Trial Outcomes & Findings for Open Label, Multicentre Extension Study of Protocol 42603ATT3002 to Evaluate Safety of Prolonged Release OROS Methlyphenidate in Adults With Attention Deficit Hyperactivity Disorder (ADHD) (NCT NCT00307684)
NCT ID: NCT00307684
Last Updated: 2014-04-21
Results Overview
To evaluate the long term safety and tolerability of PR OROS MPH (18, 36, 54, 72 and 90 mg/day) in adults with Attention Deficit Hyperactivity Disorder (ADHD)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
155 participants
Primary outcome timeframe
Treatment duration for OL extended from 52 wks to 72 wks (International Amendment 2) or 108 wks in Germany. Treatment duration for double-blind (DB) randomized withdrawal: 4 weeks
Results posted on
2014-04-21
Participant Flow
Subjects were recruited by Psychiatrists both at medical clinics and private practices between 13-Jan-2006 and 14-Nov-2006
Subjects who participated in the 42603ATT3002 study and still met all eligibility criteria could enter open-label (OL) phase of this study. Subjects who had received at least 52 weeks of uninterrupted treatment with PR OROS methylphenidate (MPH) and provided informed consent could enter the double-blind phase (DB).45 subjects consented for DB.
Participant milestones
| Measure |
Active
PR OROS MPH 18 to 90 mg once daily
|
Placebo
matching placebo
|
Open Label PR OROS MPH
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Open Label Phase
STARTED
|
0
|
0
|
155
|
|
Open Label Phase
COMPLETED
|
0
|
0
|
99
|
|
Open Label Phase
NOT COMPLETED
|
0
|
0
|
56
|
|
Double Blind Phase
STARTED
|
23
|
22
|
0
|
|
Double Blind Phase
COMPLETED
|
21
|
17
|
0
|
|
Double Blind Phase
NOT COMPLETED
|
2
|
5
|
0
|
Reasons for withdrawal
| Measure |
Active
PR OROS MPH 18 to 90 mg once daily
|
Placebo
matching placebo
|
Open Label PR OROS MPH
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Open Label Phase
Lack of Efficacy
|
0
|
0
|
3
|
|
Open Label Phase
Adverse Event
|
0
|
0
|
16
|
|
Open Label Phase
Withdrawal by Subject
|
0
|
0
|
15
|
|
Open Label Phase
Lost to Follow-up
|
0
|
0
|
11
|
|
Open Label Phase
non compliance
|
0
|
0
|
5
|
|
Open Label Phase
other
|
0
|
0
|
6
|
|
Double Blind Phase
Lack of Efficacy
|
2
|
5
|
0
|
Baseline Characteristics
Open Label, Multicentre Extension Study of Protocol 42603ATT3002 to Evaluate Safety of Prolonged Release OROS Methlyphenidate in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Baseline characteristics by cohort
| Measure |
Overall Study Population
n=155 Participants
Prolonged release (PR) Osmotic Release Oral Systems (OROS) MPH 18 to 90 mg once daily during the OL phase. Subjects who had received at 52 weeks of uninterrupted treatment with PR OROS MPH and provided consent for the DB phase were randomly assigned to placebo or their previous dose of PR OROS MPH (18 to 90 mg once daily)
|
|---|---|
|
Age, Continuous
|
35.0 years
STANDARD_DEVIATION 10.60 • n=99 Participants
|
|
Sex: Female, Male
Female
|
71 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
84 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African heritage
|
1 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Other: Asian white
|
1 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Other: Northern-African + Hindustan
|
1 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
152 participants
n=99 Participants
|
|
Weight
|
75.1 kg
STANDARD_DEVIATION 16.46 • n=99 Participants
|
|
body mass index (BMI)
|
24.8 kg/m2
STANDARD_DEVIATION 4.47 • n=99 Participants
|
PRIMARY outcome
Timeframe: Treatment duration for OL extended from 52 wks to 72 wks (International Amendment 2) or 108 wks in Germany. Treatment duration for double-blind (DB) randomized withdrawal: 4 weeksPopulation: intent-to-treat: all subjects who used the study medication at least once
To evaluate the long term safety and tolerability of PR OROS MPH (18, 36, 54, 72 and 90 mg/day) in adults with Attention Deficit Hyperactivity Disorder (ADHD)
Outcome measures
| Measure |
Active
n=23 Participants
PR OROS MPH 18 to 90 mg once daily
|
Placebo
n=22 Participants
matching placebo
|
Open Label PR OROS MPH
n=155 Participants
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
at least one AE
|
7 participants
|
8 participants
|
126 participants
|
|
