Clinical Trials Register

Summary
EudraCT Number:	2012-005701-43
Sponsor's Protocol Code Number:	PROP-001-CP3
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-06-01
Trial results	View 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

France - ANSM

A.2

EudraCT number

2012-005701-43

A.3

Full title of the trial

Therapeutic Equivalence Study of Propofol Using Target-Controlled Infusion of Propofol 2% (20 mg/mL) MCT Fresenius Compared with Diprivan® 20 mg/mL (AstraZeneca) in Patients Undergoing Elective Surgery

A.3.1

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

Therapeutic Equivalence Study of Propofol Compared with Diprivan® in Patients Undergoing Elective Surgery

A.4.1

Sponsor's protocol code number

PROP-001-CP3

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	Fresenius Kabi Deutschland GmbH
B.1.3.4	Country	Germany
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	Fresenius Kabi Deutschland GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fresenius Kabi Deutschland GmbH
B.5.2	Functional name of contact point	Medical & Clinical Affairs
B.5.3	Address:
B.5.3.1	Street Address	Borkenberg 14
B.5.3.2	Town/ city	Oberursel
B.5.3.3	Post code	61440
B.5.3.4	Country	Germany
B.5.4	Telephone number	00496172686-7363
B.5.5	Fax number	00496172686-7267
B.5.6	E-mail	jasmin.tajeri-foman@fresenius-kabi.com

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	Propofol 2% (20 mg/mL)
D.2.1.1.2	Name of the Marketing Authorisation holder	Fresenius Kabi Deutschland GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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 2% (20 mg/mL) MCT Fresenius
D.3.4	Pharmaceutical form	Emulsion 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	Propofol
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	20
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	Diprivan® 20 mg/mL
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Emulsion 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	Propofol
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/l milligram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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

Elective minor Surgery

E.1.1.1

Medical condition in easily understood language

Elective minor Surgery

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10042609
E.1.2	Term	Surgery
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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 evaluate the therapeutic equivalence, based on pharmacodynamic parameters, of Propofol 2% (20 mg/mL) MCT Fresenius and Diprivan® 20 mg/mL (AstraZeneca) administered by target-controlled infusion (TCI)

E.2.2

Secondary objectives of the trial

To evaluate the safety, tolerability, and pharmacokinetics (PK) of Propofol 2% (20 mg/mL) MCT Fresenius compared to Diprivan® 20 mg/mL (AstraZeneca)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female subjects ≥18 years and <65 years old
2. Able to understand and give signed and dated written informed consent
3. Body mass index (BMI) ≥20 and ≤30 kg/m2 at screening
4. ASA physical status 1 or 2
5. Undergoing elective, minor orthopaedic, vascular, urological, or gynaecological surgery

E.4

Principal exclusion criteria

1. The following planned procedures are to be excluded:
- Day surgery
- Emergency surgery
- Total hip or total knee replacement
- Requiring opening of the great cavities of the body (cranium, thorax, peritoneum, or pelvis)
- With routine risk, even if low, of haemorrhage severe enough to require administration or colloid or blood products
- With routine risk, even if low, of death during or soon after the procedure
- Vascular surgery involving the aorta, venae cavae, iliac arteries, or femoral arteries
2. Intended administration of IV medications through a central venous catheter
3. Administration of general anaesthesia or propofol within the 7 days prior to randomisation
4. History of hypersensitivity to propofol, eggs, Soya, peanuts, or any other constituent of the study drugs
5. ASA physical status ≥3
6. History of major anaesthesia complications
7. History of difficult airway management
8. History of difficult venous access
9. Myocardial infarction within 6 months of randomisation or a cardiac reperfusion procedure within 6 weeks of randomisation
10. Significant respiratory, cardiovascular, liver or renal disease as assessed by Investigator
11. Active systemic infection (localised infection related to surgical procedure is allowable as long as there is no indication of systemic involvement)
12. History of psychiatric disorder, including use of sedatives or antidepressants for any reason, within 6 months prior to randomisation
13. Alcohol or other substance abuse within 2 years prior to randomisation, as well as for the duration of the study
14. Use of medication that could reduce the subject’s respiratory and cardiac output

E.5 End points

E.5.1

Primary end point(s)

time to LOER

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1

E.5.2

Secondary end point(s)

Pharmacodynamic (PD) outcomes
- Predicted effect site propofol concentrations at time of LOER
- Time to BIS 50
- Predicted effect site propofol concentrations at time of BIS 50

Pharmacokinetic (PK) outcomes
- Plasma propofol concentration: pre-infusion, during infusion, and after infusion
- Mean estimated plasma propofol concentration at time of LOER
- Mean estimated plasma propofol concentration at time of BIS 50
- Mean estimated plasma propofol concentration at time of eye opening

Tolerability
- Pain at infusion site for anaesthesia induction

Safety outcomes
-Maximum percent change in mean arterial pressure (MAP) from baseline at time to LOER
- Maximum percent change in heart rate from baseline at time to LOER
- Mean intra-operative blood pressure
- Mean intra-operative heart rate
- 12-Lead ECG
- Time to eye opening
- Total propofol dose
- Total remifentanil dose
- Total ephedrine dose
- Total phenylephrine dose
- Post-operative nausea and vomiting
- Plasma lactate level at stop of the study drug infusion
- Day 1 adverse events (AEs)
- Days 7 to 14 AEs

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 1+ Day 7 to 14

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

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Theurapeutic equivalence, tolerability

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

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

Yes

E.8.1.7.1

Other trial design description

Theurapeutic equivalence

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

Diprivan® 20 mg/mL

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

last visit of the last patient undergoing the study to be conducted in October 2013

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.1.1.1

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

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2015-06-01.

Yes

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

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)

Standard of care

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

2013-04-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-02-13

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