Clinical Trials Register

Summary
EudraCT Number:	2012-005812-24
Sponsor's Protocol Code Number:	MalinJonssonFagerlund10
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-01
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

Sweden - MPA

A.2

EudraCT number

2012-005812-24

A.3

Full title of the trial

Acute ventilatory response to hypoxia during sedation with dexmedetomidine compared to propofol in healthy volunteers.

A.3.1

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

Effects of the breathing response during reduced oxygen tension and simultaneous infusion of dexmedetomidine compared to propofol, two sedating agents.

A.4.1

Sponsor's protocol code number

MalinJonssonFagerlund10

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	Karolinska University Hospital
B.1.3.4	Country	Sweden
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	Karolinska Institutet and Karolinska University Hospital, Solna
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Karolinska University Hospital
B.5.2	Functional name of contact point	Clinical Research Unit
B.5.3	Address:
B.5.3.1	Street Address	Dept of Anesthesia and Intensive Care, Karolinska University Hospital, Solna
B.5.3.2	Town/ city	Stockholm
B.5.3.3	Post code	17176
B.5.3.4	Country	Sweden
B.5.4	Telephone number	460851772066

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	Dexdor
D.2.1.1.2	Name of the Marketing Authorisation holder	Orion Corporation
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEXMEDETOMIDINE
D.3.9.1	CAS number	113775-47-6
D.3.9.3	Other descriptive name	dexmedetomidine
D.3.9.4	EV Substance Code	SUB07037MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Propofol-Lipuro
D.2.1.1.2	Name of the Marketing Authorisation holder	B. Braun Melsungen AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Propofol-Lipuro
D.3.4	Pharmaceutical form	Emulsion for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	propofol
D.3.9.1	CAS number	2078-54-8
D.3.9.3	Other descriptive name	PROPOFOL
D.3.9.4	EV Substance Code	SUB10116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10 to 10
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Healthy volunteers and the acute hypoxic ventilatory response during sedation with dexmedetomidine compared to propofol.

Friska försökspersoner och effekt på det akuta hypoxiska ventilatoriska svaret vid sedering med dexmedetomidin jämfört med propofol.

E.1.1.1

Medical condition in easily understood language

Healthy volunteers and the breathing response to inspiration of a low fraction of oxygen during sedation with dexmedetomidine compared to propofol.

Friska försökspersoner och andningssvar vid låg syrgashalt under sedering med dexmedetomidin jämfört med propofol, två olika lugnande läkemedel.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10068084
E.1.2	Term	Anesthesia procedure
E.1.2	System Organ Class	100000004865

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10062825
E.1.2	Term	Monitored anaesthesia care sedation
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. Does dexmedetomidine affect the acute hypoxic ventilatory response in healthy volunteers? 2. Is the acute hypoxic ventilatory response in healthy volunteers less affected with dexmedetomidine than propofol at the same level of sedation?

1. Påverkar dexmedetomidin det hypoxiska ventilatoriska svaret hos friska försökspersoner? 2. Påverkar dexmedetomidin det hypoxiska ventilatoriska svaret mindre än propofol vid motsvarande sederingsnivå hos friska försökspersoner?

E.2.2

Secondary objectives of the trial

1. Does dexmedetomidine affect the acute hypercapnic ventilatory response in healthy volunteers?
2. Is the acute hypercapnic ventilatory response in healthy volunteers less affected dexmedetomidine than propofol at the same level of sedation?
3. Are there signs of an obstructed airway during sedation with dexmedetomidine or propofol?
4. How does the plasma concentration of dexmedetomidine and propofol correlate to the level of sedation according to Observer´s Assessment of Alertness/Sedation Scale (OAA/S) and Richmond Agitation Sedation Score (RASS)?
5. How does the level of sedation according to (OAA/S) correlate to (RASS) during dexmedetomidine and propofol infusion?
6. Does the level of sedation according to OAA/S and RASS correlate to BIS during sedation with dexmedetomidine and propofol?