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
at least one SAE
|
0 participants
|
1 participants
|
12 participants
|
|
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
at least one severe AE
|
0 participants
|
3 participants
|
27 participants
|
|
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
at least one AE with concomitant therapy
|
0 participants
|
4 participants
|
93 participants
|
|
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
at least one AE leading to permanent stop
|
0 participants
|
0 participants
|
15 participants
|
|
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
at least one AE leading to temporary stop
|
0 participants
|
2 participants
|
23 participants
|
|
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
at least one AE at least possibly related
|
3 participants
|
5 participants
|
62 participants
|
PRIMARY outcome
Timeframe: DB baseline, DB endpointPopulation: intent to treat: all subjects who used trial medication at least once
To evaluate maintenance of treatment effects of PR OROS MPH vs. placebo as measured on CAARS. CAARS assesses ADHD symptoms and behaviors in adults. best value: 0 worst value: 54 Endpoint: last available post-baseline assessment.
Outcome measures
| Measure |
Active
n=23 Participants
PR OROS MPH 18 to 90 mg once daily
|
Placebo
n=22 Participants
matching placebo
|
Open Label PR OROS MPH
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Change From DB Baseline in Conners' Adult ADHD Rating Scale (CAARS) Total Score at DB Endpoint
|
4.0 units on a scale
Standard Deviation 7.61
|
6.5 units on a scale
Standard Deviation 7.82
|
—
|
SECONDARY outcome
Timeframe: OL baseline, OL endpointPopulation: intent to treat: all subjects who used trial medication at least once
Long term efficacy of PR OROS MPH as assessed by investigator-rated CAARS total score, hyperactivity/impulsivity subscale score and inattention subscale score. Subscale scores: best value: 0, worst value: 27
Outcome measures
| Measure |
Active
PR OROS MPH 18 to 90 mg once daily
|
Placebo
matching placebo
|
Open Label PR OROS MPH
n=155 Participants
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Change From OL Baseline to OL Endpoint in Conners' Adult ADHD Rating Scale (CAARS) Total and Subscale Scores
change from baseline to endpoint in total score
|
—
|
—
|
-1.9 units on a scale
Standard Deviation 7.82
|
|
Change From OL Baseline to OL Endpoint in Conners' Adult ADHD Rating Scale (CAARS) Total and Subscale Scores
change from baseline to endpoint in inattention
|
—
|
—
|
-1.0 units on a scale
Standard Deviation 4.63
|
|
Change From OL Baseline to OL Endpoint in Conners' Adult ADHD Rating Scale (CAARS) Total and Subscale Scores
change from baseline to endpoint in hyperactivity
|
—
|
—
|
-0.9 units on a scale
Standard Deviation 4.36
|
SECONDARY outcome
Timeframe: OL baseline, OL endpointPopulation: intent to treat: all subjects who used trial medication at least once
Assessment of the long term effect on overall functioning measured by CGI-S best score: 1 worst score: 7
Outcome measures
| Measure |
Active
PR OROS MPH 18 to 90 mg once daily
|
Placebo
matching placebo
|
Open Label PR OROS MPH
n=155 Participants
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Change From OL Baseline in Clinical Global Impression Scale (CGI-S) Score at OL Endpoint
|
—
|
—
|
-0.3 units on a scale
Standard Deviation 1.10
|
SECONDARY outcome
Timeframe: OL baseline, OL endpointPopulation: intent to treat: all subjects who used trial medication at least once
Quality of life measured by Q-LES-Q best score: 100 worst score: 0
Outcome measures
| Measure |
Active
PR OROS MPH 18 to 90 mg once daily
|
Placebo
matching placebo
|
Open Label PR OROS MPH
n=155 Participants
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Change From OL Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Score at OL Endpoint
|
—
|
—
|
1.4 units on a scale
Standard Deviation 15.15
|
SECONDARY outcome
Timeframe: DB baseline, DB endpointPopulation: Intent to treat: all subjects who used study medication at least once
evaluation of treatment effects as rated by the investigator on the CGI-S scale. CGI-S is used to rate the severity of a subject's illness on a 7- point scale ranging from 1 (not ill) to 7 (extremely severe).
