This study is NOT currently recruiting participants.
Number
19-CH-0026
Sponsoring Institute
National Institute of Child Health and Human Development (NICHD)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 4 Years Max Age: 100 Years
Referral Letter Required
No
Population Exclusion(s)
Non-English Speaking;Pregnant Women
Keywords
Adult; Child; Obesity; Adipose Tissue; Hyperphagia
Recruitment Keyword(s)
None
Condition(s)
Obesity; Prader-Willi Syndrome
Investigational Drug(s)
Diazoxide Choline Controlled Release
Investigational Device(s)
Intervention(s)
Drug: Diazoxide Choline Controlled Release Other: Placebo
Supporting Site
National Institute of Child Health and Human Development
The genetic disorder Prader Willi Syndrome (PWS) can cause hyperphagia. This is uncontrollable hunger that can cause overeating and obesity. Researchers want to see if diazoxide choline extended-release (DCCR) tablets help people with PWS.
Objective:
To test if DCCR tablets are safe and effective for treating hyperphagia and other PWS issues.
Eligibility:
People ages 4 years and older with Prader-Willi Syndrome with hyperphagia
Design:
Visit 1: Participants will be screened with:
-Medical history
-Physical exam
-Heart, blood, and urine tests
-Consuming a sugary drink and having small blood samples taken over 2 hours
-Swabs taken inside of the mouth
-Questions about their symptoms and behaviors
Through visit 7, some participants will take the study drug each day by mouth and some will take a placebo. None will not know which they get. At visits 1-6 they will take a dose and get a supply to take until the next visit.
Participants will keep a medication diary.
Visit 2: Participants will repeat some visit 1 procedures. Some participants will leave the study. The rest will have:
-X-ray of the body
-Questions for their caregiver and doctor
Participants may have:
-Face, back, and chest photographed
-Scan of their abdomen
-Breathing measured while in a clear plastic hood
Visits 3-6 will happen every 2 weeks. Participants will repeat some procedures.
Visit 7 will be 5 weeks after visit 6. Participants will repeat some procedures.
Some participants will join a separate study. They will have 11 more visits and take DCCR for 9 more months.
Sponsoring Institute: National Institute of Child Health and Human Development
--Back to Top--
C601 SCREENING INCLUSION CRITERIA: Potential participants must meet all of the following inclusion criteria to be enrolled: 1) Provide voluntary, written informed consent (parent(s) / legal guardian(s) of participant); provide voluntary, written assent (participants, as appropriate) 2) Male and female participants 4 years of age and older 3) Genetically-confirmed Prader-Willi syndrome. If confirmation by a method other than methylation analysis, participant and caregiver consent to methylation analysis. 4) HQ-CT score >= 13 5) In a stable care setting for at least 6 months prior to Visit 1 and throughout the study 6) Caregiver must have been caring for the participant for at least 6 months prior to Visit 1 and will care for the participant throughout the study a minimum of 4 waking hours per day 7) Participant and caregiver agree not to change dietary or physical activity regimens with a goal of weight loss. 8) Participants with a diagnosis of type II diabetes mellitus are adequately managed with a stable dose of antidiabetic medication(s) other than insulin for at least 3 months prior to Visit 1 and no recent history of ketoacidosis or hyperosmolar coma (within 6 months prior to Visit 1) 9) On stable regimens of all chronic concomitant medications for at least 3 months prior to Visit 1, except: -Treatment with growth hormone can neither stop nor start throughout the study 10) Primary caregiver must be able to communicate with Investigator and study site personnel as well as read and complete the study-required questionnaires 11) Successfully complete all screening assessments and procedures 12) At the NIH, participants must have BMI >= 30kg/m^2 (adults) or >= 95th percentile for age and sex (children 4-17.99y) according to the US Centers for Disease Control standards (1) or (for age >= 8y) have evidence for high body adiposity for age and sex (>= 75th percentile for percentage body fat) (24, 25) to be enrolled. C601 SCREENING EXCLUSION CRITERIA: Potential participants must not meet any of the following exclusion criteria to be enrolled: 1) Weight < 20 kg or >= 135 kg 2) Have participated in an interventional clinical study (i.e., use of an investigational drug or device, approved drugs or device evaluated for unapproved use) within 60 days prior to Visit 1 3) Entry of any participant s information or data into a non-interventional study and/or observational study (e.g., PATH for PWS) or PWS registry(ies) during the participant s participation in this study 4) History of allergic reaction or significant intolerance to: -Diazoxide -Thiazides -Sulfonamides 5) Use within 3 months prior to Visit 1 or anticipated requirement for use at any time during the study of the following prohibited medications: -Anti-obesity medications or other medications (including herbal preparations, over-the-counter products) or procedures for weight reduction -Medications, including homeopathy and herbal preparations, that are strong inhibitors or inducers of CYP450 1A2 or 3A4 (Refer to Flockhart Table, http://medicine.iupui.edu/CLINPHARM/ddis/clinical-table) -Medications known to prolong the QTc interval (Refer to QTDrugs List on https://crediblemeds.org/healthcare-providers/), except citalopram or escitalopram will be allowed -Systemic steroids (i.e., oral, IM, or IV) for > 7 days -Any drugs medications, herbal preparation, homeopathy, nutraceuticals, or procedures (i.e., acupuncture, vagal stimulation), that may have an effect on any study endpoints 6) Anticipate changes in caregiver, care setting or other similarly potentially disruptive changes during participation in the study 7) Known type 1 diabetes mellitus 8) Uncontrolled hypertension. 