1. Påverkar dexmedetomidin hyperkapnisk ventilatorisk respons (HCVR) hos friska försökspersoner?
2. Påverkar dexmedetomidin hyperkapnisk ventilatorisk respons (HCVR) mindre än propofol vid motsvarande sederingsnivå?
3. Ser man tecken till obstruerad övre luftväg vid sedering med dexmedetomidin eller propofol?
4. Hur relaterar plasmakoncentration till grad av sedering med dexmedetomidin och propofol mätt med Observer´s Assessment of Alertness/Sedation Scale (OAA/S) och Richmond Agitation Sedation Score (RASS)?
5. Hur väl korrelerar OAA/S med RASS vid sedering med dexmedetomedin och propofol?
6. Hur väl korrelerar OAA/S och RASS med bispektral index (BIS) vid sedering med dexmedetomedin och propofol?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Healthy male volunteers 18-40 years of age. No allergy or medication. Non-smokers, non-tobacco user. Normal weight, that is BMI<26.

Helt friska män 18-40 år utan allergier eller medicinering. Icke-rökare/snusare. Normal vikt, dvs BMI<26.

E.4

Principal exclusion criteria

Those who do not fulfill the inclusion criteria. Snoring during sleep. A beard or anatomy that unables the breathing mask to fit tightly.

De som inte uppfyller inklusions-kriterierna. Känd snarkning. Skägg som omöjliggör att andningsmasken sluter tätt.

E.5 End points

E.5.1

Primary end point(s)

Hypoxic ventilatory response. That is the change of minute ventilation (VE) divided by the change in saturation (SpO2).

Hypoxiskt ventilatoriskt svar, dvs den förändrade minutvolymen (VE) dividerat med förändrad saturation (SpO2).

E.5.1.1

Timepoint(s) of evaluation of this end point

When the second breathing test is done and the acute hypoxic ventilatory response has been measured during infusion of dexmedetomidine to achieve a moderate level of sedation according to Observer´s Assessment of Alertness/Sedation Scale (OAA/S).

När det andra andningstestet har genomförts i studien och hypoxisk ventilatorisk respons har kontrollerats under infusion dexmedetomidin till moderat sederingsnivå enligt Observer´s Assessment of Alertness/Sedation Scale (OAA/S).

E.5.2

Secondary end point(s)

Hypercapnic ventilatory respons. Respiratory rate. Tidal volume. Airway flow. Thoracic and abdominal impedance. Oxygen saturation. Level of sedation according to Observer´s Assessment of Alertness/Sedation Scale (OAA/S), Richmond Agitation Sedation Score (RASS) and bispectral index (BIS). Plasma concentration of dexmedetomidine and propofol.

Hyperkapnisk ventilatorisk respons. Andningsfrekvens. Tidalvolymer. Andningsflöde. Buk och thoraximpedans. Syrgassaturation. Sederingsnivå skattad enligt Observer´s Assessment of Alertness/Sedation Scale (OAA/S), Richmond Agitation Sedation Score (RASS) och bispektral index (BIS). Plasma koncentration av dexmedetomidin och propofol.

E.5.2.1

Timepoint(s) of evaluation of this end point

When the second breathing test is done and the acute hypercapnic ventilatory response has been measured during infusion of dexmedetomidine to achieve a moderate level of sedation according to Observer´s Assessment of Alertness/Sedation Scale (OAA/S).

När det andra andningstestet har genomförts i studien och hyperkapnisk ventilatorisk respons har kontrollerats under infusion dexmedetomidin till moderat sederingsnivå enligt Observer´s Assessment of Alertness/Sedation Scale (OAA/S).

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

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

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

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Försökspersonerna är sina egna kontroller. Försöket börjar med en undersökning utan läkemedel.

The volunteers are their own comparator. The investigation will also be done without the drug.

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

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

LVLS

Studien är slutförd när samtliga försökspersoner har genomfört andningstest efter utsatt infusion dexmedetomidin eller propofol, dvs efter undersökningsdag nummer två.

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

Yes

F.3.2

Patients

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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

Inga

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

2013-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-09-16

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