Rett Syndrome
Conditions
Brief summary
To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls with Rett syndrome
Interventions
DRUGTrofinetide
Trofinetide solution of 10-30 mL based on subject's weight at Baseline, administered twice daily by mouth or gastrostomy tube (G-tube)
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
2 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
* Female subject 1. 2 to 4 years of age and body weight ≥9 kg and \<20 kg at Screening OR 2. 5 years of age and body weight ≥9 kg and \<12 kg at Screening * Can swallow the study medication provided as a liquid solution or can take it by gastrostomy tube * The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments * Has classic/typical Rett syndrome (RTT) or possible RTT according to the Rett Syndrome Diagnostic Criteria * Has a documented disease-causing mutation in the MECP2 gene * Has a stable pattern of seizures, or has had no seizures, within 8 weeks prior to Screening * Subject and caregiver(s) must reside at a location to which study drug can be delivered and have been at their present residence for at least 4 weeks prior to Screening
Exclusion criteria
* Has been treated with insulin within 12 weeks of Baseline * Has current clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus), renal, hepatic, respiratory or gastrointestinal disease (such as celiac disease or inflammatory bowel disease) or has major surgery planned during the study * Has a history of, or current, cerebrovascular disease or brain trauma * Has significant, uncorrected visual or uncorrected hearing impairment * Has a history of, or current, malignancy * Has any of the following: 1. QTcF interval of \>450 ms at Screening or Baseline 2. History of a risk factor for torsades de pointes (e.g., heart failure or family history of long QT syndrome) 3. History of clinically significant QT prolongation that is deemed to put the subject at increased risk of clinically significant QT prolongation 4. Other clinically significant finding on ECG at Screening or Baseline Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Treatment With Oral Trofinetide | Mean study drug exposure 434 days, corresponding to 1.2 years | Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), withdrawals due to AEs, potentially clinically important (PCI) changes in other safety assessments (laboratory values, vital signs, or ECGs, following protocol-defined PCI criteria) |
| AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State) | PK samples were taken predose and at Weeks 2, 4, 8, and 12 | Area under the concentration-time curve from time 0 to 12 h at steady state as obtained from population pharmacokinetic (PK) modelling |
| Cmax,ss (Maximum Observed Drug Concentration at Steady State) | PK samples were taken predose and at Weeks 2, 4, 8, and 12 | Maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling |
| Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide) | PK samples were taken predose and at Weeks 2, 4, 8, and 12 | Minimum observed drug concentration at steady state of oral trofinetide as obtained from population pharmacokinetic (PK) modeling |
| Tmax (Time of the Maximum Observed Drug Concentration at Steady State) | PK samples were taken predose and at Weeks 2, 4, 8, and 12 | Time of the maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trofinetide Trofinetide oral solution was administered twice daily for up to approximately 26 months, orally or administered by gastrostomy (G) tube. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Study drug noncompliance | 1 |
| Overall Study | Study terminated by Sponsor | 12 |
Baseline characteristics
| Characteristic | Trofinetide |
|---|---|
| Age, Continuous | 3.1 years STANDARD_DEVIATION 0.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 4 / 15 |
Outcome results
Primary
AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State)
Area under the concentration-time curve from time 0 to 12 h at steady state as obtained from population pharmacokinetic (PK) modelling
Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Population: Patients enrolled, treated, and with at least one quantifiable PK concentration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trofinetide | AUC0-12,ss (Area Under the Concentration-time Curve From Time 0 to 12 h at Steady State) | 1015.7 μg x h/mL | Standard Deviation 135.9 |
Primary
Cmax,ss (Maximum Observed Drug Concentration at Steady State)
Maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling
Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Population: Patients enrolled, treated, and with at least one quantifiable PK concentration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trofinetide | Cmax,ss (Maximum Observed Drug Concentration at Steady State) | 181.5 μg/mL | Standard Deviation 22.8 |
Primary
Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide)
Minimum observed drug concentration at steady state of oral trofinetide as obtained from population pharmacokinetic (PK) modeling
Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Population: Patients enrolled, treated, and with at least one quantifiable PK concentration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trofinetide | Cmin,ss (Minimum Observed Drug Concentration at Steady State of Oral Trofinetide) | 19.6 μg/mL | Standard Deviation 6.3 |
Primary
Safety and Tolerability of Treatment With Oral Trofinetide
Percentage of patients with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), withdrawals due to AEs, potentially clinically important (PCI) changes in other safety assessments (laboratory values, vital signs, or ECGs, following protocol-defined PCI criteria)
Time frame: Mean study drug exposure 434 days, corresponding to 1.2 years
Population: All patients enrolled and treated
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Patients with TEAEs | 14 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Patients with SAEs | 4 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Patients with AEs leading to discontinuation | 2 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Alanine transaminase ≥3 ULN | 1 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Aspartate transaminase ≥3 ULN | 1 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Potassium ≤3.0 mmol/L | 1 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Leukocytes ≥15 × 10Ê9/L | 2 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Neutrophils ≤1.5 × 10E9/L | 2 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Hematocrit <0.3 | 1 Participants |
| Trofinetide | Safety and Tolerability of Treatment With Oral Trofinetide | Hemoglobin <100 g/L | 1 Participants |
Primary
Tmax (Time of the Maximum Observed Drug Concentration at Steady State)
Time of the maximum observed drug concentration at steady state as obtained from population pharmacokinetic (PK) modelling
Time frame: PK samples were taken predose and at Weeks 2, 4, 8, and 12
Population: Patients enrolled, treated, and with at least one quantifiable PK concentration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trofinetide | Tmax (Time of the Maximum Observed Drug Concentration at Steady State) | 1.8 h | Standard Deviation 0.2 |