

Subject analysis set title

Part B - MOD400

Subject analysis set type

Full analysis

Subject analysis set description

The modafinil 400mg condition for participants in Part B

Subject analysis set title

Part B - Placebo

Subject analysis set type

Full analysis

Subject analysis set description

The placebo condition for participants in Part B

Primary: d-prime CPT

Top of page

End point title

d-prime CPT

End point description

d-prime of the CPT task

End point type

Primary

End point timeframe

Effects of MPH and ATX on the CPT were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[1]	32 ^[2]	30 ^[3]	30 ^[4]	30 ^[5]	41 ^[6]	41 ^[7]	43 ^[8]	44 ^[9]	44 ^[10]
Units: standard deviation
arithmetic mean (standard error)	-3.24 ( 0.91 )	-3.53 ( 0.59 )	-3.42 ( 0.66 )	-3.19 ( 0.9 )	-3.18 ( 0.73 )	-3.50 ( 0.74 )	-3.65 ( 0.65 )	-3.45 ( 0.67 )	-3.51 ( 0.58 )	-3.22 ( 0.62 )

Notes
[1] - The placebo condition for participants in Part A
[2] - This was a cross over design
[3] - This was a crossover design
[4] - This was a crossover design
[5] - This was a crossover design
[6] - This was a crossover design
[7] - This was a crossover design
[8] - This was a crossover design
[9] - This was a crossover design
[10] - This was a crossover design

d-prime: Placebo - MPH20

Statistical analysis description

Difference between Placebo and MPH20 Evaluated via a linear mixed-effects model: [d-prime + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.01

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.07

Variability estimate

Standard error of the mean

Dispersion value

0.1

d-prime: Placebo - MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [d-prime + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.1

d-prime: Placebo - ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [d-prime + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.55

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

0.27

Variability estimate

Standard error of the mean

Dispersion value

0.1

d-prime: Placebo - ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [d-prime + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.49

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.28

Variability estimate

Standard error of the mean

Dispersion value

0.1

d-prime: Placebo - AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [d-prime + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - AMPH10 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.09

d-prime: Placebo - AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [d-prime + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

-0.24

Variability estimate

Standard error of the mean

Dispersion value

0.09

d-prime: Placebo - MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [d-prime + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.016

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.08

d-prime: Placebo - MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [d-prime + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

-0.11

Variability estimate

Standard error of the mean

Dispersion value

0.08

Primary: C - CPT

Top of page

End point title

C - CPT

End point description

Decision criterion for the CPT

End point type

Primary

End point timeframe

Effects of MPH and ATX on the CPT were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[11]	32 ^[12]	30 ^[13]	30 ^[14]	30 ^[15]	41 ^[16]	41 ^[17]	43 ^[18]	44 ^[19]	44 ^[20]
Units: standard deviation
arithmetic mean (standard error)	-0.86 ( 0.32 )	-0.91 ( 0.21 )	-0.87 ( 0.29 )	-0.85 ( 0.37 )	-0.84 ( 0.34 )	-0.96 ( 0.24 )	-0.92 ( 0.21 )	-0.92 ( 0.22 )	-0.95 ( 0.2 )	-0.94 ( 0.25 )

Notes
[11] - This was performed in a crossover design
[12] - This was performed in a crossover design
[13] - This was performed in a crossover design
[14] - This was performed in a crossover design
[15] - This was performed in a crossover design
[16] - This was performed in a crossover design
[17] - This was performed in a crossover design
[18] - This was performed in a crossover design
[19] - This was performed in a crossover design
[20] - This was performed in a crossover design

C-CPT: Placebo - MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.34

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.153

upper limit

0.053

Variability estimate

Standard error of the mean

Dispersion value

0.05

C-CPT: Placebo - MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.87

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.097

upper limit

0.115

Variability estimate

Standard error of the mean

Dispersion value

0.05

C-CPT: Placebo - ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.79

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.119

Variability estimate

Standard error of the mean

Dispersion value

0.05

d-prime: Placebo - ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.74

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.088

upper limit

0.123

Variability estimate

Standard error of the mean

Dispersion value

0.05

C-CPT: Placebo - AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.056

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.082

upper limit

0.044

Variability estimate

Standard error of the mean

Dispersion value

0.03

C-CPT: Placebo - AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.63

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.048

upper limit

0.078

Variability estimate

Standard error of the mean

Dispersion value

0.03

C-CPT: Placebo - MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.58

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.045

upper limit

0.079

Variability estimate

Standard error of the mean

Dispersion value

0.03

C-CPT: Placebo - MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD400 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.74

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.071

upper limit

0.051

Variability estimate

Standard error of the mean

Dispersion value

0.03

Primary: HRT - CPT

Top of page

End point title

HRT - CPT

End point description

Hit Reaction Time in the Continuous Performance Task

End point type

Primary

End point timeframe

Effects of MPH and ATX on the CPT were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[21]	32 ^[22]	30 ^[23]	30 ^[24]	30 ^[25]	41 ^[26]	41 ^[27]	43 ^[28]	44 ^[29]	44 ^[30]
Units: milliseconds
arithmetic mean (standard error)	353.90 ( 50.21 )	338.43 ( 38.57 )	342.95 ( 40.98 )	354.71 ( 51.52 )	357.43 ( 56.65 )	328.47 ( 32.65 )	333.48 ( 34.34 )	332.9 ( 33.49 )	327.97 ( 31.12 )	338.03 ( 37.51 )

Notes
[21] - This was performed in a cross-over design
[22] - This was performed in a cross-over design
[23] - This was performed in a cross-over design
[24] - This was performed in a cross-over design
[25] - This was performed in a cross-over design
[26] - This was performed in a cross-over design
[27] - This was performed in a cross-over design
[28] - This was performed in a cross-over design
[29] - This was performed in a cross-over design
[30] - This was performed in a cross-over design

HRT-CPT: Placebo - MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-15.64

Confidence interval

level

95%

sides

2-sided

lower limit

-23.929

upper limit

-7.357

Variability estimate

Standard error of the mean

Dispersion value

4.19

HRT-CPT: Placebo - MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-10.57

Confidence interval

level

95%

sides

2-sided

lower limit

-19.106

upper limit

-2.043

Variability estimate

Standard error of the mean

Dispersion value

4.32

HRT-CPT: Placebo - ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.94

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-8.804

upper limit

8.142

Variability estimate

Standard error of the mean

Dispersion value

4.29

HRT-CPT: Placebo - ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - ATX60 v Part A - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.72

