Trial Outcomes & Findings for A Study to Evaluate Ketamine for the Treatment of Rett Syndrome (NCT NCT03633058)
NCT ID: NCT03633058
Last Updated: 2024-05-28
Results Overview
The Number of Participants with Treatment-emergent adverse events on ketamine compared to placebo will be summarized
COMPLETED
PHASE2
23 participants
6 weeks
2024-05-28
Participant Flow
The study was conducted at 7 sites in the US with active participants between 12Mar2019 and 22Nov2021.
24 participants were screened, 23 were enrolled. 23 patients were included in the safety analysis. 21 were included in the efficacy analysis (1 was withdrawn, and 1 was excluded from analysis for study ineligibility).
Participant milestones
| Measure |
0.75 mg/kg (Placebo First, Then 0.75 mg/kg Ketamine)
placebo was dosed orally twice daily for 5 days followed by ketamine dosed orally twice daily for 5 days at 0.75 mg/kg. Dosing initiations were 14 days apart.
|
0.75 mg/kg (0.75 mg/kg Ketamine First, Then Placebo)
ketamine was dosed orally twice daily for 5 days at 0.75 mg/kg followed by placebo dosed orally twice daily for 5 days. Dosing initiations were 14 days apart.
|
1.5 mg/kg (Placebo First, Then 1.5 mg/kg Ketamine)
placebo was dosed orally twice daily for 5 days followed by ketamine dosed orally twice daily for 5 days at 0.75 mg/kg. Dosing initiations were 14 days apart.
|
1.5 mg/kg (1.5 mg/kg Ketamine First, Then Placebo)
ketamine was dosed orally twice daily for 5 days at 1.5 mg/kg followed by placebo dosed orally twice daily for 5 days. Dosing initiations were 14 days apart.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
5
|
6
|
5
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
0.75 mg/kg (Placebo First, Then 0.75 mg/kg Ketamine)
placebo was dosed orally twice daily for 5 days followed by ketamine dosed orally twice daily for 5 days at 0.75 mg/kg. Dosing initiations were 14 days apart.
|
0.75 mg/kg (0.75 mg/kg Ketamine First, Then Placebo)
ketamine was dosed orally twice daily for 5 days at 0.75 mg/kg followed by placebo dosed orally twice daily for 5 days. Dosing initiations were 14 days apart.
|
1.5 mg/kg (Placebo First, Then 1.5 mg/kg Ketamine)
placebo was dosed orally twice daily for 5 days followed by ketamine dosed orally twice daily for 5 days at 0.75 mg/kg. Dosing initiations were 14 days apart.
|
1.5 mg/kg (1.5 mg/kg Ketamine First, Then Placebo)
ketamine was dosed orally twice daily for 5 days at 1.5 mg/kg followed by placebo dosed orally twice daily for 5 days. Dosing initiations were 14 days apart.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
0
|
Baseline Characteristics
1 pt was not measured for height
Baseline characteristics by cohort
| Measure |
All Study Participants - 0.75 mg/kg Ketamine
n=11 Participants
Female patients with Rett syndrome, aged 6-12 years inclusive, who had not achieved menarche.
