Clinical Trials Register

Summary
EudraCT Number:	2011-003648-31
Sponsor's Protocol Code Number:	PKPDHM-001
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-08-18
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

Germany - BfArM

A.2

EudraCT number

2011-003648-31

A.3

Full title of the trial

Pharmacokinetic-pharmacodynamic modeling of the postoperative pain sensation during patient-controlled analgesia with target-controlled infusion of Hydromorphone, taking into account the interaction with intraoperatively administered Sufentanil for elective cardiac surgery

Pharmakokinetisch-pharmakodynamische Modellbildung der postoperativen Schmerzempfindung während patientengesteuerter Analgesie mit „Target-controlled Infusion“ von Hydromorphon unter Berücksichtigung der Interaktion mit intraoperativ verabreichtem Sufentanil bei elektiven kardiochirurgischen Eingriffen

A.3.1

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

Generation of a model for the adaption of the postoperative pain therapy with the strong analgesic, hydromorphone, after planned open heart surgery, during which the strong analgesic, sufentanil, was used

Erstellung eines Modells zur Anpassung der postoperativen Schmerzbehandlung mit dem starken Schmerzmittel Hydromorphon nach geplanten Operationen am offenen Herz, bei denen das starke Schmerzmittel Sufentanil eingesetzt wurde

A.3.2

Name or abbreviated title of the trial where available

PkPd Hydromorphon-Sufentanil

A.4.1

Sponsor's protocol code number

PKPDHM-001

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	Universitätsklinikum Erlangen
B.1.3.4	Country	Germany
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	Bundesministerium für Bildung und Forschung
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	Universitätsklinikum Erlangen
B.5.2	Functional name of contact point	Anästhesiologische Klinik
B.5.3	Address:
B.5.3.1	Street Address	Krankenhausstrasse 12
B.5.3.2	Town/ city	Erlangen
B.5.3.3	Post code	91052
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4991318542363
B.5.5	Fax number	+4991318539161
B.5.6	E-mail	christian.jeleazcov@kfa.imed.uk-erlangen.de

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	Sufenta 50µg/ml Injektionslösung
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Solution for injection
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	SUFENTANIL CITRATE
D.3.9.1	CAS number	60561-17-3
D.3.9.4	EV Substance Code	SUB04616MIG
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	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.IMP: 2
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	Palladon Injekt 10mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Mundipharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Solution for injection
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	HYDROMORPHONE HYDROCHLORIDE
D.3.9.1	CAS number	71-68-1
D.3.9.4	EV Substance Code	SUB02573MIG
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
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

Pain therapy after elective cardiac surgery

Schmerztherapie nach elektiven kardiochirurgischen Eingriffen

E.1.1.1

Medical condition in easily understood language

Pain treatment after planned open heart surgery

Schmerzbehandlung nach geplanten Operationen am offenen Herz

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	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10036236
E.1.2	Term	Postoperative pain relief
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

Pharmacokinetic-pharmacodynamic modeling for the interaction of sufentanil (administered during surgery via target-controlled infusion) and hydromorphone (administered after surgery as patient-controlled analgesia via target-controlled infusion) in the early postoperative period

Pharmakokinetisch-pharmakodynamische Modellbildung für die Interaktion von intraoperativ verabreichtem Sufentanil (mittels Target-controlled Infusion) und postoperativ appliziertem Hydromorphon (als Patienten-kontrollierte Analgesie mittels Target-controlled Infusion) in der frühen postoperativen Phase

E.2.2

Secondary objectives of the trial

• Description and comparison of antinociception caused by sufentanil and hydromorphone in the early postoperative period through indicators assessed in both treatment arms
• Description and comparison of safety and tolerability of postoperative pain treatment with hydromorphone TCI, TCI-PCA and PCA after intraoperative sufentanil TCI in both treatment arms
• Identification of the minimal hydromorphone target plasma concentration appropriate for postoperative pain treatment

• Beschreibung und Vergleich der durch Sufentanil und Hydromorphon hervorgerufenen Antinociception in der frühen postoperativen Phase durch Erfassung von Indikatoren in den beiden Behandlungsgruppen
• Beschreibung und Vergleich der Sicherheit und Verträglichkeit der postoperativen Schmerztherapie unter TCI, TCI-PCA und konventioneller PCA mit Hydromorphon nach intraoperativer Anwendung einer Sufentanil-TCI in den beiden Behandlungsgruppen
• Bestimmung der für die postoperative Schmerztherapie geeigneten minimalen Plasmazielkonzentration von Hydromorphon

