Trial Outcomes & Findings for Clinical Efficacy & Safety, of Metadoxine (MG01CI) Extended Release in Attention-Deficit Hyperactivity Disorder (ADHD) (NCT NCT01243242)

Last Updated: 2012-04-20

Results Overview

The primary efficacy endpoint is the difference in change (decrease) in CAARS (Total ADHD Symptoms Score) between the study groups. The CAARS assess the presence and severity of ADHD symptoms and behaviors in adults. Respondents are asked to report their own experiences by rating items pertaining to their behavior/problems using a 4-point Likert-style format ranging from 0 ('Not at all', 'never') to 3 ('Very much', 'very frequently'). The scale measures ADHD symptoms using a 30-item questionnaire.Total score is the sum of all the items ,min=30 Max=90

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

120 participants

Primary outcome timeframe

6 weeks (from visit 1 baseline to visit 6)

Results posted on

2012-04-20

Participant Flow

subjects recruitment was done in two medical centers Geha and Rambam during Feb 2011-June 2011.

subjects were screened for study eligibility according to the inclusion exclusion criteria. Each subject underwent a battery of rating scales including confirmation of ADHD diagnosis and exclusion of other psychological disorders.In addition medical history was checked and lab test and Electrocardiogram (ECG) were preformed.

Participant milestones

Participant milestones
Measure	METADOXINE(MG01CI) Eligible subjects who received 1400 mg of Metadoxine	Placebo Eligible subjects who received 1400 mg of Placebo
Overall Study STARTED	60	60
Overall Study COMPLETED	57	56
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	METADOXINE(MG01CI) Eligible subjects who received 1400 mg of Metadoxine	Placebo Eligible subjects who received 1400 mg of Placebo
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	1	1
Overall Study Physician Decision	0	1
Overall Study sponsor decision	0	1
Overall Study non compliance	1	0

Baseline Characteristics

Clinical Efficacy & Safety, of Metadoxine (MG01CI) Extended Release in Attention-Deficit Hyperactivity Disorder (ADHD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	METADOXINE(MG01CI) n=60 Participants Eligible subjects who received 1400 mg of Metadoxine	Placebo n=60 Participants Eligible subjects who received 1400 mg of Placebo	Total n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	60 Participants n=5 Participants	60 Participants n=7 Participants	120 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	21 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	39 Participants n=7 Participants	73 Participants n=5 Participants
Region of Enrollment Israel	60 participants n=5 Participants	60 participants n=7 Participants	120 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks (from visit 1 baseline to visit 6)

Population: The ITT population included all randomized subjects who completed at least one post-randomization visit.

Outcome measures

Outcome measures
Measure	METADOXINE(MG01CI) n=58 Participants Eligible subjects who received 1400 mg of Metadoxine	Placebo n=59 Participants Eligible subjects who received 1400 mg of Placebo
Conners' Adult ADHD Rating Scales (CAARS™)	-12 units on a scale Standard Deviation 9.69	-8.93 units on a scale Standard Deviation 9.26

SECONDARY outcome

Timeframe: 6 weeks( visit 1 baseline to visit 6)

Population: The ITT population included all randomized subjects who completed at least one post-randomization visit.

The TOVA is a computerized test that provides information about an individual's sustained attention, speed and consistency of responding, and behavioral self-regulation and executive functioning. ADHD score is a comparison of the subject's response to the CPT test to those of an ADHD group, and is reported as a Z-score. An ADHD score of -1.80 and less fits the profile of the ADHD sample. A score of more than -1.80 (more positive) does not fit the ADHD profile. When comparing ADHD scores the higher the ADHD score the better the performance.

Outcome measures

Outcome measures
Measure	METADOXINE(MG01CI) n=58 Participants Eligible subjects who received 1400 mg of Metadoxine	Placebo n=59 Participants Eligible subjects who received 1400 mg of Placebo
Test of Variables of Attention (TOVA) (Change in ADHD Score From Screening to Visit 6)	4.96 Z score Standard Deviation 8.86	3.01 Z score Standard Deviation 6.40

SECONDARY outcome

Timeframe: 6 weeks (from visit 1 baseline to visit 6)

Population: The ITT population included all randomized subjects who completed at least one post-randomization visit

The AAQoL scale provides a validated disease-specific measure of the impact of ADHD on quality of life.It is scored as an overall score (29 items) and four subscale scores: life productivity (11 items), psychological health (6 items), life outlook (7 items) and relationships (5 items). Individual items are scored on a five-point Likert-like scale from 'Not at all/Never' (1) to 'Extremely/Very Often' (5).