9) History of thromboembolic events (e.g., venous thrombosis, pulmonary embolism, etc.), concurrent treatment for thromboembolic event(s), and/or signs suggestive of a possible thromboembolic event 10) Known history of thromboembolic events (e.g., venous thrombosis, pulmonary embolism, etc.) in a first degree relative 11) Grade 3 or 4 peripheral edema at physical examination or history of severe peripheral edema that could not be managed with an oral diuretic 12) Positive urine pregnancy test (in females of child-bearing potential) 13) Females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 30 days after study participation 14) History of torsades de pointes (TdP), congenital long QT syndrome, bradyarrythmias, or uncompensated heart failure 15) New diagnosis of psychiatric disease within 6 months prior to Visit 1 and/or hospitalization for a psychiatric reason within 6 months prior to Visit 1 -At the NIH, diagnosis of psychiatric disease means a diagnosis at screening of schizophrenia, bipolar disorder, personality disorder or other condition based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (31) that the investigator believes will interfere significantly with study compliance will be reason for exclusion. 16) Cancer within the past 5 years (not applicable to successfully treated basal cell carcinoma and successfully treated in situ cervical cancer) prior to Visit 1 -At the NIH, cancer that leads to non-enrollment means a neoplasm with malignant potential (i.e., risk for metastasis). 17) Any other known disease and/or condition, which would prevent, in the opinion of the Investigator, the participant from completing all study visits and assessments required by the protocol 18) At the NIH, participants with pre-existing CTCAEv5.0 Grade 3 abnormalities will not be enrolled. C601 RANDOMIZATION INCLUSION CRITERIA: 1) HQ-CT score at Visit 2 is >= 13 2) Complete two-week run-in period with 80% or greater compliance 3) Continues to meet all of the screening inclusion criteria through Visit 2 4) No new medications or changes to regimens of chronic concomitant medications since Screening (Visit 1) 5) For non-diabetic participants: HbA1c < 6.5 % at Screening (Visit 1). For participants with a diagnosis of Type II diabetes mellitus: HbA1c < 8% at Screening (Visit 1) C601 RANDOMIZATION EXCLUSION CRITERIA: 1) Meet any of the screening exclusion criteria through Visit 2 2) Had QTcF (Bullet) 470 msec at Screening (Visit 1) 3) Abnormal liver function defined as aspartate aminotransferase (AST) > 3x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3x ULN and/or serum total bilirubin > 2.0 mg/dL at Screening (Visit 1) 4) Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2 and/or serum creatinine > 1.7 mg/dL at Screening (Visit 1) C602 RANDOMIZED WITHDRAWAL PERIOD INCLUSION CRITERIA: Eligible participants must meet all the following inclusion criteria to be randomized: 1) 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 2) Currently participating in clinical study C602 and complete OLE End of Treatment Visit procedures C602 RANDOMIZED WITHDRAWAL PERIOD EXCLUSION CRITERIA: Eligible participants must not meet any of the following exclusion criteria to be randomized: 1) Positive urine pregnancy test (in females of child-bearing potential) 2) Females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 30 days after study participation
Potential participants must meet all of the following inclusion criteria to be enrolled:
1) Provide voluntary, written informed consent (parent(s) / legal guardian(s) of participant); provide voluntary, written assent (participants, as appropriate)
2) Male and female participants 4 years of age and older
3) Genetically-confirmed Prader-Willi syndrome. If confirmation by a method other than methylation analysis, participant and caregiver consent to methylation analysis.
4) HQ-CT score >= 13
5) In a stable care setting for at least 6 months prior to Visit 1 and throughout the study
6) Caregiver must have been caring for the participant for at least 6 months prior to Visit 1 and will care for the participant throughout the study a minimum of 4 waking hours per day
7) Participant and caregiver agree not to change dietary or physical activity regimens with a goal of weight loss.
8) Participants with a diagnosis of type II diabetes mellitus are adequately managed with a stable dose of antidiabetic medication(s) other than insulin for at least 3 months prior to Visit 1 and no recent history of ketoacidosis or hyperosmolar coma (within 6 months prior to Visit 1)
9) On stable regimens of all chronic concomitant medications for at least 3 months prior to Visit 1, except:
-Treatment with growth hormone can neither stop nor start throughout the study
10) Primary caregiver must be able to communicate with Investigator and study site personnel as well as read and complete the study-required questionnaires
11) Successfully complete all screening assessments and procedures
12) At the NIH, participants must have BMI >= 30kg/m^2 (adults) or >= 95th percentile for age and sex (children 4-17.99y) according to the US Centers for Disease Control standards (1) or (for age >= 8y) have evidence for high body adiposity for age and sex (>= 75th percentile for percentage body fat) (24, 25) to be enrolled.
