Hyperphagia related behavior associated with Prader-Willi Syndrome MedDRA version: 20.0 Level: PT Classification code 10020710 Term: Hyperphagia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: RAD011
Product Code: RAD011
Pharmaceutical Form: Oral solution in bottle
INN or Proposed INN: Cannabidiol
CAS Number: 13956-29-1
Concentration unit: mg/ml milligram(s)/millilitre
Concent
Sponsors
Radius Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Presence of a parent/legal guardian that is able to consent for their participation. Parent/caregiver/legal guardian can complete the required assessments throughout the study. Patient consent/assent will be obtained if the patient is 8 years of age or older and has the mental capacity to understand and sign a written consent/assent form and/or give verbal assent 2. Males and females between: a. Phase 2: 12 and 65 years of age (inclusive) at time of consent/assent b. Phase 3: 8 and 65 years of age (inclusive) at time of consent/assent 3. Documentation of genetically confirmed PWS diagnosis 4. If a caregiver helps in completing the HQ-CT or other questionnaires, the same caregiver is available to complete the questionnaire throughout the duration of the study 5. If female, is either not of childbearing potential (defined as premenarchal or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or practicing one of the following medically acceptable methods of birth control up to 4 weeks after the last dose of RAD011 or placebo: a. Double barrier method (i.e., condom plus occlusive cap (diaphragm or cervical/vault caps), condom or occlusive cap plus spermicide b. Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives at a stable dose for a minimum of 1 full cycle (based on the patient’s usual menstrual cycle period) before IP administration c. Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) d. If not using hormonal contraceptives or IUD or IUS, then all male partners throughout the study must have been vasectomized and have received medical assessment of the surgical success 6. If male, is vasectomized and has received medical assessment of the surgical success or agrees to use an approved method of contraception (double barrier method as described in Inclusion Criterion 5, female partner’s use of an IUD or IUS [in place at least 12 weeks prior to dosing], oral contraceptives or female partner who is surgically sterile or 2 years postmenopausal) and agrees to use this method for 4 weeks after last administration of RAD011 or placebo 7. If receiving growth hormone (GH), psychotropic therapy, metabolic treatments that could affect appetite (including metformin), and other treatment including thyroid hormone, must be on the same medication and stable dose for at least 90 days prior to consent/assent 8. Any non-medical interventions (eg, counseling, behavior modification) should be stable for at least 90 days prior to consent/assent 9. HQ-CT eligibility automatically calculated in the electronic data capture (EDC) system: a. Visit 2 i. Patients with a mean HQ-CT score =13 (from Visit 1 and Visit 2) will be eligible to continue in the Tolerability Period b. Visit 5 i. Patients with a mean HQ-CT score =13 (from Visit 3, Visit 4 and Visit 5) will be eligible for randomization, and ii. Patients with a decrease in HQ-CT score (from Tolerability Period to the Screening Period) =7 will be eligible for randomization Are the trial subjects under 18? yes Number of subjects for this age range: 163 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 28 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Hypersensitivity or intolerance to CBD, or any other excipients used in the RAD011 preparation 2. Known use of cannabis or cannabinoid containing products (including topical products) within 90 days prior to consent/assent 3. History of chronic liver disease, such as cirrhosis or chronic hepatitis due to any cause 4. Positive urine test for drugs of abuse, including tetrahydrocannabinol (THC), or known history of drug, alcohol, or substance abuse 5. Use of prescription or over-the-counter weight loss agents within 90 days prior to consent/assent 6. Implementation of new food restrictions or environmental restrictions within 90 days of consent/assent 7. Any significant comorbid condition or disease: a. Respiratory disease, heart disease, or psychiatric disorder which in the opinion of the Investigator would preclude the patient from participating or b. Uncontrolled type 1 or type 2 diabetes as determined by the Investigator or c. Clinically significant ECG abnormalities or other evidence of clinically significant heart disease as determined by the Investigator or d. Uncontrolled sleep apnea as determined by the Investigator or e. Neutropenia with neutrophil counts 439 msec b. For males aged 20 to 65 years: QTcF >450 msec c. For females aged 20 to 65 years; QTcF >470 msec 9. At consent/assent, patients with age-matched hypertensive levels of systolic and/or diastolic blood pressure may be excluded at the Investigator’s discretion if deemed to be in the best interest of the patient. 10. Pregnant (determined by a positive serum pregnancy test) or lactating female 11. Unwillingness or inability to follow the procedures outlined in the protocol 12. Estimated glomerular filtration rate 1.5 × upper limit of normal (ULN), or aspartate aminotransferase (AST), alanine aminotransferase (ALT) >3 × ULN, or international normalized ratio (INR) >1.5 × ULN 14. Patient judged by the Investigator or Sponsor (or designee) as unable to comply with the treatment protocol, including appropriate supportive care, follow up, and research tests 15. Other genetic, hormonal, chromosomal, cognitive, or behavioral impairment 16. If living in a group home, patient spends less than 25 waking hours with their caregiver per week 17. Significant risk of committing suicide based on history, routine psychiatric examination, or based on the Investigator's judgment 18. Participation in any other study involving an investigational product or device within 4 weeks or 5 half-lives (whichever is longer) of consent/assent or longer as required by local regulations
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 2 Part: The primary objective of the Phase 2 part of this study is to assess the safety and tolerability of multiple doses levels of RAD011 in order to select 1 or 2 dose level(s) to further evaluate in the Phase 3 part of the study. Phase 3 Part: The primary objective of the Phase 3 part of this study is to assess the effect of RAD011 on hyperphagia-related behavior in patients with PWS.;Secondary Objective: The secondary objectives are to assess the following: - Effect of RAD011 on irritability - Effect of RAD011 on Clinician Global Impression of Change (CGI-C) in Hyperphagia - Effect of RAD011 on Clinician Global Impression of Severity(CGI-S) of Hyperphagia - Safety and tolerability of RAD011. Other objectives of this study are to assess the following: - Effect of RAD011 on Caregiver Global Impression of Change (CaGI-C) in Hyperphagia - Effect of RAD011 on Caregiver Global Impression of Severity (CaGI-S) of Hyperphagia - Effect of RAD011 on Caregiver Global Impression of Change (CaGI-C) in Irritability - Effect of RAD011 on overall behavior - Effect of RAD011 on sleep - Effect of RAD011 on body mass index (BMI) and weight - Effect of RAD011 on skin-picking behavior - Effect of RAD011 on total muscle/fat composition (performed at selected US sites).;Primary end point(s): - Change in HQ-CT scores from Baseline through End of Study/Week 34 Visit for RAD011 compared to placebo;Timepoint(s) of evaluation of this end point: From Baseline through End of Study/Week 34 Visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in PWS-associated Irritability from Baseline through End of Study/Week 34 Visit using the Aberrant Behavior Checklist (ABC) questionnaire – Irritability subscale (ABC-I) for RAD011 compared to placebo - Change in hyperphagia as defined by the Clinician Global Impression of Change (CGI-C) in Hyperphagia through End of Study/Week 34 Visit - Change in Clinician Global Impression of Severity (CGI-S) of Hyperphagia Scale from Baseline through End of Study/Week 34 Visit;Timepoint(s) of evaluation of this end point: From Baseline through End of Study/Week 34 Visit for all secondary endpoints. | — |
Countries
Australia, Canada, France, Italy, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Operations
Radius Pharmaceuticals, Inc.
Outcome results
None listed