Outcome measures

Outcome measures
Measure	METADOXINE(MG01CI) n=58 Participants Eligible subjects who received 1400 mg of Metadoxine	Placebo n=59 Participants Eligible subjects who received 1400 mg of Placebo
Adult ADHD Quality of Life (AAQoL)- Measuring Change in Total Score of AAQoL From Visit 1 to Visit 6	10.93 units on a scale Standard Deviation 11.1	5.71 units on a scale Standard Deviation 15.82

SECONDARY outcome

Timeframe: 6 weeks from visit 1 baseline to visit 6

Population: The ITT population included all randomized subjects who completed at least one post-randomization visit. During the conduct of the study, CGI-I evaluations were not done correctly and thus data interpretation is limited.

The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-I scores range from 1 ('very much improved') through to 7 ('very much worse'). During the conduct of the study, CGI-I evaluations were not done correctly and thus data interpretation is limited.

Outcome measures

Outcome data not reported

Adverse Events

METADOXINE(MG01CI)

Serious events: 1 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	METADOXINE(MG01CI) n=58 participants at risk Eligible subjects who received 1400 mg of Metadoxine	Placebo n=59 participants at risk Eligible subjects who received 1400 mg of Placebo
Infections and infestations Appendicitis	1.7% 1/58 • Number of events 1 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	1.7% 1/58 • Number of events 1 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)

Other adverse events

Additional Information

Dr Yaron Daniely CEO

Alcobra

Phone: 972-072-2204662

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	METADOXINE(MG01CI) n=58 participants at risk Eligible subjects who received 1400 mg of Metadoxine	Placebo n=59 participants at risk Eligible subjects who received 1400 mg of Placebo
Gastrointestinal disorders Abdominal pain upper	8.6% 5/58 • Number of events 6 • 8 weeks (from time of informed consent to end of study)	5.1% 3/59 • Number of events 3 • 8 weeks (from time of informed consent to end of study)
General disorders Asthenia	3.4% 2/58 • Number of events 2 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Musculoskeletal and connective tissue disorders Back pain	6.9% 4/58 • Number of events 4 • 8 weeks (from time of informed consent to end of study)	5.1% 3/59 • Number of events 3 • 8 weeks (from time of informed consent to end of study)
Infections and infestations Bacteriuria	3.4% 2/58 • Number of events 2 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Metabolism and nutrition disorders Decreased appetite	3.4% 2/58 • Number of events 2 • 8 weeks (from time of informed consent to end of study)	1.7% 1/59 • Number of events 1 • 8 weeks (from time of informed consent to end of study)
Psychiatric disorders Disturbance in attention	3.4% 2/58 • Number of events 4 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Nervous system disorders Dizziness	5.2% 3/58 • Number of events 3 • 8 weeks (from time of informed consent to end of study)	1.7% 1/59 • Number of events 1 • 8 weeks (from time of informed consent to end of study)
Reproductive system and breast disorders Dysmenorrhoea	3.4% 2/58 • Number of events 4 • 8 weeks (from time of informed consent to end of study)	6.8% 4/59 • Number of events 5 • 8 weeks (from time of informed consent to end of study)
General disorders Fatigue	5.2% 3/58 • Number of events 3 • 8 weeks (from time of informed consent to end of study)	1.7% 1/59 • Number of events 1 • 8 weeks (from time of informed consent to end of study)
Nervous system disorders Headache	29.3% 17/58 • Number of events 22 • 8 weeks (from time of informed consent to end of study)	39.0% 23/59 • Number of events 24 • 8 weeks (from time of informed consent to end of study)
Psychiatric disorders Impatience	3.4% 2/58 • Number of events 2 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Psychiatric disorders Initial insomnia	5.2% 3/58 • Number of events 3 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Nervous system disorders Memory impairment	3.4% 2/58 • Number of events 4 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Gastrointestinal disorders Nausea	17.2% 10/58 • Number of events 13 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Psychiatric disorders Nervousness	3.4% 2/58 • Number of events 2 • 8 weeks (from time of informed consent to end of study)	1.7% 1/59 • Number of events 1 • 8 weeks (from time of informed consent to end of study)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.6% 5/58 • Number of events 5 • 8 weeks (from time of informed consent to end of study)	6.8% 4/59 • Number of events 5 • 8 weeks (from time of informed consent to end of study)
General disorders Pyrexia	3.4% 2/58 • Number of events 2 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Infections and infestations Urinary tract infection	3.4% 2/58 • Number of events 2 • 8 weeks (from time of informed consent to end of study)	0.00% 0/59 • 8 weeks (from time of informed consent to end of study)
Gastrointestinal disorders Vomiting	3.4% 2/58 • Number of events 2 • 8 weeks (from time of informed consent to end of study)	1.7% 1/59 • Number of events 1 • 8 weeks (from time of informed consent to end of study)