Clinical Trials Register

Summary
EudraCT Number:	2014-005452-26
Sponsor's Protocol Code Number:	SMR-2728
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-12-15
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

Norway - NOMA

A.2

EudraCT number

2014-005452-26

A.3

Full title of the trial

A randomized, placebo controlled, double-blind, double-dummy, 3-period cross-over study in adult patients with autism spectrum disorders evaluating cognitive response, eye-gaze, and heart rate variability after single-dose oxytocin 8 or 24 IU intranasal administration using the OptiNose bi-directional nose-to-brain device.

A.3.1

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

Effect of intranasal oxytocin on sosial cogitive tasks in autism spectrum disorder

A.4.1

Sponsor's protocol code number

SMR-2728

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	OptiNose AS
B.1.3.4	Country	Norway
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	OptiNose AS
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Kirkeveien 166, P.O.Box 4956, Nydalen
B.5.3.2	Town/ city	Oslo
B.5.3.3	Post code	0424
B.5.3.4	Country	Norway
B.5.6	E-mail	o.a.andreassen@medisin.uio.no

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	Syntocinon
D.2.1.1.2	Name of the Marketing Authorisation holder	Sigma Tau Industrie Farmaceutiche Riunite S.p.A
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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	Oxytocin
D.3.4	Pharmaceutical form	Nasal spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxytocin
D.3.9.1	CAS number	50-56-6
D.3.9.3	Other descriptive name	OXYTOCIN
D.3.9.4	EV Substance Code	SUB09580MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6.7
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	Yes
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	Nasal spray, solution
D.8.4	Route of administration of the placebo	Nasal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Autism spectrum disorder

E.1.1.1

Medical condition in easily understood language

Autism

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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10063844
E.1.2	Term	Autism spectrum disorder
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to identify effects of 8 or 24 IU oxytocin delivered intranasally with the OptiNose N2B device on performance on social-cognitive tasks compared to placebo in adult patients diagnosed with autism spectrum disorder (ASD)

E.2.2

Secondary objectives of the trial

• To identify effects of 8 or 24 IU oxytocin delivered intranasally with the OptiNose N2B device on physiological markers (heart rate variability, pupillometry, eye-tracking) compared to placebo
• Assess differential effects of 8IU and 24IU on the primary cognitive and physiological endpoints
• Determine and compare the plasma concentrations of oxytocin, vasopressin (AVP) and cortisol after 8 and 24 IU oxytocin delivered with OptiNose N2B devices in ASD patients
• Document safety (adverse event profile) of intranasally administered oxytocin with Optinose N2B device in ASD patients

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male subjects between the ages of 18 and 35, both inclusive, with a confirmed diagnosis of autism spectrum disorder (ASD) diagnosis.
2. Subjects must be in good general health, as determined by the investigator.  
3. Subject’s pre-study physical examination, vital signs and electrocardiogram (ECG) must not show any clinically significant abnormalities as determined by the investigator.
4. Subjects must be able to communicate well with the Investigator, to understand and comply with the requirements of the study, and to understand the oral and written patient information. 
5. Provision of a signed, written informed consent.

E.4

Principal exclusion criteria

1. Subjects showing major septal deviation or a significantly altered nasal epithelium.  
2. Subjects with evidence of previous nasal disease, surgery, and dependence on inhaled drugs.  
3. Subjects with current significant nasal congestion due to common colds.  
4. Subjects with a clinically relevant history of significant hepatic, renal, endocrine, cardiac, nervous, pulmonary, haematological or metabolic disorder.  
5. Psychiatric co-morbidity that requires intervention (e.g., psychosis spectrum disorders, suicide intent)
6. Systemic illness requiring treatment within 2 weeks prior to Study Day 1.
7. History of significant drug or alcohol abuse (as per WHO AUDIT/DUDIT criteria). Subjects with a positive screen for alcohol or drugs of abuse at screening/admission will be excluded from participation in the study.  
8. Abnormal laboratory values which is deemed clinically significant by investigator.  
9. Full scale IQ < 75 (due to the prerequisite ability to complete self report measures).  
10. Known allergic reactions or hypersensitivity to any component of the study medication in the nasal spray, such as propyl parahydroxybenzoate (E216), methyl parahydroxybenzoate (E218) and chlorobutanol hemihydrate.  
11. Participation in any (other) clinical trial with an investigational medicinal product or medical device within 3 months prior to randomisation.
12. Other unspecified reasons that, in the opinion of the investigator or the sponsor make the subject unsuitable for enrollment.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variables for this project are the social cognitive responses to the experimental task;
o Performance on the theory of mind task
o Performance on emotion sensitivity task
o Eyegaze (fixation duration on eye region, time to first eye fixation)

E.5.1.1

Timepoint(s) of evaluation of this end point

This will be evaluated after each dose administered.

E.5.2

Secondary end point(s)

o Physiological markers (heart rate variability, pupillometry)
o Performance on dot probe task
o Performance on facial morphing task
o Plasma concentrations of oxytocin, vasopressin and cortisol

E.5.2.1

Timepoint(s) of evaluation of this end point

This will be evaluated after each dose administered.

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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

Yes

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

LVLS

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.1.6

Adolescents (12-17 years)

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

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

None

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-02-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-02-17

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