A Study of Diazoxide Choline in Patients With Prader-Will... | NCT03440814

Status Module

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
DCCR	Experimental	75 - 450 mg DCCR	Drug: DCCR
Placebo	Placebo Comparator	75 - 450 mg placebo for DCCR	Drug: Placebo for DCCR

Name	Type	Description	Arm Group Labels	Other Names
DCCR	Drug	Once daily oral administration	DCCR
Placebo for DCCR

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13)	Hyperphagia-related behaviors were assessed by the validated hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors that was completed by the caregiver. The HQ-CT consists of nine items with responses ranging from 0-4 units each (possible total score range: 0-36). The HQ-CT was assessed at Screening, Baseline (Visit 2), and approximately every 4 weeks post-dose at Week 4, Week 8, and Week 13. A decrease in score from baseline represented improvement.	Baseline to Visit 7 (Week 13)

Secondary Outcomes

Measure	Description	Time Frame
Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13)	The Clinical Global Impression of Improvement (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 provided 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: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, and Very much worse. The Investigator only took into account the subject's PWS condition.

Eligibility Module

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Evelien Gevers, MD, PhD	Queen Mary University of London, Barts Health NHS Trust	Principal Investigator
Jennifer L. Miller, MD	University of Florida	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of California, Irvine		Orange	California	92868	United States
Stanford University

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38671361	Derived	Strong TV, Miller JL, McCandless SE, Gevers E, Yanovski JA, Matesevac L, Bohonowych J, Ballal S, Yen K, Hirano P, Cowen NM, Bhatnagar A. Behavioral changes in patients with Prader-Willi syndrome receiving diazoxide choline extended-release tablets compared to the PATH for PWS natural history study. J Neurodev Disord. 2024 Apr 26;16(1):22. doi: 10.1186/s11689-024-09536-x.
37919617

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 11, 2019

Arm/Group Information

ID	Title	Description
BG000	DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved.
BG001	Placebo for DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg placebo for DCCR tablets could be taken; Placebo was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the Placebo group were titrated on placebo, similar to the DCCR group.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00013.2(4 to 40) BG00113.6(5 to 44) BG00213.4(4 to 44)

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

<8 years

Title	Measurements
	BG00018 BG0017 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00047 BG00123 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0006 BG0017 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG0001 BG0010 BG002

HQ-CT Total Score

Hyperphagia-related behaviors were assessed by the validated hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors that was completed by the caregiver. The HQ-CT consists of nine items with responses ranging from 0-4 units each (possible total score range: 0-36). The HQ-CT was assessed at Screening, Baseline (Visit 2), and approximately every 4 weeks post-dose at Week 4, Week 8, and Week 13. A decrease in score from baseline represented improvement.

Mean

Standard Deviation

score on a scale

Title

Denominators

Categories

Title	Measurements
	BG00023.0± 6.01 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13)

Intent to treat (ITT) population includes all randomized subjects who had a Baseline HQ-CT value and at least one post-Baseline HQ-CT value.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Visit 7 (Week 13)

ID	Title	Description
OG000	DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved.
OG001	Placebo for DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg placebo for DCCR tablets could be taken; Placebo was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the Placebo group were titrated on placebo, similar to the DCCR group.

Units	Counts
Participants	OG00082 OG00142

Title

Denominators

Categories

Title	Measurements
	OG000-5.94± 0.879 OG001-4.27± 1.145

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	MMRM analysis adjusted for baseline growth hormone use and HQ-CT total score. All available subject data were used with no imputation of missing data.	0.1983		Mean Difference (Final Values)	-1.67	Standard Error of the Mean	1.294	2-Sided	95	-4.24	0.89			alpha=0.05 level of significance		Superiority

Secondary

Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13)

The Clinical Global Impression of Improvement (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 provided 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: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, and Very much worse. The Investigator only took into account the subject's PWS condition.