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

-6.959

upper limit

10.084

Variability estimate

Standard error of the mean

Dispersion value

4.31

HRT-CPT: Placebo - AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-10.14

Confidence interval

level

95%

sides

2-sided

lower limit

-15.302

upper limit

-4.987

Variability estimate

Standard error of the mean

Dispersion value

2.62

HRT-CPT: Placebo - AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-8.37

Confidence interval

level

95%

sides

2-sided

lower limit

-13.523

upper limit

-3.207

Variability estimate

Standard error of the mean

Dispersion value

2.61

HRT-CPT: Placebo - MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.01

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.62

Confidence interval

level

95%

sides

2-sided

lower limit

-11.69

upper limit

-1.547

Variability estimate

Standard error of the mean

Dispersion value

2.57

HRT-CPT: Placebo - MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-12.53

Confidence interval

level

95%

sides

2-sided

lower limit

-17.542

upper limit

-7.515

Variability estimate

Standard error of the mean

Dispersion value

2.54

Primary: HRT.SD - CPT

Top of page

End point title

HRT.SD - CPT

End point description

The standard deviation of the Hit Reaction Time in the Continuous Performance Task

End point type

Primary

End point timeframe

Effects of MPH and ATX on the CPT were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[31]	32 ^[32]	30 ^[33]	30 ^[34]	30 ^[35]	41 ^[36]	41 ^[37]	43 ^[38]	44 ^[39]	44 ^[40]
Units: milliseconds
arithmetic mean (standard error)	0.2 ( 0.06 )	0.17 ( 0.04 )	0.17 ( 0.03 )	0.2 ( 0.06 )	0.2 ( 0.05 )	0.18 ( 0.05 )	0.17 ( 0.04 )	0.18 ( 0.04 )	0.17 ( 0.03 )	0.2 ( 0.05 )

Notes
[31] - Conducted in a cross-over design
[32] - Conducted in a cross-over design
[33] - Conducted in a cross-over design
[34] - Conducted in a cross-over design
[35] - Conducted in a cross-over design
[36] - Conducted in a cross-over design
[37] - Conducted in a cross-over design
[38] - Conducted in a cross-over design
[39] - Conducted in a cross-over design
[40] - Conducted in a cross-over design

HRT.SD - CPT: Placebo - MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT.SD + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.044

upper limit

-0.018

Variability estimate

Standard error of the mean

Dispersion value

0.01

HRT.SD - CPT: Placebo - MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT.SD + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

-0.023

Variability estimate

Standard error of the mean

Dispersion value

0.01

HRT.SD - CPT: Placebo - ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT.SD + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.64

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.016

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.01

HRT.SD - CPT: Placebo - ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT.SD + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.56

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.017

upper limit

0.009

Variability estimate

Standard error of the mean

Dispersion value

0.01

HRT.SD - CPT: Placebo - AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT.SD + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.005

HRT.SD - CPT: Placebo - AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT.SD + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.042

upper limit

-0.022

Variability estimate

Standard error of the mean

Dispersion value

0.005

HRT.SD - CPT: Placebo - MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT.SD + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.005

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.024

upper limit

-0.004

Variability estimate

Standard error of the mean

Dispersion value

0.005

HRT.SD - CPT: Placebo - MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [HRT.SD + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.035

upper limit

-0.016

Variability estimate

Standard error of the mean

Dispersion value

0.005

Primary: VAR - CPT

Top of page

End point title

VAR - CPT

End point description

Variability in hit reaction time between sub-blocks of the continuous performance test.

End point type

Primary

End point timeframe

Effects of MPH and ATX on the CPT were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[41]	32 ^[42]	30 ^[43]	30 ^[44]	30 ^[45]	41 ^[46]	41 ^[47]	43 ^[48]	44 ^[49]	44 ^[50]
Units: milliseconds
arithmetic mean (standard error)	0.05 ( 0.02 )	0.04 ( 0.01 )	0.04 ( 0.01 )	0.05 ( 0.02 )	0.05 ( 0.02 )	0.05 ( 0.03 )	0.04 ( 0.02 )	0.05 ( 0.02 )	0.04 ( 0.01 )	0.05 ( 0.02 )

Notes
[41] - Conducted wit a cross-over design
[42] - Conducted wit a cross-over design
[43] - Conducted wit a cross-over design
[44] - Conducted wit a cross-over design
[45] - Conducted wit a cross-over design
[46] - Conducted wit a cross-over design
[47] - Conducted with a cross-over design
[48] - Conducted with a cross-over design
[49] - Conducted with a cross-over design
[50] - Conducted with a cross-over design

VAR - CPT: MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [VAR + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.07

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.014

upper limit

0.001

Variability estimate

Standard error of the mean

Dispersion value

CAR - CPT: MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [VAR + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.016

upper limit

-0.001

Variability estimate

Standard error of the mean

Dispersion value

VAR - CPT: ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [VAR + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.69

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.006

upper limit

0.009

Variability estimate

Standard error of the mean

Dispersion value

VAR - CPT: ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [VAR + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.5

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.005

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

VAR - CPT: AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [VAR + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.07

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.005

Confidence interval

level

95%

sides

2-sided

lower limit

-0.011

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.003

VAR - CPT: AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [VAR + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.011

Confidence interval

level

95%

sides

2-sided

lower limit

-0.017

upper limit

-0.005

Variability estimate

Standard error of the mean

Dispersion value

0.003

VAR - CPT: MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [VAR + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.03

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.006

Confidence interval

level

95%

sides

2-sided

lower limit

-0.012

upper limit

-0.001

Variability estimate

Standard error of the mean

Dispersion value

0.003

VAR - CPT: MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [VAR + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.012

Confidence interval

level

95%

sides

2-sided

lower limit

-0.017

upper limit

-0.005

Variability estimate

Standard error of the mean

Dispersion value

0.003

Primary: BLKCH - CPT

Top of page

End point title

BLKCH - CPT

End point description

Variations in hit reaction time between blocks in the continuous performance task

End point type

Primary

End point timeframe

Effects of MPH and ATX on the CPT were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[51]	32 ^[52]	30 ^[53]	30 ^[54]	30 ^[55]	41 ^[56]	41 ^[57]	43 ^[58]	44 ^[59]	44 ^[60]
Units: milliseconds
arithmetic mean (standard error)	0.006 ( 0.004 )	0.001 ( 0.003 )	0.01 ( 0.002 )	0.013 ( 0.004 )	0.014 ( 0.004 )	0.002 ( 0.002 )	0.005 ( 0.001 )	0.002 ( 0.002 )	0.009 ( 0.002 )	0.0043 ( 0.002 )

Notes
[51] - Conducted using a cross-over design
[52] - Conducted using a cross-over design
[53] - Conducted using a cross-over design
[54] - Conducted using a cross-over design
[55] - Conducted using a cross-over design
[56] - Conducted using a cross-over design
[57] - Conducted using a cross-over design
[58] - Conducted using a cross-over design
[59] - Conducted using a cross-over design
[60] - Conducted using a cross-over design

BLKCH - CPT: MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [BLKCH + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.17

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.012

upper limit

0.002

Variability estimate

Standard error of the mean

Dispersion value

BLKCH - CPT: MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [BLKCH + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.25

