Prader-Willi Syndrome
Conditions
Brief summary
This was a study investigating RAD011 in participants diagnosed with Prader-Willi Syndrome (PWS). The primary objective of the Phase 2 part of this study was to assess the safety and tolerability of multiple dose levels of RAD011 in order to select 1 or 2 dose level(s) for further evaluation in the Phase 3 part of the study. In Phase 3, the primary objective was to assess the effect of RAD011 on hyperphagia-related behavior in participants with PWS.
Interventions
DRUGRAD011
Cannabidiol Oral Solution (containing synthetic cannabidiol)
DRUGPlacebo
Matching Placebo for RAD011
Sponsors
Radius Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males and females between 8 and 65 years of age (inclusive) at Screening. * Genetically confirmed diagnosis of PWS. Documentation of genetically confirmed diagnosis of PWS is acceptable. * The same caregiver is available to complete the questionnaire throughout the duration of the study. * After completion of the Tolerability period, participants will have a mean Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score ≥13 and a decrease of HQ-CT score no more than 7 during Tolerability (run-in) period. * If receiving growth hormone, psychotropic therapy, metabolic treatments that could affect appetite (including metformin), and other treatment including thyroid hormone, must be on the same medication and dose for at least 90 days prior to consent/assent
Exclusion criteria
* Known use of cannabis or cannabinoid containing products (including topical products) within 90 days prior to consent/ assent. * Use of prescription or over-the-counter weight loss agents within 90 days prior to consent/assent. * Implementation of new food or environmental restrictions within 90 days of consent/ assent. * If living in a group home, participant spends less than 25 waking hours with their caregiver per week. * Uncontrolled chronic conditions (diabetes, sleep apnea, etc.) as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 34 in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Questionnaire | Baseline, Week 34 | The HQ-CT measures hyperphagia by Prader-Willi syndrome (PWS)-specialized clinicians. The HQ-CT generates a score ranging from 0 to 36, where a higher score represents more severe abnormal food related behaviors. The change from baseline was calculated from two time points as the value at the later time point minus the value at the earlier time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 34 in Prader-Willi Syndrome (PWS)- Associated Irritability Using the Aberrant Behavior Checklist (ABC) Questionnaire - Irritability Subscale (ABC-I) | Baseline, Week 34 | The ABC questionnaire is an informant-rated questionnaire assessing severity of behavioral symptoms. The Irritability subscale of the ABC covers symptoms such as agitation, aggression, meltdowns, and self-harm. The ABC-I contains 15 items and each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score is the sum of individual items scores which ranges from 0 (no problem) to 45 (severe problem), with higher score indicating more severe condition. |
| Change From Baseline to Week 34 in Hyperphagia as Measured by the Clinician Global Impression of Change (CGI-C) | Baseline, Week 34 | The CGI-C of hyperphagia is a single-item, clinician-rated measure, assessing the clinician's impression about changes in the patient's hyperphagia condition since the start of taking the study medication at the initiation of the Tolerability Period. The CGI-C of hyperphagia utilizes a 5-point response scale: 1=Much better; 2=A little better; 3=No change; 4=A little worse; 5=Much worse. Higher scores mean a worse outcome. |
| Change From Baseline to Week 34 in Hyperphagia as Measured by the Clinician Global Impression of Severity (CGI-S) | Baseline, Week 34 | The CGI-S of hyperphagia is a single-item, clinician-rated measure, assessing the clinician's impression of the severity of a patient's hyperphagia condition. The CGI-S of hyperphagia utilizes a 5-point response scale: 1=None; 2=Mild; 3=Moderate; 4=Severe; 5=Very Severe. Higher scores mean a worse outcome. |
Countries
United States
Participant flow
Pre-assignment details
In this study, 4 participants were randomized and received at least 1 dose of study drug. No participants were randomized to the placebo group. The 4 participants were randomized in Phase 2 of the study and due to premature termination of the study, phase 3 was not conducted. None of the enrolled participants completed the study due to the study being terminated prematurely.
Participants by arm
| Arm | Count |
|---|---|
| RAD011 10 mg/kg Participants were administered 10 mg/kg of RAD011 orally daily with food. | 1 |
| RAD011 20 mg/kg Participants were administered 20 mg/kg of RAD011 orally daily with food. | 1 |
| RAD011 40 mg/kg Participants were administered 40 mg/kg of RAD011 orally daily with food. | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Early study termination | 1 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | RAD011 10 mg/kg | RAD011 20 mg/kg | RAD011 40 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | NA years | NA years | NA years | NA years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 2 |
Outcome results
Primary
Change From Baseline to Week 34 in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Questionnaire
The HQ-CT measures hyperphagia by Prader-Willi syndrome (PWS)-specialized clinicians. The HQ-CT generates a score ranging from 0 to 36, where a higher score represents more severe abnormal food related behaviors. The change from baseline was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Time frame: Baseline, Week 34
Population: Due to the premature termination of the study, no efficacy analyses were conducted. Therefore, no data was collected for this outcome measure.
Secondary
Change From Baseline to Week 34 in Hyperphagia as Measured by the Clinician Global Impression of Change (CGI-C)
The CGI-C of hyperphagia is a single-item, clinician-rated measure, assessing the clinician's impression about changes in the patient's hyperphagia condition since the start of taking the study medication at the initiation of the Tolerability Period. The CGI-C of hyperphagia utilizes a 5-point response scale: 1=Much better; 2=A little better; 3=No change; 4=A little worse; 5=Much worse. Higher scores mean a worse outcome.
Time frame: Baseline, Week 34
Population: Due to the premature termination of the study, no efficacy analyses were conducted. Therefore, no data was collected for this outcome measure.
Secondary
Change From Baseline to Week 34 in Hyperphagia as Measured by the Clinician Global Impression of Severity (CGI-S)
The CGI-S of hyperphagia is a single-item, clinician-rated measure, assessing the clinician's impression of the severity of a patient's hyperphagia condition. The CGI-S of hyperphagia utilizes a 5-point response scale: 1=None; 2=Mild; 3=Moderate; 4=Severe; 5=Very Severe. Higher scores mean a worse outcome.
Time frame: Baseline, Week 34
Population: Due to the premature termination of the study, no efficacy analyses were conducted. Therefore, no data was collected for this outcome measure.
Secondary
Change From Baseline to Week 34 in Prader-Willi Syndrome (PWS)- Associated Irritability Using the Aberrant Behavior Checklist (ABC) Questionnaire - Irritability Subscale (ABC-I)
The ABC questionnaire is an informant-rated questionnaire assessing severity of behavioral symptoms. The Irritability subscale of the ABC covers symptoms such as agitation, aggression, meltdowns, and self-harm. The ABC-I contains 15 items and each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score is the sum of individual items scores which ranges from 0 (no problem) to 45 (severe problem), with higher score indicating more severe condition.
Time frame: Baseline, Week 34
Population: Due to the premature termination of the study, no efficacy analyses were conducted. Therefore, no data was collected for this outcome measure.