Clinical Trials Register

Summary
EudraCT Number:	2015-003542-68
Sponsor's Protocol Code Number:
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:	2015-11-04
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

2015-003542-68

A.3

Full title of the trial

The effect of single-dose losartan on the basic effects of cognitive-behaviour therapy for panic disorder - a randomized double blind placebo-controlled trial

A.3.1

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

Cognitive-behaviour therapy and losartan

A.3.2

Name or abbreviated title of the trial where available

Cognitive-behaviour therapy and losartan

A.4.1

Sponsor's protocol code number

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 of Oxford
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	MQ: Transforming Mental Health
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 of Oxford
B.5.2	Functional name of contact point	Dr Andrea Reinecke
B.5.3	Address:
B.5.3.1	Street Address	Department of Psychiatry
B.5.3.2	Town/ city	Oxford
B.5.3.3	Post code	OX37JX
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01865226471
B.5.6	E-mail	andrea.reinecke@psych.ox.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.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Limited
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	losartan
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	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	losartan
D.3.9.1	CAS number	114798-26-4
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	50
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	Capsule
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

DSM panic disorder

E.1.1.1

Medical condition in easily understood language

Panic disorder is a severe form of anxiety that is characterised by the occurence of intense panic attacks, without an apparent external reason.

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Psychological processes [F02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	HLT
E.1.2	Classification code	10068300
E.1.2	Term	Panic attacks and disorders
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

To investigate whether the combination of a single-session of cognitive-behaviour therapy (CBT) with the antihypertensive drug (compared to placebo) leads to greater reduction in threat bias on the day after treatment.

E.2.2

Secondary objectives of the trial

*To investigate whether such an increased change in threat bias is underpinned by stronger alterations in responsivity in the fear circuit of the brain on the day after treatment;

*To investigate whether CBT plus losartan (versus placebo) leads to greater symptom improvement on the day after treatment and at follow-ups;

*To investigate whether CBT plus losartan (versus placebo) leads to greater stress resistance on the day after treatment and at follow-ups

*To investigate whether threat bias measured before treatment can predict treatment success with placebo versus losartan

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

*Participant is willing and able to give informed consent for participation in the study and to comply with all study requirements
*Male or Female, aged 18 years or above
*Diagnosed with DSM-IV panic disorder
*At least moderate avoidance of agoraphobic situations (”yes” response to at least 3 situations listed under “(2) Avoidance – Do you avoid or feel very uncomfortable in …” in the Structured Panic Assessment Interview (Clark, 1989)

E.4

Principal exclusion criteria

*Female participant who is pregnant or breast-feeding
*CNS-active medication during the last 6 weeks
*Current blood pressure or other heart medication (especially aliskiren or beta blockers)
*Intravascular fluid depletion
*Impaired liver or kidney function
*Lifetime history of epilepsy or other neurological disease, systemic infection, or clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, metabolic, endocrine or pulmonary disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study.
*Lifetime history of psychosis, bipolar disorder, alcohol, medication or drug abuse or dependence; current primary depressive disorder
*Insufficient English skills
*Participated in another study involving certain medication during the last 6 weeks
*Exposure-based psychological treatment for panic disorder and agoraphobia during the last 3 months
*Patient not able to refrain from benzodiazepines 48hrs before treatment and testing sessions

Participants with MRI contraindications (e.g. pacemaker, metal implant, left-handedness) will be included in the study but will not undergo the MRI scan study component.

E.5 End points

E.5.1

Primary end point(s)

Threat bias on the day after treatment (reaction time scores derived from computerised behavioural reaction tasks)

E.5.1.1

Timepoint(s) of evaluation of this end point

day after treatment (visit 3)

E.5.2

Secondary end point(s)

*Responsivity in the fear circuit of the brain (fMRI);
*Self-report (BDI, STAIT. STAIS, ACQ, BSQ, MI, PAS) and clinician-rated (PDSSC, CGI) symptom questionnaire scores;
*Anxiety ratings during stress test (VAS);
*Threat bias measured with EEG

E.5.2.1

Timepoint(s) of evaluation of this end point

*fMRI: day after treatment (visit 3)
*symptom questionnaire scores: before treatment, day after treatment, 1- and 6-month follow-up (visits 2, 3, 4, 5)
*stress test: before treatment, day after treatment, 1- and 6-month follow-up (visits 2, 3, 4, 5)
*EEG: before teratment (visit 2)

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

Yes

E.6.6

Pharmacokinetic

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

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 date is the date of the last follow-up appointment of the last participant.

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