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Written informed consent
Ability to understand the nature of patient-controlled analgesia and other study-specific procedures
Elective cardiac surgery with thoracotomy and subsequent stay in the intensive care unit

Schriftliche Einverständniserklärung
Fähigkeit, das Wesen der Patienten-kontrollierten Analgesie und weiterer studienspezifischer Maßnahmen zu verstehen
Elektiver kardiochirurgischer Eingriff mit Thorakotomie und anschließendem Aufenthalt auf der Intensivstation

E.4

Principal exclusion criteria

Use of MAO inhibitors in the last 14 days
Chronic alcoholism or drug addiction in medical history
Severe obstuctive or restrictive pulmonal disorders in medical history
Severe hepatic and renal disorders in medical history
Hypothyroidism, prostate hyperplasia, pancreatitis, biliary or renal colic in medical history
ASA IV
Pregnant or nursing females

Anwendung von MAO-Hemmern in den vergangenen 14 Tagen
Dhronischer Alkoholabusus oder Drogenabhängigkeit in der Anamnese
Schwerwiegende obstruktive oder restriktive Lungenerkrankungen in der Anamnese
Schwerwiegende Leber- und Nierenfunktionsstörungen in der Anamnese
Hypothyreose, Prostatahypertrophie, Nebenniereninsuffizienz, Pankreatitis, Gallen- oder Nierenkoliken in der Anamnese
ASA IV
Schwangere und stillende Mütter

E.5 End points

E.5.1

Primary end point(s)

• Course and comparison of the course of the Numerical Rating Scale-11 scores over time between the two treatment arms
• Plasma concentrations of sufentanil and hydromorphone at predefined timepoints for both treatment arms

• Verlauf und Vergleich des Verlaufs der Numerical Rating Scale 11-Werte über den Untersuchungszeitraum in den beiden Behandlungsgruppen
• Plasmakonzentrationen von Sufentanil und Hydromorphon zu den Abnahmezeitpunkten getrennt nach Behandlungsgruppen

E.5.1.1

Timepoint(s) of evaluation of this end point

Visits 2 and 3 (Day 1 and 2/3)

Visiten 2 und 3 (Tag 1 und 2/3)

E.5.2

Secondary end point(s)

• Amount of sufentanil administered during sufentanil TCI for both treatment arm
• Amount of hydromorphone administered during hydromorphone TCI, TCI-PCA and PCA for both treatment arms
• Comparison of concentrations of sufentanil and hydromorphone at half-maximal effect EC50 between treatment arms
• Pharmacokinetics of sufentanil and hydromorphone for both treatment arms
• Frequency and incidence of AEs and SAEs in both treatment groups
• MOAA/S at predefined timepoints in both treatment arms

• Verabreichte Menge von Sufentanil während der Sufentanil-TCI getrennt nach Behandlungsgruppen
• Verabreichte Menge von Hydromorphon während der Hydromorphon-TCI, der Hydromorphon-TCI-PCA und der konventionellen Hydromorphon-PCA getrennt nach Behandlungsgruppen
• Vergleich der Konzentration zum halbmaximalen Effekt EC50 von Sufentanil und Hydromorphon zwischen den beiden Behandlungsgruppen
• Pharmakokinetische Parameter von Sufentanil und Hydromorphon getrennt nach Behandlungsgruppen.
• Anzahl und Inzidenz von AEs und SAEs getrennt nach Behandlungsgruppen
• MOAA/S zu den Bestimmungszeitpunkten getrennt nach Behandlungsgruppen

E.5.2.1

Timepoint(s) of evaluation of this end point

Visits 2, 3 and 4 (Day 1, 2/3 and 3/4)

Visiten 2, 3 und 4 (Tag 1, 2/3 und 3/4)

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

Yes

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

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

Yes

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Verschiedene Dosierungen der beiden Prüfpräparate

Different doses of the two IMPs

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 subject last visit

Letzte Visite letzter Studienteilnehmer

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)

Yes

F.1.3.1

Number of subjects for this age range:

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

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.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 after elective cardiac surgery

Standardbehandlung nach elektiven kardiochirurgischen Eingriffen

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

2011-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-09-10

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