C601 SCREENING EXCLUSION CRITERIA:
Potential participants must not meet any of the following exclusion criteria to be enrolled:
1) Weight < 20 kg or >= 135 kg
2) Have participated in an interventional clinical study (i.e., use of an investigational drug or device, approved drugs or device evaluated for unapproved use) within 60 days prior to Visit 1
3) Entry of any participant s information or data into a non-interventional study and/or observational study (e.g., PATH for PWS) or PWS registry(ies) during the participant s participation in this study
4) History of allergic reaction or significant intolerance to:
-Diazoxide
-Thiazides
-Sulfonamides
5) Use within 3 months prior to Visit 1 or anticipated requirement for use at any time during the study of the following prohibited medications:
-Anti-obesity medications or other medications (including herbal preparations, over-the-counter products) or procedures for weight reduction
-Medications, including homeopathy and herbal preparations, that are strong inhibitors or inducers of CYP450 1A2 or 3A4 (Refer to Flockhart Table, http://medicine.iupui.edu/CLINPHARM/ddis/clinical-table)
-Medications known to prolong the QTc interval (Refer to QTDrugs List on https://crediblemeds.org/healthcare-providers/), except citalopram or escitalopram will be allowed
-Systemic steroids (i.e., oral, IM, or IV) for > 7 days
-Any drugs medications, herbal preparation, homeopathy, nutraceuticals, or procedures (i.e., acupuncture, vagal stimulation), that may have an effect on any study endpoints
6) Anticipate changes in caregiver, care setting or other similarly potentially disruptive changes during participation in the study
7) Known type 1 diabetes mellitus
8) Uncontrolled hypertension.
9) History of thromboembolic events (e.g., venous thrombosis, pulmonary embolism, etc.), concurrent treatment for thromboembolic event(s), and/or signs suggestive of a possible thromboembolic event
10) Known history of thromboembolic events (e.g., venous thrombosis, pulmonary embolism, etc.) in a first degree relative
11) Grade 3 or 4 peripheral edema at physical examination or history of severe peripheral edema that could not be managed with an oral diuretic
12) Positive urine pregnancy test (in females of child-bearing potential)
13) Females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 30 days after study participation
14) History of torsades de pointes (TdP), congenital long QT syndrome, bradyarrythmias, or uncompensated heart failure
15) New diagnosis of psychiatric disease within 6 months prior to Visit 1 and/or hospitalization for a psychiatric reason within 6 months prior to Visit 1
-At the NIH, diagnosis of psychiatric disease means a diagnosis at screening of schizophrenia, bipolar disorder, personality disorder or other condition based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (31) that the investigator believes will interfere significantly with study compliance will be reason for exclusion.
16) Cancer within the past 5 years (not applicable to successfully treated basal cell carcinoma and successfully treated in situ cervical cancer) prior to Visit 1
-At the NIH, cancer that leads to non-enrollment means a neoplasm with malignant potential (i.e., risk for metastasis).
17) Any other known disease and/or condition, which would prevent, in the opinion of the Investigator, the participant from completing all study visits and assessments required by the protocol
18) At the NIH, participants with pre-existing CTCAEv5.0 Grade 3 abnormalities will not be
enrolled.
C601 RANDOMIZATION INCLUSION CRITERIA:
1) HQ-CT score at Visit 2 is >= 13
2) Complete two-week run-in period with 80% or greater compliance
3) Continues to meet all of the screening inclusion criteria through Visit 2
4) No new medications or changes to regimens of chronic concomitant medications since Screening (Visit 1)
5) For non-diabetic participants: HbA1c < 6.5 % at Screening (Visit 1). For participants with a diagnosis of Type II diabetes mellitus: HbA1c < 8% at Screening (Visit 1)
C601 RANDOMIZATION EXCLUSION CRITERIA:
1) Meet any of the screening exclusion criteria through Visit 2
2) Had QTcF (Bullet) 470 msec at Screening (Visit 1)
3) Abnormal liver function defined as aspartate aminotransferase (AST) > 3x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3x ULN and/or serum total bilirubin > 2.0 mg/dL at Screening (Visit 1)
4) Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2 and/or serum creatinine > 1.7 mg/dL at Screening (Visit 1)
C602 RANDOMIZED WITHDRAWAL PERIOD INCLUSION CRITERIA:
Eligible participants must meet all the following inclusion criteria to be randomized:
1) 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
2) Currently participating in clinical study C602 and complete OLE End of Treatment Visit procedures
C602 RANDOMIZED WITHDRAWAL PERIOD EXCLUSION CRITERIA:
Eligible participants must not meet any of the following exclusion criteria to be randomized:
1) Positive urine pregnancy test (in females of child-bearing potential)
2) Females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 30 days after study participation
Principal Investigator
Referral Contact
For more information: