Clinical Trials Register

Summary
EudraCT Number:	2018-004216-22
Sponsor's Protocol Code Number:	C602
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-06-27
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2018-004216-22

A.3

Full title of the trial

An Open-Label, Long-Term Safety and Efficacy Evaluation of Diazoxide Choline Controlled-Release Tablet in Patients with Prader-Willi Syndrome

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to determine the safety of the study drug Diazoxide Choline Controlled-Release Tablet after being given for a long time to patients with the genetic disorder Prader-Willi Syndrome.

A.4.1

Sponsor's protocol code number

C602

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Soleno Therapeutics UK Ltd.
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Soleno Therapeutics, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Soleno Therapeutics UK Limited
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Garden Cottage, Badgemore Park
B.5.3.2	Town/ city	Henley on Thames, Oxon
B.5.3.3	Post code	RG9 4NR
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441628876432
B.5.6	E-mail	C602ProjectManager@soleno.life

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/17/1941
D.3 Description of the IMP
D.3.1	Product name	diazoxide choline
D.3.2	Product code	DCCR
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Diazoxide choline
D.3.9.1	CAS number	1098065-76-9
D.3.9.2	Current sponsor code	DCCR
D.3.9.3	Other descriptive name	DIAZOXIDE CHOLINE
D.3.9.4	EV Substance Code	SUB192374
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	25 to 150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hyperphagia associated with Prader-Willi Syndrome (PWS)

E.1.1.1

Medical condition in easily understood language

Genetic disorder (Prader-Willi) causing a weakness in shape and form of muscle, poor growth, delayed development in infants & increased appetite and food-related behaviour later on.

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10020710
E.1.2	Term	Hyperphagia
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the long-term safety of diazoxide choline controlled-release (DCCR) tablets in PWS patients.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to evaluate changes in hyperphagia, body fat mass, lean body mass, lean body mass/body fat mass ratio, cardiometabolic markers, insulin resistance (HOMA-IR), Clinical Global Impression of Improvement (CGI-I), and Caregiver Global Impression of Change (GI-C) associated with DCCR treatment of PWS patients. Additional objectives of this study include the evaluation of changes in percent body fat, weight, body mass index (BMI), waist circumference, lipid parameters, patient’s health-related quality of life, caregiver burden, cardiometabolic markers, Clinical Global Impression of Severity (CGI-S), Caregiver Global Impression of Severity, Caregiver Global Impression of Change (GI-C) of Food-Related Behaviours for Hyperphagia Questionnaire for Clinical Trials (HQ-CT), Caregiver GI-C of Overall Behaviour, Environmental controls on food access, Developmental Behaviour Checklist 2-Parent (DBC2-P), PWS behaviours with DCCR treatment of PWS patients.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The following are considered to be the Principal Inclusion Criteria for Study C602:
1) Successful completion of clinical study C601;
2) Provide voluntary, written informed consent (parent(s) / legal guardian(s) of subject); provide voluntary, written assent (subject, as appropriate);
3) Primary caregiver must be able to communicate with Investigator and study site personnel as well as read and complete the study-required questionnaires.

E.4

Principal exclusion criteria

The following are considered to be the Principal Exclusion Criteria for Study C602. Participants cannot enter C602 if not completed C601:
1) 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 http://medicine.iupui.edu/CLINPHARM/ddis/clinical-table, Flockhart Table);
• Medications known to prolong the QTc interval (Refer to QT Drugs List on https://crediblemeds.org/healthcare-providers/), except citalopram and escitalopram;
• 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 safety endpoints;
• Use of any investigational drugs or devices;
2) Positive urine pregnancy test (in females of childbearing potential);
3) Females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 90 days after study participation;
4) 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);
5) New history in a first degree relative since the subject enrolled in clinical study C601 or a change in the subject’s physical examination that, in the opinion of the investigator, significantly increases the subject’s risk for thromboembolic event (e.g., venous thrombosis, pulmonary embolism, etc.).

