Clinical Trials Register

Summary
EudraCT Number:	2019-003962-41
Sponsor's Protocol Code Number:	17/0909
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:	2020-02-06
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

2019-003962-41

A.3

Full title of the trial

Trial of Ondansetron as a Parkinson’s HAllucinations Treatment

A.3.1

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

Trial of Ondansetron as a Parkinson's HAllucinations Treatment: TOP HAT

A.3.2

Name or abbreviated title of the trial where available

TOP HAT

A.4.1

Sponsor's protocol code number

17/0909

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	University College London
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Parkinson's UK
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University College London
B.5.2	Functional name of contact point	Suzanne Reeves
B.5.3	Address:
B.5.3.1	Street Address	149 Tottenham Court Road
B.5.3.2	Town/ city	Lonodn
B.5.3.3	Post code	W1T 7NF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	07947036513
B.5.6	E-mail	suzanne.reeves@ucl.ac.uk

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	Yes
D.2.1.1.1	Trade name	Ondansetron 8 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Aurobindo Pharma - Milpharm Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ondansetron 8 mg film-coated tablets
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	Ondansetron hydrochloride dihydrate
D.3.9.1	CAS number	103639-04-9
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8
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	Film-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

Adults aged over 18 years with Parkinson's disease and visual hallucinations

E.1.1.1

Medical condition in easily understood language

Adults aged over 18 years with Parkinson's disease who are seeing things that do not exist

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10047570
E.1.2	Term	Visual hallucinations
E.1.2	System Organ Class	100000004873

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Can flexibly dosed ondansetron (across a 8-24mg daily dose range) effectively treat visual hallucinations in people with Parkinson’s, evidenced by clinically meaningful superiority over placebo at 12 weeks?

E.2.2

Secondary objectives of the trial

1) To establish whether ondansetron will reduce delusions
2) To determine whether ondansetron is safe and well-tolerated in people with Parkinson’s, in terms of side-effects and any impact on motor, cognitive and other non-motor symptoms
3) To establish whether ondansetron improves quality of life in people with Parkinson's.
4) To investigate whether treatment effects will be associated with improved object recognition
5) To determine whether ondansetron is cost effective for NHS use
6) To investigate pharmacokinetic variability and how this relates to clinical outcome

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Adults aged over 18 years
2) Meet Movement Disorder Society criteria for Parkinson’s disease
3) Score of 3 or more on the Scale for Assessment of Positive Symptoms- Hallucinations (SAPS-H) visual hallucinations item, indicating the presence of visual hallucinations at least weekly in the previous month
4) Score of 3 or more on SAPS-H global rating, indicating moderate symptom severity
5) Score of 4 or more on CGI-S, indicating moderate symptom severity
6) On a stable dose of anti-Parkinson’s medication, cholinesterase inhibitor or memantine for at least 28 days
7) Capacity to give informed consent or, if lacking, legal representative able to give consent.
8) Pre-menopausal women, and men whose partners are of child bearing potential will agree to use effective contraception (hormonal or barrier method of birth control; true abstinence) from the time consent is signed until 6 weeks after treatment discontinuation and inform the trial team if pregnancy occurs. For the purpose of clarity, true abstinence is when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence, withdrawal, spermicides only or lactational amenorrhoea method for the duration of a trial, are not acceptable methods of contraception).
9) Females of childbearing potential have a negative urine pregnancy test within 7 days prior to being registered/randomised. Participants are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
10) If treated with an antipsychotic drug at the time of enrolment, can still participate, provided the drug is stopped the day before trial medication is commenced.

E.4

Principal exclusion criteria

1) Bradycardia (<50 bpm) (rescreen if reversible). 2) Congenital long QTc syndrome or presence of clinically significant prolongation of QTc (>460 ms for men or >470 ms for women) on ECG screening. 3) Severe hepatic failure (bilirubin >50 micromole/L) 4) Prescribed apomorphine. 5) Prescribed tropisetron, granisetron, dolasetron. 6) History of hypersensitivity to ondansetron and its excipients (or those of placebo) or drugs listed in 5). 7)Clinically significant co-morbidity, which in the opinion of the PI would prevent safe participation in this study. 8) Unable or unwilling to comply with study procedures. 9) Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days.

E.5 End points

E.5.1

Primary end point(s)

Visual hallucinations, measured using the Scale for Assessment of Positive Symptoms (SAPS) Hallucinations (H) scores at 12 weeks.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline and after 2, 4, 6, 12, 18, and 24 weeks

E.5.2

Secondary end point(s)

Delusions
Global Severity (Impact) of symptoms
Non-motor symptoms
Proportion receiving quetiapine rescue medication
Health related quality of life
Parkinson’s symptoms (tremor, rigidity)
Cognition
ECG changes
Tolerability
Pharmacokinetics
Visual information processing

E.5.2.1

Timepoint(s) of evaluation of this end point

All of the following are measured at baseline and at 2,4,6,12,18,24 weeks:
Delusions
Global Severity (Impact) of symptoms
Non-motor symptomS;
Proportion receiving quetiapine rescue medication
Health related quality of life
Tolerability (adverse events)

Parkinson’s symptoms (tremor, rigidity) (baseline, 6 12 weeks)
Cognition (baseline, 12 weeks)
ECG changes (baseline, 6 weeks)
Pharmacokinetics (6, 12 weeks)
Visual information processing (baseline, 6 and 12 weeks)

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

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

Definition of the 'END OF TRIAL' is LVLS
End of the study is defined as the end of funding.

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

F.1.1