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.003

upper limit

0.012

Variability estimate

Standard error of the mean

Dispersion value

BLKCH - CPT: ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [BLKCH + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.1

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.001

upper limit

0.014

Variability estimate

Standard error of the mean

Dispersion value

BLKCH - CPT: ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [BLKCH + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.08

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.001

upper limit

0.014

Variability estimate

Standard error of the mean

Dispersion value

BLKCH - CPT: AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [BLKCH + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - AMPH10 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.27

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.002

Confidence interval

level

95%

sides

2-sided

lower limit

-0.007

upper limit

0.002

Variability estimate

Standard error of the mean

Dispersion value

0.002

BLKCH - CPT: AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [BLKCH + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.91

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.0003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.004

upper limit

0.005

Variability estimate

Standard error of the mean

Dispersion value

0.002

BLKCH - CPT: MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [BLKCH + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.24

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.007

upper limit

0.002

Variability estimate

Standard error of the mean

Dispersion value

0.002

BLKCH - CPT: MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [BLKCH + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD400 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.047

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.004

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.008

Variability estimate

Standard error of the mean

Dispersion value

0.002

Primary: ISI - CPT

Top of page

End point title

ISI - CPT

End point description

Variability in hit reaction time between different inter-stimulus interval conditions in the continuous performance task

End point type

Primary

End point timeframe

Effects of MPH and ATX on the CPT were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[61]	32 ^[62]	30 ^[63]	30 ^[64]	30 ^[65]	41 ^[66]	41 ^[67]	43 ^[68]	44 ^[69]	44 ^[70]
Units: milliseconds
arithmetic mean (standard error)	0.057 ( 0.006 )	0.048 ( 0.004 )	0.041 ( 0.004 )	0.049 ( 0.005 )	0.049 ( 0.004 )	0.043 ( 0.003 )	0.041 ( 0.003 )	0.052 ( 0.004 )	0.046 ( 0.004 )	0.051 ( 0.005 )

Notes
[61] - This was conducted using a cross over design
[62] - This was conducted using a cross over design
[63] - This was conducted using a cross over design
[64] - This was conducted using a cross over design
[65] - This was conducted using a cross over design
[66] - This was conducted using a cross over design
[67] - This was conducted using a cross over design
[68] - This was conducted using a cross over design
[69] - This was conducted using a cross over design
[70] - This was conducted using a cross over design

ISI - CPT: MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [ISI + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.018

upper limit

-0.002

Variability estimate

Standard error of the mean

Dispersion value

ISI - CPT: MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [ISI + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.02

upper limit

-0.007

Variability estimate

Standard error of the mean

Dispersion value

ISI - CPT: ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [ISI + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.16

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.002

Variability estimate

Standard error of the mean

Dispersion value

ISI - CPT: ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [ISI + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.096

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.016

upper limit

0.001

Variability estimate

Standard error of the mean

Dispersion value

ISI - CPT: AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [ISI + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.009

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.008

Confidence interval

level

95%

sides

2-sided

lower limit

-0.015

upper limit

-0.002

Variability estimate

Standard error of the mean

Dispersion value

0.003

ISI - CPT: AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [ISI + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - AMPH20 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.017

upper limit

-0.005

Variability estimate

Standard error of the mean

Dispersion value

0.003

ISI - CPT: MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [ISI + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD200 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.41

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.003

upper limit

0.008

Variability estimate

Standard error of the mean

Dispersion value

0.003

ISI - CPT: MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [ISI + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD400 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.14

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.005

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.001

Variability estimate

Standard error of the mean

Dispersion value

0.003

Primary: K - TVA

Top of page

End point title

K - TVA

End point description

Maximal number of letters contained in Visual Short Term Memory

End point type

Primary

End point timeframe

Effects of MPH and ATX on the TVA were tested 90 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the TVA were tested 120 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[71]	32 ^[72]	30 ^[73]	30 ^[74]	30 ^[75]	41 ^[76]	41 ^[77]	43 ^[78]	44 ^[79]	44 ^[80]
Units: Letters
arithmetic mean (standard error)	3.36 ( 0.64 )	3.31 ( 0.54 )	3.42 ( 0.55 )	3.30 ( 0.66 )	3.24 ( 0.57 )	3.68 ( 0.59 )	3.71 ( 0.68 )	3.61 ( 0.62 )	3.66 ( 0.62 )	3.66 ( 0.63 )

Notes
[71] - Conducted in a cross over design
[72] - Conducted in a cross over design
[73] - Conducted in a cross over design
[74] - Conducted in a cross over design
[75] - Conducted in a cross over design
[76] - Conducted in a cross over design
[77] - Conducted in a cross over design
[78] - Conducted in a cross over design
[79] - Conducted in a cross over design
[80] - Conducted in a cross over design

K - TVA: MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [K + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.45

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.154

upper limit

0.068

Variability estimate

Standard error of the mean

Dispersion value

0.06

K - TVA: MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [K + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.12

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.233

upper limit

0.204

Variability estimate

Standard error of the mean

Dispersion value

0.06

K - TVA: ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [K + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.25

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.181

upper limit

0.047

Variability estimate

Standard error of the mean

Dispersion value

0.06

K - TVA: ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [K + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.05

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.231

upper limit

-0.002

Variability estimate

Standard error of the mean

Dispersion value

0.06

K - TVA: AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [K + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.59

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.147

upper limit

0.083

Variability estimate

Standard error of the mean

Dispersion value

0.07

K - TVA: AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [K + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.33

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.058

upper limit

0.171

Variability estimate

Standard error of the mean

Dispersion value

0.06

K - TVA: MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [K + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.33

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.168

upper limit

0.057

Variability estimate

Standard error of the mean

Dispersion value

0.06

K - TVA: MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [K + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD400 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.96

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.002

Confidence interval

level

95%

sides

2-sided

lower limit

-0.108

upper limit

0.114

Variability estimate

Standard error of the mean

Dispersion value

0.006

Primary: t0 - TVA

Top of page

End point title

t0 - TVA

End point description

The shortest exposure duration in which the participant can report atleast one letter

End point type

Primary

End point timeframe

Effects of MPH and ATX on the TVA were tested 90 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the TVA were tested 120 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[81]	32 ^[82]	30 ^[83]	30 ^[84]	30 ^[85]	41 ^[86]	41 ^[87]	43 ^[88]	44 ^[89]	44 ^[90]
Units: milliseconds
arithmetic mean (standard error)	17.421 ( 1.776 )	16.572 ( 1.719 )	15.076 ( 1.479 )	17.046 ( 1.874 )	18.328 ( 1.763 )	15.307 ( 1.652 )	16.777 ( 1.809 )	17.014 ( 1.854 )	16.698 ( 1.581 )	14.854 ( 1.15 )

