Trial Outcomes & Findings for A Study to Evaluate Effectiveness and Safety of Prolonged Release OROS Methylphenidate in Adults With Attention Deficit Hyperactivity Disorder (NCT NCT00714688)

Last Updated: 2014-05-08

Results Overview

The primary endpoint was the change in the ADHD symptoms total score of the investigator-rated CAARS from baseline to the last assessment in the double-blind treatment period. CAARS assesses ADHD symptoms and behaviors in adults using a scale ranging from 0 (best) to 54 (worst). For subjects without a post-baseline efficacy measurement, a change of 0 units was imputed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

279 participants

Primary outcome timeframe

from baseline to 13 weeks

Results posted on

2014-05-08

Participant Flow

This study was conducted from 4 February 2008 (first subject in) to 2 April 2009 (last subject out).

After enrolment patients entered a screening period of up to 2 weeks included the tapering and discontinuation of current forbidden treatment (except if fluoxetine or Monoamine Oxidase (MAO) inhibitors needed to be tapered, in which case a screening period of 4 weeks was allowed).

Participant milestones

Participant milestones
Measure	Placebo 2 tablets placebo once daily for 13 weeks	54 mg PR OROS MPH Prolonged-release (PR) OROS methylphenidate 18 + 36 mg once daily for 13 weeks	72 mg PR OROS MPH Prolonged-release (PR) OROS methylphenidate 2 tablets 36 mg once daily for 13 weeks
Overall Study STARTED	97	90	92
Overall Study COMPLETED	68	55	55
Overall Study NOT COMPLETED	29	35	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 2 tablets placebo once daily for 13 weeks	54 mg PR OROS MPH Prolonged-release (PR) OROS methylphenidate 18 + 36 mg once daily for 13 weeks	72 mg PR OROS MPH Prolonged-release (PR) OROS methylphenidate 2 tablets 36 mg once daily for 13 weeks
Overall Study Lack of Efficacy	14	1	4
Overall Study Withdrawal by Subject	4	3	3
Overall Study Lost to Follow-up	5	2	0
Overall Study Adverse Event	2	15	19
Overall Study Subject Non-compliant	3	5	5
Overall Study Ineligible to Continue the Study	0	1	1
Overall Study Sponsor's Decision	0	2	0
Overall Study Other	1	6	5

Baseline Characteristics

A Study to Evaluate Effectiveness and Safety of Prolonged Release OROS Methylphenidate in Adults With Attention Deficit Hyperactivity Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=97 Participants 2 tablets placebo once daily for 13 weeks	54 mg PR OROS MPH n=90 Participants Prolonged-release (PR) OROS methylphenidate 18 + 36 mg once daily for 13 weeks	72 mg PR OROS MPH n=92 Participants Prolonged-release (PR) OROS methylphenidate 2 tablets 36 mg once daily for 13 weeks	Total n=279 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	96 Participants n=5 Participants	89 Participants n=7 Participants	90 Participants n=5 Participants	275 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	35.5 years STANDARD_DEVIATION 8.81 • n=5 Participants	35.8 years STANDARD_DEVIATION 11.71 • n=7 Participants	35.8 years STANDARD_DEVIATION 10.08 • n=5 Participants	35.7 years STANDARD_DEVIATION 10.20 • n=4 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	46 Participants n=7 Participants	42 Participants n=5 Participants	133 Participants n=4 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	44 Participants n=7 Participants	50 Participants n=5 Participants	146 Participants n=4 Participants

PRIMARY outcome

Timeframe: from baseline to 13 weeks

Population: The ITT analysis set (includes all randomized subjects) was considered the primary efficacy analysis set.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants 2 tablets placebo once daily for 13 weeks	54 mg PR OROS MPH n=90 Participants Prolonged-release (PR) OROS methylphenidate 18 + 36 mg once daily for 13 weeks	72 mg PR OROS MPH n=92 Participants Prolonged-release (PR) OROS methylphenidate 2 tablets 36 mg once daily for 13 weeks
Attention Deficit/Hyperactivity Disorder (ADHD) Symptoms Total Score of the Conners Adult ADHD Rating Scale (CAARS) Baseline	36.5 units on a scale Standard Deviation 6.05	35.6 units on a scale Standard Deviation 6.75	37.3 units on a scale Standard Deviation 6.35
Attention Deficit/Hyperactivity Disorder (ADHD) Symptoms Total Score of the Conners Adult ADHD Rating Scale (CAARS) Endpoint	26.1 units on a scale Standard Deviation 10.59	23.0 units on a scale Standard Deviation 11.07	21.6 units on a scale Standard Deviation 10.21
Attention Deficit/Hyperactivity Disorder (ADHD) Symptoms Total Score of the Conners Adult ADHD Rating Scale (CAARS) Change at Endpoint	-10.4 units on a scale Standard Deviation 11.03	-12.5 units on a scale Standard Deviation 10.38	-15.7 units on a scale Standard Deviation 10.80

SECONDARY outcome

Timeframe: from baseline to13 weeks

Population: The ITT analysis set (includes all randomized subjects) was considered the primary efficacy analysis set.