Outcome measures
| Measure |
Active
n=23 Participants
PR OROS MPH 18 to 90 mg once daily
|
Placebo
n=22 Participants
matching placebo
|
Open Label PR OROS MPH
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Change From DB Baseline to DB Endpoint in CGI-S Score
|
0.6 units on a scale
Standard Deviation 1.08
|
1.0 units on a scale
Standard Deviation 1.23
|
—
|
SECONDARY outcome
Timeframe: DB baseline, DB endpointEvaluation of treatment effects as rated by the subjects on the CAARS-S:S. best score: 0 worst score: 104
Outcome measures
| Measure |
Active
n=22 Participants
PR OROS MPH 18 to 90 mg once daily
|
Placebo
n=21 Participants
matching placebo
|
Open Label PR OROS MPH
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Change From DB Baseline to DB Endpoint in CAARS Self Rated Scale (CAARS-S:S) Total Score
|
4.4 units on a scale
Standard Deviation 11.90
|
4.0 units on a scale
Standard Deviation 11.98
|
—
|
Adverse Events
Active
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Open Label PR OROS MPH
Serious events: 12 serious events
Other events: 126 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Active
n=23 participants at risk
PR OROS MPH 18 to 90 mg once daily
|
Placebo
n=22 participants at risk
matching placebo
|
Open Label PR OROS MPH
n=155 participants at risk
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Surgical and medical procedures
Hip arthroplasty
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Surgical and medical procedures
Hip surgery
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Surgical and medical procedures
Lipoma excision
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Surgical and medical procedures
Mastectomy
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Surgical and medical procedures
Tonsillectomy
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer recurrent
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
0.65%
1/155 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Reproductive system and breast disorders
Uterine hemorrhage
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Ear and labyrinth disorders
Deafness
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Immune system disorders
Allergy to arthropod sting
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Injury, poisoning and procedural complications
Whiplash injury
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Investigations
Investigation
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
0.00%
0/23
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Surgical and medical procedures
Breast reconstruction
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
0.00%
0/155
|
Other adverse events
| Measure |
Active
n=23 participants at risk
PR OROS MPH 18 to 90 mg once daily
|
Placebo
n=22 participants at risk
matching placebo
|
Open Label PR OROS MPH
n=155 participants at risk
PR OROS MPH 18 to 90 mg once daily
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
4.3%
1/23 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
20.0%
31/155 • Number of events 44
|
|
Infections and infestations
Influenza
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
6.5%
10/155 • Number of events 12
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/23
|
0.00%
0/22
|
3.9%
6/155 • Number of events 10
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/23
|
0.00%
0/22
|
3.9%
6/155 • Number of events 6
|
|
Infections and infestations
Sinusitis
|
0.00%
0/23
|
0.00%
0/22
|
3.2%
5/155 • Number of events 5
|
|
Infections and infestations
Bronchitis
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 4
|
|
Psychiatric disorders
Restlessness
|
4.3%
1/23 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
7.7%
12/155 • Number of events 14
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/23
|
0.00%
0/22
|
7.1%
11/155 • Number of events 13
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
5.2%
8/155 • Number of events 8
|
|
Psychiatric disorders
Initial insomnia
|
0.00%
0/23
|
0.00%
0/22
|
4.5%
7/155 • Number of events 9
|
|
Psychiatric disorders
Nervousness
|
0.00%
0/23
|
0.00%
0/22
|
3.2%
5/155 • Number of events 7