Notes
[81] - This was conducted in a cross over design
[82] - This was conducted in a cross over design
[83] - This was conducted in a cross over design
[84] - This was conducted in a cross over design
[85] - This was conducted in a cross over design
[86] - This was conducted in a cross over design
[87] - This was conducted in a cross over design
[88] - This was conducted in a cross over design
[89] - This was conducted in a cross over design
[90] - This was conducted in a cross over design

t0 - TVA: MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [t0 + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - MPH20 v Part A - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.5

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-2.995

upper limit

1.467

Variability estimate

Standard error of the mean

Dispersion value

1.13

t0 - TVA: MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [t0 + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.07

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.12

Confidence interval

level

95%

sides

2-sided

lower limit

-4.392

upper limit

0.151

Variability estimate

Standard error of the mean

Dispersion value

1.15

t0 - TVA: ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [t0 + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.95

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-2.359

upper limit

2.205

Variability estimate

Standard error of the mean

Dispersion value

1.15

t0 - TVA: ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [t0 + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.27

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

-1.023

upper limit

3.569

Variability estimate

Standard error of the mean

Dispersion value

1.16

t0 - TVA: AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [t0 + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - AMPH10 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.66

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-1.501

upper limit

2.372

Variability estimate

Standard error of the mean

Dispersion value

0.98

t0 - TVA: AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [t0 + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.18

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

-0.612

upper limit

3.252

Variability estimate

Standard error of the mean

Dispersion value

0.98

t0 - TVA: MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [t0 + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD200 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.15

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.507

upper limit

3.294

Variability estimate

Standard error of the mean

Dispersion value

0.96

t0 - TVA: MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [t0 + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD400 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.042

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.066

upper limit

3.795

Variability estimate

Standard error of the mean

Dispersion value

0.95

Primary: C - TVA

Top of page

End point title

C - TVA

End point description

Visual Processing Speed in the Theory of VIsual Attention Test

End point type

Primary

End point timeframe

Effects of MPH and ATX on the TVA were tested 90 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the TVA were tested 120 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[91]	32 ^[92]	30 ^[93]	30 ^[94]	30 ^[95]	41 ^[96]	41 ^[97]	43 ^[98]	44 ^[99]	44 ^[100]
Units: letters pr second
arithmetic mean (standard error)	76.12 ( 31.95 )	84.32 ( 32.56 )	83.87 ( 31.97 )	80.85 ( 27.50 )	85.20 ( 28.31 )	125.33 ( 146.86 )	118.11 ( 155.35 )	105.72 ( 90.75 )	90 ( 40.37 )	92.64 ( 52.02 )

Notes
[91] - This was conducted in a cross over design
[92] - This was conducted in a cross over design
[93] - This was conducted in a cross over design
[94] - This was conducted in a cross over design
[95] - This was conducted in a cross over design
[96] - This was conducted in a cross over design
[97] - This was conducted in a cross over design
[98] - This was conducted in a cross over design
[99] - This was conducted in a cross over design
[100] - This was conducted in a cross over design

C- TVA: MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - MPH20 v Part A - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.11

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

7.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.796

upper limit

16.589

Variability estimate

Standard error of the mean

Dispersion value

4.65

C - TVA: MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.07

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.66

Confidence interval

level

95%

sides

2-sided

lower limit

-0.677

upper limit

18.005

Variability estimate

Standard error of the mean

Dispersion value

4.73

C- -TVA: ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.41

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.94

Confidence interval

level

95%

sides

2-sided

lower limit

-5.456

upper limit

13.331

Variability estimate

Standard error of the mean

Dispersion value

4.75

C - TVA: ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.06

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

9.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.312

upper limit

18.567

Variability estimate

Standard error of the mean

Dispersion value

4.78

C - TVA: AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

15.09

Confidence interval

level

95%

sides

2-sided

lower limit

6.443

upper limit

23.732

Variability estimate

Standard error of the mean

Dispersion value

4.38

C - TVA: AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.013

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

10.96

Confidence interval

level

95%

sides

2-sided

lower limit

2.331

upper limit

19.588

Variability estimate

Standard error of the mean

Dispersion value

4.38

C - TVA: MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.056

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

8.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.232

upper limit

16.744

Variability estimate

Standard error of the mean

Dispersion value

4.3

C - TVA: MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [C + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD400 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.17

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.83

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

14.159

Variability estimate

Standard error of the mean

Dispersion value

4.22

Primary: Alpha - TVA

Top of page

End point title

Alpha - TVA

End point description

The ratio of reports of targets over distractors

End point type

Primary

End point timeframe

Effects of MPH and ATX on the TVA were tested 90 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the TVA were tested 120 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[101]	32 ^[102]	30 ^[103]	30 ^[104]	30 ^[105]	41 ^[106]	41 ^[107]	43 ^[108]	44 ^[109]	44 ^[110]
Units: ratio
arithmetic mean (standard error)	0.14 ( 0.14 )	0.13 ( 0.12 )	0.13 ( 0.13 )	0.13 ( 0.12 )	0.15 ( 0.14 )	0.11 ( 0.15 )	0.13 ( 0.21 )	0.11 ( 0.20 )	0.13 ( 0.31 )	0.15 ( 0.34 )

Notes
[101] - This was conducted in a cross over design
[102] - This was conducted in a cross over design
[103] - This was conducted in a cross over design
[104] - This was conducted in a cross over design
[105] - This was conducted in a cross over design
[106] - This was conducted in a cross over design
[107] - This was conducted in a cross over design
[108] - This was conducted in a cross over design
[109] - This was conducted in a cross over design
[110] - This was conducted in a cross over design

Alpha - TVA: MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [Alpha + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.87

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.043

upper limit

0.036

Variability estimate

Standard error of the mean

Dispersion value

0.02

Alpha - TVA: MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [Alpha + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.89

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.043

upper limit

0.037

Variability estimate

Standard error of the mean

Dispersion value

0.02

Alpha - TVA: ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [Alpha + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.87

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.043

upper limit

0.037

Variability estimate

Standard error of the mean

Dispersion value

0.02

Alpha - TVA: ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [Alpha + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.81

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.036

upper limit

0.045

Variability estimate

Standard error of the mean

Dispersion value

0.02

Alpha - TVA: AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [Alpha + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.53

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0633

upper limit

0.032

Variability estimate

Standard error of the mean

Dispersion value

0.02

Alpha - TVA: AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [Alpha + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - AMPH20 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.15

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.082

upper limit

0.013

Variability estimate

Standard error of the mean

Dispersion value

0.02

Alpha - TVA: MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [Alpha + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD200 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.035

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.097

upper limit

-0.003

Variability estimate

Standard error of the mean

Dispersion value

0.02

Alpha - TVA: MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [Alpha + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - MOD400 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.31

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.069

upper limit

0.022

Variability estimate

Standard error of the mean

Dispersion value

0.02

Secondary: w-index - TVA

Top of page

End point title

w-index - TVA

End point description

The w-index of the TVA provides the ratio between targets reported in the left or right visual hemisphere