|
All Study Participants - 1.5 mg/kg Ketamine
n=12 Participants
Female patients with Rett syndrome, aged 6-12 years inclusive, who had not achieved menarche.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
8.6 years
STANDARD_DEVIATION 2.20 • n=11 Participants
|
7.6 years
STANDARD_DEVIATION 1.93 • n=12 Participants
|
8.1 years
STANDARD_DEVIATION 2.09 • n=23 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=11 Participants
|
12 Participants
n=12 Participants
|
23 Participants
n=23 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=11 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=23 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=11 Participants
|
1 Participants
n=12 Participants
|
1 Participants
n=23 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=11 Participants
|
11 Participants
n=12 Participants
|
22 Participants
n=23 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=11 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=23 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=11 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=23 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=11 Participants
|
1 Participants
n=12 Participants
|
1 Participants
n=23 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=11 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=23 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=11 Participants
|
0 Participants
n=12 Participants
|
1 Participants
n=23 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=11 Participants
|
11 Participants
n=12 Participants
|
20 Participants
n=23 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=11 Participants
|
0 Participants
n=12 Participants
|
1 Participants
n=23 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=11 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=23 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=11 Participants
|
12 participants
n=12 Participants
|
23 participants
n=23 Participants
|
|
Weight
|
24.4 kg
STANDARD_DEVIATION 7.33 • n=11 Participants
|
21.5 kg
STANDARD_DEVIATION 4.62 • n=12 Participants
|
22.9 kg
STANDARD_DEVIATION 6.10 • n=23 Participants
|
|
Height
|
126.0 cm
STANDARD_DEVIATION 11.84 • n=11 Participants • 1 pt was not measured for height
|
117.5 cm
STANDARD_DEVIATION 9.41 • n=11 Participants • 1 pt was not measured for height
|
121.7 cm
STANDARD_DEVIATION 11.30 • n=22 Participants • 1 pt was not measured for height
|
|
BMI
|
15.1 kg/m^2
STANDARD_DEVIATION 3.06 • n=11 Participants • 1 pt was not measured for height and BMI could not be calculated
|
15.4 kg/m^2
STANDARD_DEVIATION 1.89 • n=11 Participants • 1 pt was not measured for height and BMI could not be calculated
|
15.2 kg/m^2
STANDARD_DEVIATION 2.48 • n=22 Participants • 1 pt was not measured for height and BMI could not be calculated
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: The Safety Population consisted of all patients who received at least 1 dose of study treatment.
The Number of Participants with Treatment-emergent adverse events on ketamine compared to placebo will be summarized
Outcome measures
| Measure |
0.75 mg/kg Ketamine
n=11 Participants
ketamine was dosed orally twice daily for 5 days at 0.75 mg/kg and placebo was dosed orally twice daily for 5 days. Dose initiations were 14 days apart. AEs reported occurred while patients were on ketamine.
|
0.75 mg/kg Placebo
n=11 Participants
placebo was dosed orally twice daily for 5 days and ketamine was dosed orally at 0.75 mg/kg twice daily for 5 days. Dose initiations were 14 days apart. AEs reported occurred while patients were on placebo.
|
1.5 mg/kg Ketamine
n=12 Participants
ketamine was dosed orally twice daily for 5 days at 1.5 mg/kg and placebo was dosed orally twice daily for 5 days. Dose initiations were 14 days apart. AEs reported occurred while patients were on ketamine.
|
1.5 mg/kg Placebo
n=12 Participants
placebo was dosed orally twice daily for 5 days and ketamine was dosed orally at 1.5 mg/kg twice daily for 5 days. Dose initiations were 14 days apart. AEs reported occurred while patients were on placebo.
|
|---|---|---|---|---|
|
Dose-Limiting Adverse Events
TEAEs
|
2 Participants
|
4 Participants
|
6 Participants
|
3 Participants
|
|
Dose-Limiting Adverse Events
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Dose-Limiting Adverse Events
AEs leading to discontinuation
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Dose-Limiting Adverse Events
AEs leading to dose interruption
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Dose-Limiting Adverse Events
No TEAEs reported
|
9 Participants
|
7 Participants
|
5 Participants
|
9 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6-8 weeks2 different non-invasive, wearable devices will be used in the study to determine changes in physiologic measures for the patient in the home environment. Biosensors will be worn continuously during the screening and treatment period to measure activity, sleep, position, heart rate, and breathing.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksClinicians will use a 7 point Likert Scale to rate change from baseline symptom severity by addressing the question, "Compared to the patient's condition of Rett syndrome prior to treatment initiation at baseline, the patient's current condition is: 1 very much improved, 2 much improved, 3 minimally improved, 4 no change, 5 minimally worse, 6 much worse, 7 very much worse. No change would be scored a 0, while improvement would be scored at -1, -2, or -3 and worsening would be scored +1, +2 or +3, depending on the degree of perceived change. Negative change indicates improvement while positive change indicates worsening