E.5 End points

E.5.1

Primary end point(s)

The following safety & efficacy endpoints will be evaluated in this study.
Safety:
• Adverse events
• Vital signs
• Electrocardiogram (ECG)
• Peripheral edema assessment
• Thromboembolic event assessment
• Hirsutism / hypertrichosis assessment
• Clinical laboratory assessments:
• Fasting plasma glucose
− Fasting plasma insulin
− HbA1c
− Chemistry panel
− Liver function tests
− Hematology panel
− Prothrombin time, (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR)
− Insulin resistance (HOMA-IR)
− Urinalysis
• Insulin-like Growth Factor-1 (IGF-1)
• Columbia Suicide Severity Rating Scale (C-SSRS, caregiver response)
• PWS Behaviours associated with suicide risk.

Efficacy Endpoints:
• Hyperphagia change from Baseline (using HQ-CT)
• Body fat mass (DXA) change from Baseline
• Lean body mass (DXA) change from Baseline
• Lean body mass / fat mass ratio (DXA) change from Baseline
• Change in cardiometabolic markers (high-sensitivity C-reactive protein, adiponectin, ghrelin and leptin) from Baseline
• Change in insulin resistance (HOMA-IR) from Baseline
• Clinical Global Impression of Improvement
• Caregiver Global Impression of Change.
All efficacy and exploratory endpoints may be evaluated from Baseline to Visits 3, 5, 6, 15, 19 and/or 23.

E.5.1.1

Timepoint(s) of evaluation of this end point

End of study

E.5.2

Secondary end point(s)

For all exploratory endpoints, Baseline 1 = clinical study C601 Visit 2 and Baseline 2 = clinical study C601 Visit 7 / clinical study C602 Visit 1. All exploratory endpoints will evaluate the changes or percent change from both Baseline 1 and Baseline 2.
The following exploratory endpoints will also be evaluated in this study:
• Change in percent body fat (DXA) from Baseline
• Weight change from Baseline
• BMI change from Baseline
• Waist circumference change from Baseline
• Triglyceride percent change from Baseline
• Total cholesterol percent change from Baseline
• Non-high-density lipoprotein (HDL) cholesterol percent change from Baseline
• Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol percent change from Baseline
• Change in subject’s health related Quality of Life (using EQ-5D-Y:1, Proxy Version) from Baseline
• Caregiver burden (by Zarit Burden Interview [ZBI]) change from Baseline
• Change in Clinical Global Impression of Severity from Baseline
• Change in Caregiver Global Impression of Severity from Baseline
• Change in Caregiver Global Impression of Change of Food-Related Behaviors for HQ-CT
• Change in Caregiver Global Impression of Change of Overall Behaviour
• Change in environmental controls on food access (using Food Safe Zone) from Baseline 1
• Change in the Developmental Behaviour Checklist 2 – Parent (DBC2-P) from Baseline
• Change in externalizing behaviors, aggressive problems (PWS Profile questionnaire - Aggression domain) from Baseline
• Change in anxious behaviors (PWS Profile questionnaire – Anxiety domain) from Baseline
• Change in compulsivity (PWS Profile questionnaire – Compulsivity domain) from Baseline
• Change in irritability (PWS Profile questionnaire – Rigidity, Irritability domain) from Baseline
• Change in depressive behaviors (PWS Profile questionnaire – Depression domain) from Baseline
• Change in disordered thinking (PWS Profile questionnaire – Disordered Thinking domain) from Baseline
• Change in individual infrequent behaviours of high clinical significance (PWS Profile questionnaire) from Baseline
All exploratory endpoints may be evaluated from Baseline to Visits 3, 5, 6, 15, 19 and/or 23.

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 15

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of trial is the completion of the analyses of the final data. Data are considered final when all queries related to the data are resolved, the data are clean, and the database has been locked.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Intellectual disability is common in PWS. Patient assent and parent/guardian consent will be obtained. Sexual maturity is usually not achieved without aid and puberty is rarely completed. Where pregnancy is possible, real contraception is required.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

105

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Depending on the safety and efficacy profile of DCCR in this study and in study C601, a further long-term safety study may follow this study. Alternatively, the IMP may be made available to subjects on a named patient basis or they may continue on their normal pre-study treatment for the condition.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Clinical Research Network North Thames
G.4.3.4	Network Country	United Kingdom

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-07-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-25

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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