End point type

Secondary

End point timeframe

Effects of MPH and ATX on the TVA were tested 90 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the TVA were tested 120 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[111]	32 ^[112]	30 ^[113]	30 ^[114]	30 ^[115]	41 ^[116]	41 ^[117]	43 ^[118]	44 ^[119]	44 ^[120]
Units: ratio
arithmetic mean (standard error)	0.512 ( 0.021 )	0.519 ( 0.022 )	0.0495 ( 0.019 )	0.514 ( 0.019 )	0.529 ( 0.021 )	0.496 ( 0.019 )	0.494 ( 0.018 )	0.503 ( 0.019 )	0.499 ( 0.015 )	0.500 ( 0.017 )

Notes
[111] - The study was conducted in a cross over design
[112] - The study was conducted in a cross over design
[113] - The study was conducted in a cross over design
[114] - The study was conducted in a cross over design
[115] - The study was conducted in a cross over design
[116] - The study was conducted in a cross over design
[117] - The study was conducted in a cross over design
[118] - The study was conducted in a cross over design
[119] - The study was conducted in a cross over design
[120] - The study was conducted in a cross over design

w-index - TVA: MPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [w-index + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.56

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.016

upper limit

0.029

Variability estimate

Standard error of the mean

Dispersion value

0.01

w-index - TVA: MPH40

Statistical analysis description

Evaluated via a linear mixed-effects model: [w-index + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.26

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.037

upper limit

0.009

Variability estimate

Standard error of the mean

Dispersion value

0.01

w-index - TVA: ATX40

Statistical analysis description

Evaluated via a linear mixed-effects model: [w-index + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.78

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.02

upper limit

0.027

Variability estimate

Standard error of the mean

Dispersion value

0.01

w-index - TVA: ATX60

Statistical analysis description

Evaluated via a linear mixed-effects model: [w-index + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.08

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.003

upper limit

0.045

Variability estimate

Standard error of the mean

Dispersion value

0.01

w-index - TVA: AMPH10

Statistical analysis description

Evaluated via a linear mixed-effects model: [w-index + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.64

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.005

Confidence interval

level

95%

sides

2-sided

lower limit

-0.025

upper limit

0.015

Variability estimate

Standard error of the mean

Dispersion value

0.01

w-index - TVA: AMPH20

Statistical analysis description

Evaluated via a linear mixed-effects model: [w-index + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.61

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.026

upper limit

0.015

Variability estimate

Standard error of the mean

Dispersion value

0.01

w-index - TVA: MOD200

Statistical analysis description

Evaluated via a linear mixed-effects model: [w-index + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.85

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.002

Confidence interval

level

95%

sides

2-sided

lower limit

-0.018

upper limit

0.022

Variability estimate

Standard error of the mean

Dispersion value

0.01

w-index - TVA: MOD400

Statistical analysis description

Evaluated via a linear mixed-effects model: [w-index + Visit + Sex + Baseline + Drug + (1 I SubjectId]

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.46

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.027

upper limit

0.012

Variability estimate

Standard error of the mean

Dispersion value

0.01

Secondary: VAS-A0 - Alertness

Top of page

End point title

VAS-A0 - Alertness

End point description

Visual Analogue Scale - Alertness version

End point type

Secondary

End point timeframe

Administered at the time of drug intake

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[121]	32 ^[122]	30 ^[123]	30 ^[124]	30 ^[125]	41 ^[126]	41 ^[127]	43 ^[128]	44 ^[129]	44 ^[130]
Units: percentage points
arithmetic mean (standard deviation)	53.76 ( 16.2 )	57.07 ( 15.1 )	50.52 ( 17.2 )	54.10 ( 17.5 )	51.76 ( 17.8 )	46.43 ( 15.9 )	47.92 ( 19.3 )	48.35 ( 18.3 )	49.73 ( 19.3 )	47.0 ( 21.2 )

Notes
[121] - Conducted in a cross over design
[122] - Conducted in a cross over design
[123] - Conducted in a cross over design
[124] - Conducted in a cross over design
[125] - Conducted in a cross over design
[126] - Conducted in a cross over design
[127] - Conducted in a cross over design
[128] - Conducted in a cross over design
[129] - Conducted in a cross over design
[130] - Conducted in a cross over design

VAS-A0: MPH20

Statistical analysis description

Repeated Measures Anova

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.92

Method

ANOVA

Parameter type

Mean difference (final values)

Confidence interval

VAS-A0: MPH40

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.12

Method

ANOVA

Confidence interval

VAS-A0: ATX40

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.53

Method

ANOVA

Confidence interval

VAS-A0: ATX60

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.23

Method

ANOVA

Confidence interval

VAS-A0: AMPH10

Comparison groups

Part B - AMPH10 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.89

Method

ANOVA

Confidence interval

VAS-A0: AMPH20

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.79

Method

ANOVA

Confidence interval

VAS-A0: MOD200

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.69

Method

ANOVA

Confidence interval

VAS-A0: MOD400

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.44

Method

ANOVA

Confidence interval

Secondary: VAS-A1 - Alertness

Top of page

End point title

VAS-A1 - Alertness

End point description

End point type

Secondary

End point timeframe

Effects of MPH and ATX on the VAS-A1 were tested 90 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the VAS-A1 were tested 120 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[131]	32 ^[132]	30 ^[133]	30 ^[134]	30 ^[135]	41 ^[136]	41 ^[137]	43 ^[138]	44 ^[139]	44 ^[140]
Units: percentage points
arithmetic mean (standard deviation)	49.48 ( 18.6 )	64.79 ( 24.3 )	73.45 ( 20.6 )	49.69 ( 22.7 )	36.17 ( 19.9 )	64.30 ( 22.0 )	77.14 ( 22.9 )	56.22 ( 20.2 )	67.76 ( 17.6 )	48.47 ( 22.7 )

Notes
[131] - This was conducted in a cross over design
[132] - This was conducted in a cross over design
[133] - This was conducted in a cross over design
[134] - This was conducted in a cross over design
[135] - This was conducted in a cross over design
[136] - This was conducted in a cross over design
[137] - This was conducted in a cross over design
[138] - This was conducted in a cross over design
[139] - This was conducted in a cross over design
[140] - This was conducted in a cross over design