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksa 37-item questionnaire for clinicians to evaluate current behavioral/social, orofacial/respiratory, and motor/physical symptoms. Each item is rated either 0 (normal or never), 1 (mild or rare), 2 (moderate or occasional), 3 (marked or frequent), 4 (very severe or constant), where higher numbers indicate higher severity. Each subscale is summed for a subscale score, while the total score is a sum of the subscale scores. The behavioral/social subscale score may range from 0 to 64; the orofacial/respiratory subscale may range from 0 to 28, and motor/physical subscale may range from 0 to 56. Total score may range from 0 to 148.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksan 8 category (domain) questionnaire to assess current hand function, walking, verbal and non-verbal communication, comprehension, attention, behavior problems, and mood by considering the question, "Considering your experience with the patient at this visit, please rate the level of function in each category". Each domain will be rated on a 7 point Likert Scale where the clinician will select 1 of 7 choices: 1 normal, 2 borderline abnormal, 3 mildly abnormal, 4 moderately abnormal, 5 markedly abnormal, 6 severely abnormal, 7 extremely abnormal. Lower values indicate lesser severity while higher values indicate higher severity.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksa 45-item questionnaire for clinicians to evaluate current behavior and emotional features. Each item is rated either 0 (not true or not done), 1 (somewhat or sometimes true) and 2 (very true), where higher numbers indicate higher severity. Total score is summed and may range from 0 to 90.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksa 9 category (domain) questionnaire to assess current hand function, walking, verbal and non-verbal communication, comprehension, attention, behavior problems, mood, and seizure activity, by considering the question, "Considering your experience with your child over the past 7 days, please rate your child's level of function in each category". Each domain will be rated on a 7 point Likert Scale where the parent/caregiver will select 1 of 7 choices: 1 normal, 2 borderline abnormal, 3 mildly abnormal, 4 moderately abnormal, 5 markedly abnormal, 6 severely abnormal, 7 extremely abnormal. Lower values indicate lesser severity while higher values indicate higher severity.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksa 35-item questionnaire for parents to evaluate current sleep and common sleep problems. The parent/caregiver will rate each item as 1 (rarely), 2 (sometimes), or 3 (usually), where higher scores indicate higher severity. The parent/caregiver will also indicate if the item is a problem or not. A total score of the sum of each item and 8 subscale scores (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness) are possible. Total scores between 0 and 70 are possible, where higher scores indicate more sleep problems.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksa 26-item questionnaire for parents to evaluate the burden of care on their quality of life. The parent/caregiver will rate each item as 0 (never), 1 (rarely), 2 (sometimes), 3 (quite frequently), or 4 (nearly always) where higher scores indicate higher severity. Total scores between 0 and 104 are possible, where higher scores indicate more caregiver burden.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1, Day 15ketamine EEG alpha, beta, gamma, delta and theta waveform signatures compared to placebo to indicate target engagement
Outcome measures
Outcome data not reported
Adverse Events
0.75 mg/kg Ketamine
0.75 mg/kg Placebo
1.5 mg/kg Ketamine
1.5 mg/kg Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
0.75 mg/kg Ketamine
n=11 participants at risk
AEs reported while on ketamine in the 0.75 mg/kg cohort
|
0.75 mg/kg Placebo
n=11 participants at risk
AEs reported while on placebo in the 0.75 mg/kg cohort
|
1.5 mg/kg Ketamine
n=12 participants at risk
AEs reported while on ketamine in the 1.5 mg/kg cohort
|
1.5 mg/kg Placebo
n=12 participants at risk
AEs reported while on placebo in the 1.5 mg/kg cohort
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/11 • 6 weeks
|
9.1%
1/11 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
1/11 • Number of events 1 • 6 weeks
|
9.1%
1/11 • Number of events 1 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
General disorders
Pyrexia
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
Infections and infestations
Ear infection
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Injury, poisoning and procedural complications
Stoma site irritation
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Metabolism and nutrition disorders
decreased appetite
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Nervous system disorders
drooling
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
Nervous system disorders
sedation
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Nervous system disorders
Somnolence
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
Nervous system disorders
Tonic convulsion
|
0.00%
0/11 • 6 weeks
|
9.1%
1/11 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/11 • 6 weeks
|
9.1%
1/11 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Psychiatric disorders
Irritability
|
0.00%
0/11 • 6 weeks
|
9.1%
1/11 • Number of events 1 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
9.1%
1/11 • Number of events 1 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/11 • 6 weeks
|
0.00%
0/11 • 6 weeks
|
8.3%
1/12 • Number of events 1 • 6 weeks
|
0.00%
0/12 • 6 weeks
|
Additional Information
Jeffrey L. Neul, MD, PhD, Principal Investigator
Vanderbilt University Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place