Irritability Associated With Autism Spectrum Disorder
Conditions
Brief summary
52-week, open-label extension study of double-blind study ACP-103-069 to determine the long-term safety and tolerability of pimavanserin for the treatment of irritability associated with ASD in children and adolescents (aged 5 to 17 years). ACP-103-069 is a 6-week, randomized, double-blind, fixed-dose, placebo controlled, parallel group study of pimavanserin in children and adolescents with irritability associated with autism spectrum disorder (ASD).
Detailed description
This study will be conducted as a 52-week, open-label extension study of the antecedent double-blind study to determine the long-term safety and tolerability of pimavanserin for the treatment of irritability associated with ASD in children and adolescents (5 through 17 years old at the time of enrolling into the antecedent double-blind study).
Interventions
DRUGPimavanserin
Pimavanserin given once daily, as capsule of 10, 20, or 34 mg dose strength, respectively, according to the patient's age
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Has completed the treatment period of study ACP-103-069 * Informed consent prior to the conduct of any study procedures * Continues to be both clinically stable and not at imminent risk of suicide or injury to self, others, or property * Continues to be medically stable at enrollment * For female patients only: unable to become pregnant or agree to use a highly effective non-hormonal method of contraception. Females of childbearing potential must have a negative pregnancy test
Exclusion criteria
* Patient or parent/legally accepted representative is judged by the Investigator to be inappropriate for the study * Requires treatment with a medication prohibited by the protocol, including concomitant psychotropic drugs targeting irritability, including those used off-label (clonidine, guanfacine, and propranolol; lithium, valproate), medications that prolong the QT interval; and strong cytochrome P450 (CYP) 3A4 enzyme (CYP3A4) inhibitors and inducers * At a significant risk of suicide, or is a danger to self or others * At risk of significant violent behavior to the extent that participation would pose an undue risk to other patients, caregivers, or others * Positive urine drug test * Serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies * Any change in medical or treatment status that may increase the risk associated with taking pimavanserin, would interfere with safety assessments, or would confound the interpretation of study results * Clinically significant abnormal ECG of protocol-defined cardiac conduction abnormalities * Weight \<15 kg * Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Adverse Events | 52 weeks | Number (%) of patients with treatment emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aberrant Behavior Checklist-Irritability (ABC-I) and Clinical Global Impression-Improvement (CGI-I) Response Rate | 52 weeks | The response rate was defined as the proportion of patients with at least 25% reduction from baseline to Week 52 in ABC-I and a CGI-I of irritability score of 1 (very much improved) or 2 (much improved) at Week 52, compared to baseline. Baseline was the baseline of the antecedent double-blind study APC-103-069. The ABC is a parent/caregiver-rated scale comprised of 5 subscales encompassing 58 items. Subscales are irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech. Items are rated on a 4-point Likert scale ranging from 0 (not at all a problem) to 3 (the problem is severe), with higher scores indicating more severe problems. Subscale scores are calculated by summing the items within that subscale. The CGI-I is a clinician-rated, 7-point scale to assess how much the patient's illness (here: the patient's irritability) has changed relative to baseline. Scores range from 1 (very much improved) to 7 (very much worse). |
Countries
Australia, France, Hungary, Italy, Poland, Serbia, Spain, United States
Participant flow
Recruitment details
This was an open-label extension study of the antecedent double-blind study ACP-103-069. Patients were eligible for this study if they had completed the treatment period of study ACP-103-069.
Participants by arm
| Arm | Count |
|---|---|
| Pimavanserin Pimavanserin once daily administered using age-based dosing:
* pimavanserin low dose during Weeks 1 and 2 (age 5 to 12 years: 10 mg/day; age 13 to 17 years: 20 mg/day)
* pimavanserin high dose from Week 3 onwards (5 to 12 years: 20 mg/day; 13 to 17 years: 34 mg/day) based on the investigator's assessment of clinical response Dose adjustments were allowed after Week 2 and up to Week 20, based on the investigator's assessment of clinical response and tolerability. | 209 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Lack of Efficacy | 12 |
| Overall Study | Lost to Follow-up | 10 |
| Overall Study | Noncompliance with study drug | 5 |
| Overall Study | Not further specified | 4 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Prohibited medication use | 2 |
| Overall Study | Study terminated by sponsor | 80 |
| Overall Study | Withdrawal by Subject | 20 |
Baseline characteristics
| Characteristic | Pimavanserin |
|---|---|
| Age, Continuous | 10.1 years STANDARD_DEVIATION 3.16 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants |
| Race (NIH/OMB) White | 158 Participants |
| Region of Enrollment Australia | 6 participants |
| Region of Enrollment France | 11 participants |
| Region of Enrollment Hungary | 17 participants |
| Region of Enrollment Italy | 9 participants |
| Region of Enrollment Poland | 55 participants |
| Region of Enrollment Serbia | 9 participants |
| Region of Enrollment Spain | 4 participants |
| Region of Enrollment United States | 98 participants |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 209 |
| other Total, other adverse events | 66 / 209 |
| serious Total, serious adverse events | 5 / 209 |
Outcome results
Primary
Treatment-emergent Adverse Events
Number (%) of patients with treatment emergent adverse events
Time frame: 52 weeks
Population: All patients enrolled and treated
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pimavanserin | Treatment-emergent Adverse Events | 132 Participants |
Secondary
Aberrant Behavior Checklist-Irritability (ABC-I) and Clinical Global Impression-Improvement (CGI-I) Response Rate
The response rate was defined as the proportion of patients with at least 25% reduction from baseline to Week 52 in ABC-I and a CGI-I of irritability score of 1 (very much improved) or 2 (much improved) at Week 52, compared to baseline. Baseline was the baseline of the antecedent double-blind study APC-103-069. The ABC is a parent/caregiver-rated scale comprised of 5 subscales encompassing 58 items. Subscales are irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech. Items are rated on a 4-point Likert scale ranging from 0 (not at all a problem) to 3 (the problem is severe), with higher scores indicating more severe problems. Subscale scores are calculated by summing the items within that subscale. The CGI-I is a clinician-rated, 7-point scale to assess how much the patient's illness (here: the patient's irritability) has changed relative to baseline. Scores range from 1 (very much improved) to 7 (very much worse).
Time frame: 52 weeks
Population: All patients enrolled and treated
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pimavanserin | Aberrant Behavior Checklist-Irritability (ABC-I) and Clinical Global Impression-Improvement (CGI-I) Response Rate | 51 Participants |