Intent to treat (ITT) population includes all randomized subjects who had a Baseline HQ-CT value and at least one post-Baseline HQ-CT value

Posted

Count of Participants

Participants

at Visit 7 (Week 13)

ID	Title	Description
OG000	DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved.
OG001	Placebo for DCCR

Secondary

Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13)

The Caregiver Global Impression of Change (GI-C) is a single statement designed to assess the caregiver's overall perception of change in the subject across the course of the clinical trial. The caregiver provided a response to "Please choose the response below that best describes the overall change in the person's PWS since they started taking the study medication" using a 7-point graded response scale: Very much better, Moderately better, A little better, No change, A little worse, Moderately worse, and Very much worse.

Intent to treat (ITT) population includes all randomized subjects who had a Baseline HQ-CT value and at least one post-Baseline HQ-CT value.

Posted

Count of Participants

Participants

at Visit 7 (Week 13)

ID	Title	Description
OG000	DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved.
OG001	Placebo for DCCR

Secondary

Change in Fat Mass (kg) From Baseline at Visit 7 (Week 13)

Whole body scans were performed. Reports included a breakdown of the following regions: left arm, right arm, trunk, left leg, right leg, and head. Each region was evaluated for body fat mass (g).

Intent to treat (ITT) population includes all randomized subjects who had a Baseline HQ-CT value and at least one post-Baseline HQ-CT value.

Posted

Least Squares Mean

Standard Error

Baseline to Visit 7 (Week 13)

ID	Title	Description
OG000	DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved.
OG001	Placebo for DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg placebo for DCCR tablets could be taken; Placebo was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the Placebo group were titrated on placebo, similar to the DCCR group.

Post-Hoc

Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13) - Pre-COVID Analysis

The pre-COVID analysis population consisted of all subjects who had at least one post-baseline assessment of HQ-CT prior to March 1, 2020, when a national emergency was declared in the US as a result of the COVID-19 pandemic.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Visit 7 (Week 13)

ID	Title	Description
OG000	DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved.	0	84	6	84	69	84
EG001	Placebo for DCCR	Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg placebo for DCCR tablets could be taken; Placebo was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed. The target dose by weight (kg) was as follows: Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the Placebo group were titrated on placebo, similar to the DCCR group.	0	42	0	42	31	42

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected84 at risk EG0010 events0 affected42 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected42 at risk
Staphylococcal infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected42 at risk
Abnormal behaviour	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected42 at risk
Aggression	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected42 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected42 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected42 at risk
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected42 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected42 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertrichosis	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00032 events30 affected84 at risk EG0016 events6 affected42 at risk
Hirsutism	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0008 events6 affected84 at risk EG0016 events3 affected42 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0009 events9 affected84 at risk EG0017 events5 affected42 at risk
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG00028 events16 affected84 at risk EG0014 events4 affected42 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG0006 events5 affected84 at risk EG0010 events0 affected42 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0014 events4 affected42 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0015 events3 affected42 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0005 events5 affected84 at risk EG00114 events6 affected42 at risk
Blood glucose increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0005 events5 affected84 at risk EG0012 events2 affected42 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00010 events10 affected84 at risk EG0010 events0 affected42 at risk

All subjects were enrolled and had baseline visits prior to the COVID-19 pandemic; however, there was a subset of subjects who needed to complete some of their visits after the onset of the pandemic. The pandemic forced numerous restrictions on normal activities and involved significant disruptions, which had a substantially adverse but inconsistent effect on the study conduct and results. For this reason, the ITT population - Pre-COVID analysis includes all data through March 1, 2020.

Certain Agreements

Ancestor Terms

ID	Term
D008607	Intellectual Disability
D019954	Neurobehavioral Manifestations
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D000015	Abnormalities, Multiple
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D025063	Chromosome Disorders
D030342	Genetic Diseases, Inborn
D000096803	Imprinting Disorders
D009765	Obesity
D050177	Overweight
D044343	Overnutrition
D009748	Nutrition Disorders
D009750	Nutritional and Metabolic Diseases

Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg placebo for DCCR tablets could be taken; Placebo was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed.

The target dose by weight (kg) was as follows:

Subjects weighing 20 to < 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to < 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to < 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to < 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to < 135 took 450mg DCCR/day. Subjects randomized to the Placebo group were titrated on placebo, similar to the DCCR group.