Trial Outcomes & Findings for Placebo Controlled Trial of Dextromethorphan in Rett Syndrome (NCT NCT01520363)

NCT ID: NCT01520363

Last Updated: 2018-12-04

Results Overview

The Mullen Scales of Early Learning (MULLEN) Visual reception subscale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 57 participants
• Primary outcome timeframe: Initial evaluation and at the end of the 3 month trial
• Results posted on: 2018-12-04

Participant Flow

A total of 57 participants were consented. Of these 5 were slow metabolizers who did not meet post consent eligibility criteria.

Participant milestones

Measure	Study Drug-dextromethorphan (DM) MECP2 mutation positive subjects randomized to receive DM dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group MECP2 positive subjects randomized to the placebo compound placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.
Overall Study STARTED	26	26
Overall Study COMPLETED	24	26
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Study Drug-dextromethorphan (DM) MECP2 mutation positive subjects randomized to receive DM dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group MECP2 positive subjects randomized to the placebo compound placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Placebo Controlled Trial of Dextromethorphan in Rett Syndrome

Baseline characteristics by cohort

Measure	Study Drug-dextromethorphan (DM) n=26 Participants MECP2 mutation positive subjects randomized to receive DM dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo compound placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Total n=52 Participants Total of all reporting groups
Age, Categorical <=18 years	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	4.75 years STANDARD_DEVIATION 2.52 • n=5 Participants	4.91 years STANDARD_DEVIATION 1.91 • n=7 Participants	4.83 years STANDARD_DEVIATION 2.22 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Region of Enrollment Canada	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Mexico	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Initial evaluation and at the end of the 3 month trial

Population: Mutation positive participants who are fast metabolizers at baseline. 2 were noncompliant and removed from the study drug group. At 3 months 22 were analyzed in the study drug group and 25 in the placebo group due to incomplete data.

The Mullen Scales of Early Learning (MULLEN) Visual reception subscale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention	5.45 score on a scale Standard Deviation 3.419	6.61 score on a scale Standard Deviation 6.308	6.64 score on a scale Standard Deviation 7.135	6.57 score on a scale Standard Deviation 5.008

PRIMARY outcome

Timeframe: Baseline and 3 months

Population: Mutation positive participants who are fast metabolizers at baseline. 2 were noncompliant and removed from the study drug group. At 3 months 22 were analyzed in the study drug group and 25 in the placebo group due to incomplete data.

The Mullen Scales of Early Learning (MULLEN) Fine motor scale raw scores range from Minimum=0 to Maximum=49. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention	5.38 score on a scale Standard Deviation 5.5	7.00 score on a scale Standard Deviation 6.474	5.05 score on a scale Standard Deviation 6.103	7.04 score on a scale Standard Deviation 6.564

PRIMARY outcome

Timeframe: Baseline and 3 months

Population: Mutation positive participants who are fast metabolizers at baseline. 2 were noncompliant and removed from the study drug group. At 3 months 22 were analyzed in the study drug group and 25 in the placebo group due to incomplete data.

The Mullen Scales of Early Learning (MULLEN) Receptive Language scale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention	6.45 score on a scale Standard Deviation 5.307	6.95 score on a scale Standard Deviation 5.269	6.68 score on a scale Standard Deviation 5.472	6.55 score on a scale Standard Deviation 6.085

PRIMARY outcome

Timeframe: Baseline and 3 months

Population: Mutation positive participants who are fast metabolizers at baseline. 2 were noncompliant and removed from the study drug group. At 3 months 22 were analyzed in the study drug group and 25 in the placebo group due to incomplete data.

The Mullen Scales of Early Learning (MULLEN) Expressive Language scale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention	5.33 score on a scale Standard Deviation 3.665	6.73 score on a scale Standard Deviation 3.8	6.76 score on a scale Standard Deviation 5.504	7.29 score on a scale Standard Deviation 7.123

SECONDARY outcome

Timeframe: Baseline evaluation and at the end of the 3 month study

Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Vineland Adaptive Behavior Scales-II (VABS): Motor Skills Domain Scores individual items are scored on a Likert scale from 2=Usually, 1=Sometimes or Partially, 0= Seldom or Never. Motor Skills Domain raw scores range from: Minimum=0 to Maximum=100. A higher score is a better outcome.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention	9.86 score on a scale Standard Deviation 3.821	11.36 score on a scale Standard Deviation 4.838	9.64 score on a scale Standard Deviation 3.959	11.12 score on a scale Standard Deviation 4.755

SECONDARY outcome

Timeframe: Baseline and at the end of the 3 month trial

Population: 52 MECP2 Mutation positive participants who are fast metabolizers were enrolled in the study. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Vineland Adaptive Behavior Scales-II (VABS): Daily Living Skills Domain individual items are scored on a Likert scale from 2=Usually, 1=Sometimes or Partially, 0= Seldom or Never. The Daily Living Skills Domain measures personal behavior as well as domestic and community interaction skills. Daily Living Skills Domain raw scores range from Minimum=0 to Maximum=218.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention	21.64 score on a scale Standard Deviation 6.939	21.00 score on a scale Standard Deviation 5.307	20.95 score on a scale Standard Deviation 6.388	19.84 score on a scale Standard Deviation 4.589

SECONDARY outcome

Timeframe: Baseline and at the end of the 3 month trial

Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Vineland Adaptive Behavior Scales-II (VABS): Socialization Domain. Critical behaviors are scored on a Likert scale from 2=Usually, 1=Sometimes or Partially, 0= Seldom or Never. Socialization Domain raw scores range from: Minimum=0 to Maximum=152. A higher score is a better outcome.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention	24.14 score on a scale Standard Deviation 5.557	22.96 score on a scale Standard Deviation 4.954	24.05 score on a scale Standard Deviation 6.514	22.48 score on a scale Standard Deviation 5.524

SECONDARY outcome

Timeframe: Baseline and at the end of the 3 month trial

Population: 52 MECP2 Mutation positive participants who are fast metabolizers were enrolled at baseline. Two participants in the baseline DM group were noncompliant and removed from the study. At 3 months 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Vineland Adaptive Behavior Scales (VABS)-II Communication Domain Scores. The Communication Domain evaluates the receptive, expressive, and written communication skills of the child. Critical behaviors in each Subdomain item are rated as 2=Usually, 1=Sometimes or Partially, 0= Seldom or Never. Communication Domain raw scores range from: Minimum=0 to Maximum=198. A higher score is a better outcome.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in VABS:Communication Domain Scores, Pre- and Post-Intervention	18.05 score on a scale Standard Deviation 4.146	18.08 score on a scale Standard Deviation 4.261	17.91 score on a scale Standard Deviation 5.032	17.96 score on a scale Standard Deviation 4.835

SECONDARY outcome

Timeframe: Initial evaluation and at the end of the 3 month study. The test lasts 45 minutes

The Ghuman-Folstein Screen for Social Interaction (SSI) assesses the change in behavior and temperament dysregulation as a total score.

The score ranges from 0-162, with 0 being most Impaired /has the strongest autism features and 162 having no impairment/no autism features.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=22 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=24 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=24 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention.	73.1 units on a scale Standard Deviation 22.86	71.3 units on a scale Standard Deviation 17.26	73.1 units on a scale Standard Deviation 25.97	68.0 units on a scale Standard Deviation 16.21

SECONDARY outcome

Timeframe: Initial evaluation and at the end of the 3 month study

The Rett Syndrome Behavior Questionnaire (RSBQ) total score was assessed. The total score ranges from 0 to 90, with 0 exhibiting no Rett syndrome related symptoms and 90 showing the greatest amount of symptoms (worse outcome).

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=22 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=24 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=24 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention	33.8 units on a scale Standard Deviation 13.21	33.3 units on a scale Standard Deviation 12.26	33.8 units on a scale Standard Deviation 13.21	33.3 units on a scale Standard Deviation 12.26

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline evaluation and at the end of the 3 month study

Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Pediatric Quality of Life Inventory (PedsQL version 4). School Functioning subscale. 5-point Likert scale from 0 (Never) to 4 (Almost always); Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better Health Related Quality of Life (QOL).

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in PedsQL School Functioning Subscale Score, Pre- and Post-Intervention	64.231 score on a scale Standard Deviation 23.3682	49.583 score on a scale Standard Deviation 20.3793	55.769 score on a scale Standard Deviation 25.2782	44.592 score on a scale Standard Deviation 14.2084

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline evaluation and at the end of the 3 month study

Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Pediatric Quality of Life Inventory (PedsQL version 4) total score. Each item is rated on a 5-point Likert scale from 0 (Never) to 4 (Almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. The Total Score is the sum of all the items over the number of items answered on all the Scales. Higher scores indicate better HRQOL.

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in PedsQL Total Score, Pre- and Post-Intervention	54.018 score on a scale Standard Deviation 18.5915	54.157 score on a scale Standard Deviation 14.9519	50.9235 score on a scale Standard Deviation 19.11019	51.7286 score on a scale Standard Deviation 18.83983

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at the end of the 3 month trial

Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Pediatric Quality of Life Inventory (PedsQL version 4). Social Functioning subscale. 5-point Likert scale from 0 (Never) to 4 (Almost always); Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better Health Related Quality of Life (QOL).

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in PedsQL Social Functioning Subscale Score, Pre- and Post-Intervention	58.53 score on a scale Standard Deviation 21.849	54.64 score on a scale Standard Deviation 18.341	46.76 score on a scale Standard Deviation 16.002	47.14 score on a scale Standard Deviation 20.448

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline evaluation and at the end of the 3 month study

Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Pediatric Quality of Life Inventory (PedsQL version 4). Emotional Functioning subscale. 5-point Likert scale from 0 (Never) to 4 (Almost always); Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better Health Related Quality of Life (QOL).

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in PedsQL Emotional Functioning Subscale Score, Pre- and Post-Intervention	72.37 score on a scale Standard Deviation 17.979	68.93 score on a scale Standard Deviation 13.182	68.621 score on a scale Standard Deviation 24.3816	68.214 score on a scale Standard Deviation 113.8129

OTHER_PRE_SPECIFIED outcome

Timeframe: Initial evaluation and at the end of the 3 month study

Population: MECP2 Mutation positive participants who are fast metabolizers were randomized to placebo or DM at baseline. Two participants in the baseline DM group were noncompliant and removed from the study at baseline. At 3 months, 22 were analyzed in the DM study drug group and 25 in the placebo group due to incomplete data.

Pediatric Quality of Life Inventory (PedsQL version 4). Physical Functioning subscale. 5-point Likert scale from 0 (Never) to 4 (Almost always); Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better Health Related Quality of Life (QOL).

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=24 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=26 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=22 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=25 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in PedsQL Physical Functioning Subscale Score, Pre- and Post-Intervention	42.717 score on a scale Standard Deviation 30.3026	48.973 score on a scale Standard Deviation 29.5643	38.900 score on a scale Standard Deviation 29.7848	48.133 score on a scale Standard Deviation 34.9777

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline evaluation and at the end of the 3 month study

Population: Children enrolled at baseline aged 0 to 4 years

Change in Frequency of seizure count baseline to follow-up for children aged 0-4 years

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=11 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=10 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=11 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=10 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in Seizure Frequency, Pre- and Post-Intervention, 0-4 Year Age Group	3 seizure count Standard Deviation 1.41	3.2 seizure count Standard Deviation 1.32	3.7 seizure count Standard Deviation .90	3.1 seizure count Standard Deviation 1.45

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline evaluation and at the end of the 3 month study

Change in Frequency of seizures baseline to follow-up for children aged 5-10 years

Outcome measures

Measure	Study Drug-dextromethorphan (DM) n=13 Participants MECP2 mutation positive subjects randomized to receive DM at baseline dextromethorphan: The DM group will take 5mg/kg/day orally in 2 divided doses 12 hours apart for the 3 month period of the study. The pharmacists will dispense the DM to the study participants.	Placebo Group n=16 Participants MECP2 positive subjects randomized to the placebo at baseline placebo: The placebo will be dispensed to equal the volume of DM of 5mg/kg/day. It is taken orally in 2 divided doses 12 hours apart during the study period of 3 months. The Research pharmacist will dispense the placebo to the participants.	Study Drug Group at 3 Months n=11 Participants MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=16 Participants MECP2 mutation positive subjects randomized to placebo at 3 months
Change in Seizure Frequency, Pre-and Post-Intervention, 5-10 Year Age Group	3.6 seizure count Standard Deviation 1.19	2.8 seizure count Standard Deviation 1.47	3.36 seizure count Standard Deviation 1.12	3.37 seizure count Standard Deviation 1.20

Adverse Events

Study Drug-dextromethorphan (DM)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Study Drug Group at 3 Months

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo at 3 Months

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Study Drug-dextromethorphan (DM) n=26 participants at risk MECP2 mutation positive subjects randomized to receive dextromethorphan(DM) at baseline	Placebo Group n=26 participants at risk MECP2 positive subjects randomized to the placebo at baseline.	Study Drug Group at 3 Months n=24 participants at risk MECP2 mutation positive subjects randomized to DM at 3 months	Placebo at 3 Months n=26 participants at risk MECP2 mutation positive subjects randomized to placebo at 3 months
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	0.00% 0/26	0.00% 0/26	33.3% 8/24 • Number of events 8	42.3% 11/26 • Number of events 11
Nervous system disorders seizures	0.00% 0/26	0.00% 0/26	16.7% 4/24 • Number of events 4	30.8% 8/26 • Number of events 8
Hepatobiliary disorders Increased alkaline phosphatase	0.00% 0/26	0.00% 0/26	12.5% 3/24 • Number of events 3	3.8% 1/26 • Number of events 1
Blood and lymphatic system disorders increased platelets	0.00% 0/26	0.00% 0/26	12.5% 3/24 • Number of events 3	7.7% 2/26 • Number of events 2

Additional Information

Dr. Sakkubai Naidu

Hugo W. Moser Research Institute at Kennedy Krieger , Inc.

Phone: 443 923 2778

Email: naidu@kennedykrieger.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place