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 6
|
|
Nervous system disorders
Headache
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
21.3%
33/155 • Number of events 54
|
|
Nervous system disorders
Dizziness
|
4.3%
1/23 • Number of events 2
|
0.00%
0/22
|
4.5%
7/155 • Number of events 8
|
|
Nervous system disorders
Tremor
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/23
|
0.00%
0/22
|
4.5%
7/155 • Number of events 9
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/23
|
0.00%
0/22
|
3.9%
6/155 • Number of events 6
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
3.2%
5/155 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/23
|
0.00%
0/22
|
7.1%
11/155 • Number of events 14
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/23
|
0.00%
0/22
|
3.9%
6/155 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Myosclerosis
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 6
|
|
General disorders
Drug effect decreased
|
0.00%
0/23
|
0.00%
0/22
|
5.8%
9/155 • Number of events 9
|
|
General disorders
Fatigue
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
4.5%
7/155 • Number of events 8
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/23
|
0.00%
0/22
|
3.2%
5/155 • Number of events 5
|
|
Investigations
Blood creatinine increased
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 4
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 5
|
|
Investigations
Neutrophil count increased
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 5
|
|
Investigations
Weight decreased
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 4
|
|
Investigations
Weight increased
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
2.6%
4/155 • Number of events 5
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.00%
0/23
|
0.00%
0/22
|
3.2%
5/155 • Number of events 6
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 4
|
|
Cardiac disorders
Palpitations
|
0.00%
0/23
|
0.00%
0/22
|
3.9%
6/155 • Number of events 6
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/23
|
0.00%
0/22
|
2.6%
4/155 • Number of events 4
|
|
Vascular disorders
Hypertension
|
8.7%
2/23 • Number of events 2
|
0.00%
0/22
|
5.8%
9/155 • Number of events 9
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/23
|
0.00%
0/22
|
3.9%
6/155 • Number of events 6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/23
|
0.00%
0/22
|
4.5%
7/155 • Number of events 8
|
|
Psychiatric disorders
Impatience
|
4.3%
1/23 • Number of events 1
|
0.00%
0/22
|
0.65%
1/155 • Number of events 1
|
|
Psychiatric disorders
Impulsive behavior
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
0.00%
0/155
|
|
Psychiatric disorders
Listless
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
0.00%
0/155
|
|
Psychiatric disorders
Mood swings
|
4.3%
1/23 • Number of events 2
|
0.00%
0/22
|
1.9%
3/155 • Number of events 4
|
|
Psychiatric disorders
Stereotypy
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
0.00%
0/155
|
|
General disorders
Irritability
|
4.3%
1/23 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
1.9%
3/155 • Number of events 4
|
|
General disorders
Pyrexia
|
4.3%
1/23 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
0.65%
1/155 • Number of events 1
|
|
Nervous system disorders
Somnolence
|
4.3%
1/23 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
0.65%
1/155 • Number of events 1
|
|
Vascular disorders
Hematoma
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
0.00%
0/155
|
|
Investigations
Reticulocyte count increased
|
4.3%
1/23 • Number of events 1
|
0.00%
0/22
|
0.00%
0/155
|
|
Eye disorders
Eyelid edema
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
0.00%
0/155
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
4.3%
1/23 • Number of events 1
|
0.00%
0/22
|
0.00%
0/155
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
4.3%
1/23 • Number of events 1
|
0.00%
0/22
|
1.3%
2/155 • Number of events 2
|
|
Surgical and medical procedures
Breast reconstruction
|
0.00%
0/23
|
4.5%
1/22 • Number of events 1
|
0.00%
0/155
|
Additional Information
European Medical Affairs Director Neurology
Janssen-Cilag G.m.b.H.
Phone: +49 2137 955258
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60