VAS-A1: MPH20

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.004

Method

ANOVA

Confidence interval

VAS-A1: MPH40

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

VAS-A1: ATX40

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.97

Method

ANOVA

Confidence interval

VAS-A1: ATX60

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.015

Method

ANOVA

Confidence interval

VAS-A1: AMPH10

Comparison groups

Part B - AMPH10 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.002

Method

ANOVA

Confidence interval

VAS-A1: AMPH20

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

VAS-A1: MOD200

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.12

Method

ANOVA

Confidence interval

VAS-A1: MOD400

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.001

Method

ANOVA

Confidence interval

Secondary: VAS-A2 - Alertness

Top of page

End point title

VAS-A2 - Alertness

End point description

End point type

Secondary

End point timeframe

Effects of MPH and ATX on the VAS-A2 were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the VAS-A2 were tested 145 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[141]	32 ^[142]	30 ^[143]	30 ^[144]	30 ^[145]	41 ^[146]	41 ^[147]	43 ^[148]	44 ^[149]	44 ^[150]
Units: Percentage Points
arithmetic mean (standard deviation)	37.28 ( 23.2 )	66.14 ( 19.0 )	76.07 ( 18.9 )	37.10 ( 26.24 )	31.14 ( 20.7 )	62.16 ( 21.9 )	73.46 ( 21.3 )	51.19 ( 22.6 )	60.24 ( 16.3 )	33.32 ( 22.8 )

Notes
[141] - This was performed in a cross over design
[142] - This was performed in a cross over design
[143] - This was performed in a cross over design
[144] - This was performed in a cross over design
[145] - This was performed in a cross over design
[146] - This was performed in a cross over design
[147] - This was performed in a cross over design
[148] - This was performed in a cross over design
[149] - This was performed in a cross over design
[150] - This was performed in a cross over design

No statistical analyses for this end point

Secondary: VAS-P - Pleasurability

Top of page

End point title

VAS-P - Pleasurability

End point description

Visual Analogue Scale - Pleasurability: "How pleasureable was the cognitive test session?"

End point type

Secondary

End point timeframe

Effects of MPH and ATX on the VAS-P were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the VAS-P were tested 145 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[151]	32 ^[152]	30 ^[153]	30 ^[154]	30 ^[155]	41 ^[156]	41 ^[157]	43 ^[158]	44 ^[159]	44 ^[160]
Units: Percentage Points
arithmetic mean (standard deviation)	34.21 ( 20.8 )	59.34 ( 23.3 )	65.17 ( 25.0 )	33.62 ( 23.9 )	31.21 ( 20.6 )	48.7 ( 24.8 )	55.9 ( 30.5 )	39.2 ( 24.9 )	47.5 ( 22.8 )	26.6 ( 22.3 )

Notes
[151] - Conducted in a cross over design
[152] - Conducted in a cross over design
[153] - Conducted in a cross over design
[154] - Conducted in a cross over design
[155] - Conducted in a cross over design
[156] - Conducted in a cross over design
[157] - Conducted in a cross over design
[158] - Conducted in a cross over design
[159] - Conducted in a cross over design
[160] - Conducted in a cross over design

VAS-P: MPH20

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

VAS-P: MPH40

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

VAS-P: ATX40

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.88

Method

ANOVA

Confidence interval

VAS-P: ATX60

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.46

Method

ANOVA

Confidence interval

VAS-P: AMPH10

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

VAS-P: AMPH20

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

VAS-P: MOD200

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

VAS-P: MOD400

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

Secondary: HR - CPT - Heart Rate

Top of page

End point title

HR - CPT - Heart Rate

End point description

End point type

Secondary

End point timeframe

Heart Rate while performing the CPT test. Effects of MPH and ATX on the CPT were tested 125 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[161]	32 ^[162]	30 ^[163]	30 ^[164]	30 ^[165]	41 ^[166]	41 ^[167]	43 ^[168]	44 ^[169]	44 ^[170]
Units: Beats pr minute
arithmetic mean (standard deviation)	69 ( 8.47 )	79 ( 13.38 )	82 ( 15.92 )	77 ( 12.56 )	76 ( 13.66 )	81 ( 13.27 )	84 ( 13.90 )	80 ( 13.93 )	84 ( 12.28 )	71 ( 11.14 )

Notes
[161] - Conducted in a cross over design
[162] - Conducted in a cross over design
[163] - Conducted in a cross over design
[164] - Conducted in a cross over design
[165] - Conducted in a cross over design
[166] - Conducted in a cross over design
[167] - Conducted in a cross over design
[168] - Conducted in a cross over design
[169] - Conducted in a cross over design
[170] - Conducted in a cross over design

HR - CPT: MPH20

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - CPT: MPH40

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - CPT: ATX40

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - CPT: ATX60

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.001

Method

ANOVA

Confidence interval

HR - CPT: AMPH10

Comparison groups

Part B - Placebo v Part B - AMPH10

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - CPT: AMPH20

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - CPT: MOD200

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - CPT: MOD400

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

Secondary: HRV-CPT - RMSSQ

Top of page

End point title

HRV-CPT - RMSSQ

End point description

End point type

Secondary

End point timeframe

Heart Rate Variability - The root mean square of the standard deviation during the CPT test. Effects of MPH and ATX on the CPT were tested 125 minutes after drug or placebo. Effects of AMPH and MOD on the CPT were tested 155 minutes after drug or placeb

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[171]	32 ^[172]	30 ^[173]	30 ^[174]	30 ^[175]	41 ^[176]	41 ^[177]	43 ^[178]	44 ^[179]	44 ^[180]
Units: beats pr minute
arithmetic mean (standard deviation)	53 ( 23.01 )	41 ( 17.94 )	40 ( 21.63 )	38 ( 15.66 )	41 ( 20.19 )	40 ( 24.73 )	36 ( 18.01 )	42 ( 24.68 )	37 ( 18.78 )	51 ( 22.41 )

Notes
[171] - Conducted in a cross over design
[172] - Conducted in a cross over design
[173] - Conducted in a cross over design
[174] - Conducted in a cross over design
[175] - Conducted in a cross over design
[176] - Conducted in a cross over design
[177] - Conducted in a cross over design
[178] - Conducted in a cross over design
[179] - Conducted in a cross over design
[180] - Conducted in a cross over design

HRV-CPT: MPH20

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.002

Method

ANOVA

Confidence interval

HRV-CPT: MPH40

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.004

Method

ANOVA

Confidence interval

HRV-CPT: ATX40

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HRV-CPT: ATX60

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.008

Method

ANOVA

Confidence interval

HRV-CPT: AMPH10

Comparison groups

Part B - AMPH10 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.009

Method

ANOVA

Confidence interval

HRV-CPT: AMPH20

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HRV-CPT: MOD200

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.016

Method

ANOVA

Confidence interval

HRV-CPT: MOD400

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

Secondary: HR - TVA - Heart Rate

Top of page

End point title

HR - TVA - Heart Rate

End point description

Heart Rate during the TVA test

End point type

Secondary

End point timeframe

Data was collected during the TVA test Effects of MPH and ATX on the TVA were tested 90 minutes after ingestion of drug or placebo. Effects of AMPH and MOD on the TVA were tested 120 minutes after ingestion of drug or placebo.