The CGI-S rating scale 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 illness). The change in CGI-S was assessed from baseline to end of treatment (week 13 or or last post-baseline assessment)

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants 2 tablets placebo once daily for 13 weeks	54 mg PR OROS MPH n=90 Participants Prolonged-release (PR) OROS methylphenidate 18 + 36 mg once daily for 13 weeks	72 mg PR OROS MPH n=92 Participants Prolonged-release (PR) OROS methylphenidate 2 tablets 36 mg once daily for 13 weeks
Change in Clinical Global Impression-Severity (CGI-S) From Baseline to End of Treatment	0.0 units on a scale Interval -6.0 to 1.0	-1.0 units on a scale Interval -4.0 to 1.0	-1.0 units on a scale Interval -4.0 to 1.0

SECONDARY outcome

Timeframe: 13 weeks

Population: The ITT analysis set (includes all randomized subjects) was considered the primary efficacy analysis set.It excludes patients for which either a baseline or end of treatment value was missing.

The CGI-C rating scale is used to rate the change in severity of the subject's illness compared to baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants 2 tablets placebo once daily for 13 weeks	54 mg PR OROS MPH n=84 Participants Prolonged-release (PR) OROS methylphenidate 18 + 36 mg once daily for 13 weeks	72 mg PR OROS MPH n=92 Participants Prolonged-release (PR) OROS methylphenidate 2 tablets 36 mg once daily for 13 weeks
Clinical Global Impression-Change (CGI-C)	3.0 units on a scale Interval 1.0 to 6.0	2.5 units on a scale Interval 1.0 to 5.0	2.0 units on a scale Interval 1.0 to 6.0

SECONDARY outcome

Timeframe: from baseline to 13 weeks

Population: The ITT analysis set (includes all randomized subjects) was considered the primary efficacy analysis set. It excludes patients for which a baseline value was missing.

The CAARS-S:S is a 26-item self-report scale that measures symptoms based on the DSM-IV criteria for ADHD. Respondents were asked to rate items pertaining to their behavior/problems using the following 4-point scale (from 0 = Not at all, never; to 3 = Very much, very frequently). The CAARS-S:S total score range is from 0 (best) to 78 (worse). The change in CAARS-S:S was assessed from baseline to end of treatment (week 13 or or last post-baseline assessment)

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants 2 tablets placebo once daily for 13 weeks	54 mg PR OROS MPH n=85 Participants Prolonged-release (PR) OROS methylphenidate 18 + 36 mg once daily for 13 weeks	72 mg PR OROS MPH n=90 Participants Prolonged-release (PR) OROS methylphenidate 2 tablets 36 mg once daily for 13 weeks
Change in Conners Adult ADHD Rating Scale Self Report Short Version (CAARS-S:S) Total Score	-8.5 units on a scale Standard Deviation 11.64	-12.8 units on a scale Standard Deviation 13.42	-12.6 units on a scale Standard Deviation 13.84

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 56 other events

Deaths: 0 deaths

54 mg PR OROS MPH

Serious events: 3 serious events

Other events: 72 other events

Deaths: 0 deaths

72 mg PR OROS MPH

Serious events: 2 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=97 participants at risk 2 tablets placebo once daily for 13 weeks	54 mg PR OROS MPH n=89 participants at risk Prolonged-release (PR) OROS methylphenidate 18 + 36 mg once daily for 13 weeks	72 mg PR OROS MPH n=92 participants at risk Prolonged-release (PR) OROS methylphenidate 2 tablets 36 mg once daily for 13 weeks
Injury, poisoning and procedural complications Concussion	0.00% 0/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	1.1% 1/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.
Injury, poisoning and procedural complications Joint Injury	1.0% 1/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.00% 0/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	1.1% 1/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.
Gastrointestinal disorders Abdominal Pain	0.00% 0/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	1.1% 1/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.
Gastrointestinal disorders Nausea	0.00% 0/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	1.1% 1/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.
Infections and infestations Cholecystitis Infective	1.0% 1/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.
Psychiatric disorders Suicidal Ideation	0.00% 0/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	1.1% 1/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.
Psychiatric disorders Suicide Attempt	0.00% 0/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	1.1% 1/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.
Reproductive system and breast disorders Ovarian Cyst Ruptured	0.00% 0/97 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	1.1% 1/89 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.	0.00% 0/92 All safety parameters were analyzed using the safety analysis set (ie all subjects who were randomized and received at least 1 dose of study medication). One subject (54mg) in the ITT analysis set was randomized but not treated. Therefore, this subject was not included in the safety analysis set.

Other adverse events

Additional Information

EMEA Medical Affairs Director

Janssen-Cilag Germany

Phone: +49 2137 955258

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60