Open-Label Extension Study of DCCR in PWS Followed by Double-Blind, Placebo-Controlled, Randomized Withdrawal Period

An Open-Label, Long-Term Safety and Efficacy Evaluation of Diazoxide Choline Extended-Release Tablets in Participants With Prader-Willi Syndrome With a Double-Blind, Placebo-Controlled, Randomized Withdrawal Period

This is a multi-center, multi-period study with an open-label period followed by a double-blind, placebo-controlled, randomized withdrawal period evaluating the safety and efficacy of DCCR treatment.

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: DCCR; Drug: DCCR; Drug: Placebo for DCCR

Detailed Description

115 PWS participants who completed clinical study C601 will be enrolled into the OLE Period. All participants in the Open Label Extension (OLE) Period will receive open-label DCCR. The actual number of participants eligible to enroll in the double-blind, placebo-controlled, randomized withdrawal (RW) period will be limited to those participants taking DCCR in the OLE Period at the time of the RW Period Visit 1 (Baseline/Randomization Visit).The treatment groups in the C602 RW Period are those participants randomized to receive DCCR and those participants randomized to receive Placebo. Participants will be randomized in a 1:1 ratio (DCCR:Placebo).

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Women's and Children's Hospital
  • Cambridge, United Kingdom, CB21 5ER
    • Fulbourn Hospital
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital NHS Foundation Trust
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital
  • London, United Kingdom, E1 1BB
    • Royal London Hospital
  • London, United Kingdom, W12 OHS
    • Hammersmith Hospital
  • Scottland
    • Glasgow, Scottland, United Kingdom, G51 4TF
      • The Queen Elizabeth University
  • Yorkshire
    • Hull, Yorkshire, United Kingdom, HU3 2JZ
      • Hull and East Yorkshire Hospitals NHS Trust
• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine
    • Palo Alto, California, United States, 94305
      • Stanford University
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Gainesville
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Children's Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Hatfield Clinical Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Sparrow Clinical Research Institute
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Children's Minnesota
  • New Jersey
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's University Medical Center
  • New York
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43205
      • The Research Institute at Nationwide Children's Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Institute Of Dallas
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

OLE Period Key Inclusion Criteria:

• Successful completion of clinical study C601
• Provide voluntary, written informed consent (parent(s) / legal guardian(s) of patient); provide voluntary, written assent (subjects, as appropriate)

OLE Period Key Exclusion Criteria:

• Positive urine pregnancy test (in females of child-bearing potential) or females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 90 days after study participation
• Any new disease, condition, or circumstance which would prevent, in the opinion of the Investigator, the patient from completing all study visits and assessments required by the protocol (e.g., an anticipated change of care setting)

RW Period Key Inclusion Criteria:

• Provide voluntary, written informed consent (parent[s] / legal guardian[s] of participant); provide voluntary, written assent (participants, as appropriate); this includes consent for randomization and potential treatment with placebo for up to 16 weeks
• Currently participating in clinical study C602 and complete the OLE End of Treatment Visit procedures

RW Period Key Exclusion Criteria:

• Positive urine pregnancy test (in females of child-bearing potential)
• Females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 30 days after study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OLE DCCR; 75 - 525 mg DCCR	Drug: DCCR; Once daily oral administration of open-label DCCR tablet(s) during the OLE Period; Drug: DCCR; Once daily oral administration of double-blind (DCCR) tablet(s) during the RW Period
Experimental: RW DCCR; 75 - 525 mg DCCR	Drug: DCCR; Once daily oral administration of open-label DCCR tablet(s) during the OLE Period; Drug: DCCR; Once daily oral administration of double-blind (DCCR) tablet(s) during the RW Period
Placebo Comparator: RW Placebo; 75 - 525 mg Placebo for DCCR	Drug: Placebo for DCCR; Once daily oral administration of double-blind (placebo for DCCR) tablet(s) during the RW Period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the safety of DCCR by evaluating the incidence and severity of adverse events reported	Safety analyses will be conducted in all participants who receive at least one dose of DCCR. Adverse events will be described by type and level of severity.	Baseline to end of OLE (up to 4 years)
Change from RW Period Baseline in HQ-CT Total Score	Hyperphagia-related behaviors will be assessed by the hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors. The HQ-CT consists of nine items with responses ranging from 0-4 (best to worst). Scores from 9 items will be summed for a possible total score range of 0-36.	RW Period Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in HQ-CT Total Score	Hyperphagia-related behaviors will be assessed by the hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors. The HQ-CT consists of nine items with responses ranging from 0-4 (best to worst). Scores from 9 items will be summed for a possible total score range of 0-36.	Baseline to end of OLE (up to 4 years)
Change in Body Fat Mass	Change in Body Fat Mass (kg) using DXA	Baseline to end of OLE (up to 4 years)
Clinical Global Impression of Improvement (CGI-I)	CGI-I is a single statement designed to assess the Investigator's overall perception of change in the subject's condition across the course of the clinical trial. The Investigator provides a response to "Compared to the subject's condition at enrollment, the subject's condition is:" by rating the subject's behavior using a 7-point response scale (best to worst).	RW Period Week 16
Clinical Global Impression of Severity (CGI-S)	The CGI-S is a single statement designed to assess the Investigator's overall perception of the severity of the participant's illness across the course of the clinical trial. The Investigator provides a response to "Considering your total clinical experience with this particular population, how ill is this participant at this time:" by rating the subject's behavior using a 7-point response scale (best to worst).	RW Period Week 16
Assess the safety of DCCR by evaluating the incidence and severity of adverse events reported	Safety analyses will be conducted in all participants who receive at least one dose of randomized withdrawal study drug. Adverse events will be described by type and level of severity.	through the end of the RW Period, 16 weeks

Collaborators and Investigators

• Sponsor: Soleno Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): August 17, 2023
• Study Completion (Actual): August 17, 2023

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: October 19, 2018
• First Posted (Actual): October 22, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Prader-Willi Syndrome; PWS
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Overweight; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Imprinting Disorders; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: C602

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No