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[181]	32 ^[182]	30 ^[183]	30 ^[184]	30 ^[185]	41 ^[186]	41 ^[187]	43 ^[188]	44 ^[189]	44 ^[190]
Units: beats pr minute
arithmetic mean (standard deviation)	73 ( 9.23 )	82 ( 11.51 )	85 ( 15.82 )	81 ( 14.17 )	81 ( 15.11 )	86 ( 13.83 )	86 ( 13.87 )	85 ( 12.73 )	89 ( 14.55 )	75 ( 12.29 )

Notes
[181] - This was conducted in a cross over design
[182] - This was conducted in a cross over design
[183] - This was conducted in a cross over design
[184] - This was conducted in a cross over design
[185] - This was conducted in a cross over design
[186] - This was conducted in a cross over design
[187] - This was conducted in a cross over design
[188] - This was conducted in a cross over design
[189] - This was conducted in a cross over design
[190] - This was conducted in a cross over design

HR - TVA: MPH20

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - TVA: MPH40

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - TVA: ATX40

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - TVA: ATX60

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.002

Method

ANOVA

Confidence interval

HR - TVA: AMPH10

Comparison groups

Part B - AMPH10 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - TVA: AMPH20

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - TVA: MOD200

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

HR - TVA: MOD400

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

Secondary: HRV - TVA - RMSSQ

Top of page

End point title

HRV - TVA - RMSSQ

End point description

End point type

Secondary

End point timeframe

The root mean square of the standard deviation of heart rate during the TVA test. Effects of MPH and ATX on the TVA were tested 90 minutes after drug or placebo. Effects of AMPH and MOD on the TVA were tested 120 minutes after drug or placebo

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	32 ^[191]	32 ^[192]	30 ^[193]	30 ^[194]	30 ^[195]	41 ^[196]	41 ^[197]	43 ^[198]	44 ^[199]	44 ^[200]
Units: beats pr minute
arithmetic mean (standard deviation)	40 ( 19.67 )	32 ( 14.47 )	30 ( 18.44 )	33 ( 17.43 )	32 ( 18.21 )	30 ( 18.53 )	33 ( 18.76 )	32 ( 15.68 )	29 ( 17.14 )	41 ( 21.92 )

Notes
[191] - Conducted in a cross over design
[192] - Conducted in a cross over design
[193] - Conducted in a cross over design
[194] - Conducted in a cross over design
[195] - Conducted in a cross over design
[196] - Conducted in a cross over design
[197] - Conducted in a cross over design
[198] - Conducted in a cross over design
[199] - Conducted in a cross over design
[200] - Conducted in a cross over design

HRV - TVA: MPH20

Comparison groups

Part A - Placebo v Part A - MPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.02

Method

ANOVA

Confidence interval

HRV - TVA: MPH40

Comparison groups

Part A - Placebo v Part A - MPH40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.008

Method

ANOVA

Confidence interval

HRV - TVA: ATX40

Comparison groups

Part A - Placebo v Part A - ATX40

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.65

Method

ANOVA

Confidence interval

HRV - TVA: ATX60

Comparison groups

Part A - Placebo v Part A - ATX60

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.14

Method

ANOVA

Confidence interval

HRV - TVA: AMPH10

Comparison groups

Part B - AMPH10 v Part B - Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.009

Method

ANOVA

Confidence interval

HRV - TVA: AMPH20

Comparison groups

Part B - Placebo v Part B - AMPH20

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.009

Method

ANOVA

Confidence interval

HRV - TVA: MOD200

Comparison groups

Part B - Placebo v Part B - MOD200

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.004

Method

ANOVA

Confidence interval

Copy of HRV - TVA: MOD400

Comparison groups

Part B - Placebo v Part B - MOD400

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

< 0.001

Method

ANOVA

Confidence interval

Post-hoc: MPH plasma concentration (mg /kg)

Top of page

End point title

MPH plasma concentration (mg /kg)

End point description

End point type

Post-hoc

End point timeframe

Blood samples were drawn upon completion of each test session

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60
Number of subjects analysed	35	35	35	35	35
Units: mg / kg
number (not applicable)	0.0	0.001	0.018	0.0	0.0

No statistical analyses for this end point

Post-hoc: MPH plasma concentration (ng / L)

Top of page

End point title

MPH plasma concentration (ng / L)

End point description

End point type

Post-hoc

End point timeframe

Blood samples were drawn upon completion of each test session

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60
Number of subjects analysed	35	35	35	35	35
Units: ng / L
number (not applicable)	0.0	9.238	17.692	0.0	0.0

No statistical analyses for this end point

Post-hoc: ATX plasma concentration (mg / kg)

Top of page

End point title

ATX plasma concentration (mg / kg)

End point description

End point type

Post-hoc

End point timeframe

Blood samples were drawn upon completion of each test session

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60
Number of subjects analysed	35	35	35	35	35
Units: mg / kg
number (not applicable)	0.0	0.0	0.0	0.253	0.364

No statistical analyses for this end point

Post-hoc: ATX plasma concentration (ng / L)

Top of page

End point title

ATX plasma concentration (ng / L)

End point description

End point type

Post-hoc

End point timeframe

Blood samples were drawn upon completion of each test session

End point values	Part A - Placebo	Part A - MPH20	Part A - MPH40	Part A - ATX40	Part A - ATX60
Number of subjects analysed	35	35	35	35	35
Units: ng / L
number (not applicable)	0.0	0.0	0.0	248.5	356.8

No statistical analyses for this end point

Post-hoc: AMPH plasma concentration (mg / kg)

Top of page

End point title

AMPH plasma concentration (mg / kg)

End point description

End point type

Post-hoc

End point timeframe

Blood samples were drawn upon the completion of each test session

End point values	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	48	48	48	48	48
Units: mg / kg
number (not applicable)	0.024	0.049	0.0	0.0	0.0

No statistical analyses for this end point

Post-hoc: MOD plasma concentration (mg / kg)

Top of page

End point title

MOD plasma concentration (mg / kg)

End point description

End point type

Post-hoc

End point timeframe

Blood samples were drawn upon the completion of each test session

End point values	Part B - AMPH10	Part B - AMPH20	Part B - MOD200	Part B - MOD400	Part B - Placebo
Number of subjects analysed	48	48	48	48	48
Units: mg / kg
number (not applicable)	0.0	0.0	3.5	7.8	0.0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Upon completion of each test session a questionnaire was provided for each participant to fill out.

Assessment type

Systematic

Dictionary name

none

Dictionary version

Reporting group title

AIM-C Part A - Placebo

Reporting group description

Reporting group title

AIM-C Part B - Placebo

Reporting group description

Reporting group title

AIM-C Part A - MPH20

Reporting group description

Reporting group title

AIM-C Part A - MPH40

Reporting group description

Reporting group title

AIM-C Part A - ATX40

Reporting group description

Reporting group title

AIM-C Part A - ATX60

Reporting group description

Reporting group title

AIM-C Part B - AMPH10

Reporting group description

Reporting group title

AIM-C Part B - AMPH20

Reporting group description

Reporting group title

AIM-C Part B - MOD200

Reporting group description

Reporting group title

AIM-C Part B - MOD400

Reporting group description

Serious adverse events	AIM-C Part A - Placebo	AIM-C Part B - Placebo	AIM-C Part A - MPH20	AIM-C Part A - MPH40	AIM-C Part A - ATX40	AIM-C Part A - ATX60	AIM-C Part B - AMPH10	AIM-C Part B - AMPH20	AIM-C Part B - MOD200	AIM-C Part B - MOD400
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 32 (0.00%)	0 / 44 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)	0 / 43 (0.00%)	0 / 44 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	AIM-C Part A - Placebo	AIM-C Part B - Placebo	AIM-C Part A - MPH20	AIM-C Part A - MPH40	AIM-C Part A - ATX40	AIM-C Part A - ATX60	AIM-C Part B - AMPH10	AIM-C Part B - AMPH20	AIM-C Part B - MOD200	AIM-C Part B - MOD400
Total subjects affected by non serious adverse events
subjects affected / exposed	14 / 32 (43.75%)	17 / 44 (38.64%)	12 / 32 (37.50%)	11 / 30 (36.67%)	19 / 30 (63.33%)	24 / 30 (80.00%)	22 / 41 (53.66%)	15 / 41 (36.59%)	11 / 43 (25.58%)	16 / 44 (36.36%)
General disorders and administration site conditions
Sleepy / tired
subjects affected / exposed	14 / 32 (43.75%)	16 / 44 (36.36%)	5 / 32 (15.63%)	3 / 30 (10.00%)	14 / 30 (46.67%)	15 / 30 (50.00%)	6 / 41 (14.63%)	0 / 41 (0.00%)	3 / 43 (6.98%)	2 / 44 (4.55%)
occurrences all number	14	16	5	3	14	15	6	0	3	2
dizzy
subjects affected / exposed	1 / 32 (3.13%)	0 / 44 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	1 / 30 (3.33%)	2 / 30 (6.67%)	3 / 41 (7.32%)	7 / 41 (17.07%)	2 / 43 (4.65%)	3 / 44 (6.82%)
occurrences all number	1	0	0	0	1	2	3	7	2	3
perceived increased heart rate
subjects affected / exposed	0 / 32 (0.00%)	1 / 44 (2.27%)	5 / 32 (15.63%)	3 / 30 (10.00%)	1 / 30 (3.33%)	3 / 30 (10.00%)	5 / 41 (12.20%)	6 / 41 (14.63%)	1 / 43 (2.33%)	4 / 44 (9.09%)
occurrences all number	0	1	5	3	1	3	5	6	1	4
feeling unfocused
subjects affected / exposed	2 / 32 (6.25%)	0 / 44 (0.00%)	1 / 32 (3.13%)	0 / 30 (0.00%)	0 / 30 (0.00%)	5 / 30 (16.67%)	2 / 41 (4.88%)	1 / 41 (2.44%)	0 / 43 (0.00%)	1 / 44 (2.27%)
occurrences all number	2	0	1	0	0	5	2	1	0	1
feeling restless
subjects affected / exposed	0 / 32 (0.00%)	0 / 44 (0.00%)	0 / 32 (0.00%)	5 / 30 (16.67%)	0 / 30 (0.00%)	0 / 30 (0.00%)	3 / 41 (7.32%)	1 / 41 (2.44%)	1 / 43 (2.33%)	4 / 44 (9.09%)
occurrences all number	0	0	0	5	0	0	3	1	1	4
feeling jittery / tingly
subjects affected / exposed	0 / 32 (0.00%)	0 / 44 (0.00%)	2 / 32 (6.25%)	2 / 30 (6.67%)	1 / 30 (3.33%)	0 / 30 (0.00%)	6 / 41 (14.63%)	0 / 41 (0.00%)	2 / 43 (4.65%)	2 / 44 (4.55%)
occurrences all number	0	0	2	2	1	0	6	0	2	2
feeling nauseous
subjects affected / exposed	0 / 32 (0.00%)	2 / 44 (4.55%)	1 / 32 (3.13%)	1 / 30 (3.33%)	5 / 30 (16.67%)	7 / 30 (23.33%)	0 / 41 (0.00%)	0 / 41 (0.00%)	2 / 43 (4.65%)	0 / 44 (0.00%)
occurrences all number	0	2	1	1	5	7	0	0	2	0

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: STUDY OF ATTENTION AND IMPULSIVITY IN HEALTHY HUMAN VOLUNTEERS

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: d-prime CPT

Primary: d-prime CPT

Primary: C - CPT

Primary: C - CPT

Primary: HRT - CPT

Primary: HRT - CPT

Primary: HRT.SD - CPT

Primary: HRT.SD - CPT

Primary: VAR - CPT

Primary: VAR - CPT

Primary: BLKCH - CPT

Primary: BLKCH - CPT

Primary: ISI - CPT

Primary: ISI - CPT

Primary: K - TVA

Primary: K - TVA

Primary: t0 - TVA

Primary: t0 - TVA

Primary: C - TVA

Primary: C - TVA

Primary: Alpha - TVA

Primary: Alpha - TVA

Secondary: w-index - TVA

Secondary: w-index - TVA

Secondary: VAS-A0 - Alertness

Secondary: VAS-A0 - Alertness

Secondary: VAS-A1 - Alertness

Secondary: VAS-A1 - Alertness

Secondary: VAS-A2 - Alertness

Secondary: VAS-A2 - Alertness

Secondary: VAS-P - Pleasurability

Secondary: VAS-P - Pleasurability

Secondary: HR - CPT - Heart Rate

Secondary: HR - CPT - Heart Rate

Secondary: HRV-CPT - RMSSQ

Secondary: HRV-CPT - RMSSQ

Secondary: HR - TVA - Heart Rate

Secondary: HR - TVA - Heart Rate

Secondary: HRV - TVA - RMSSQ

Secondary: HRV - TVA - RMSSQ

Post-hoc: MPH plasma concentration (mg /kg)

Post-hoc: MPH plasma concentration (mg /kg)

Post-hoc: MPH plasma concentration (ng / L)

Post-hoc: MPH plasma concentration (ng / L)

Post-hoc: ATX plasma concentration (mg / kg)

Post-hoc: ATX plasma concentration (mg / kg)

Post-hoc: ATX plasma concentration (ng / L)

Post-hoc: ATX plasma concentration (ng / L)

Post-hoc: AMPH plasma concentration (mg / kg)

Post-hoc: AMPH plasma concentration (mg / kg)

Post-hoc: MOD plasma concentration (mg / kg)

Post-hoc: MOD plasma concentration (mg / kg)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
STUDY OF ATTENTION AND IMPULSIVITY IN HEALTHY HUMAN VOLUNTEERS