Clinical Trials Register

Summary
EudraCT Number:	2011-005903-34
Sponsor's Protocol Code Number:	KKSMUW2011-09
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-29
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

Austria - BASG

A.2

EudraCT number

2011-005903-34

A.3

Full title of the trial

Phase II, single centre, double blinded, cross-over dose confirmation study using two morphine-naloxone i.v. solutions

Dosisfindungsstudie mit 2 Morphin-Naloxon Lösungen zur intravenösen Verabreichung.

A.3.1

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

Development of a morphine-naloxone combination.

Entwicklung einer Kombination von Morphin und Naloxon.

A.4.1

Sponsor's protocol code number

KKSMUW2011-09

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	G. L. Pharma GmbH
B.1.3.4	Country	Austria
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	G. L. Pharma GmbH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	G. L. Pharma GmbH
B.5.2	Functional name of contact point	G. L. Pharma GmbH
B.5.3	Address:
B.5.3.1	Street Address	Schlossplatz 1
B.5.3.2	Town/ city	Lannach
B.5.3.3	Post code	8502
B.5.3.4	Country	Austria
B.5.4	Telephone number	004313136-82-577-0
B.5.5	Fax number	004313136-81 563
B.5.6	E-mail	office@gl-pharma.at

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	No
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	Morphine- Naloxone
D.3.2	Product code	Morphine-Naloxone
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 bolus use (Noncurrent) Auricular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	51481-60-8
D.3.9.3	Other descriptive name	NALOXONE HYDROCHLORIDE DIHYDRATE
D.3.9.4	EV Substance Code	SUB12168MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	0,75
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	6055-06-7
D.3.9.3	Other descriptive name	MORPHINE HYDROCHLORIDE TRIHYDRATE
D.3.9.4	EV Substance Code	SUB27294
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	75
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	No
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	Morphine Mono
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 bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	6055-06-7
D.3.9.3	Other descriptive name	MORPHINE HYDROCHLORIDE TRIHYDRATE
D.3.9.4	EV Substance Code	SUB27294
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	75
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

Treatment of opioid dependence

Behandlung von Opioidabhängigkeit

E.1.1.1

Medical condition in easily understood language

Treatment of opioid dependence

Behandlung von Opioidabhängigkeit

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Behaviours [F01]

MedDRA Classification

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 appropriate ratio of morphine and naloxone to suppress the pleasurable effects of intravenous morphine and precipitate withdrawal reactions.

E.2.2

Secondary objectives of the trial

Assessment of individual physiological variables and symptoms and vital signs during study drug administration at various time points.
Assessment of safety including adverse events, clinical laboratory results and vital signs.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male, over the age of 18 years
- meet DSM-IV criteria for the diagnosis of opioid dependence currently undergoing morphine mainteinance treatment,
- with a history of regular opioid abuse,
- under opioid maintenance treatment for opioid abuse with morphine (occasionally injecting heroin) with a constant dose for ≥ 1 month,
- in good health and have venous access sufficient for i.v. drug administration
- with assessed normal QTc time (Bazzett corrected <500ms),
- negative urine test (except for THC- tetrahydrocannabinol, “marijuana” and opioids)
- agree to be admitted to the inpatient research unit for a minimum of 7 days, and be able to complete all protocol-specified assessments,
- signed written informed consent.

Einschlusskriterien:
- Männlich, über 18 Jahre.
- Opioidabhängigkeit entsprechend DSM-IV, unter aktueller Substitutionstherapie mit Morphin.
bekannter, regelmäßiger Opioid Mißbrauch.
- Substitutionstherapie für Drogenabhängige mit Morphin (gelegentlicher Heroinkonsum), konstante Dosierung für ≥ 1 Monat.
- im guten Gesundheitszustand und ausreichenden venösen Zugang für i.v. Verabreichungen.
- normale QTc Zeit.
- neg. Drogenharntest (Ausnahme: THC , Marijuana und Opioide).
- Patienteneinwilligung 7 Tage stationär aufgenommen zu werden und sich allen protokollspezifischen Untersuchungen zu unterziehen.
- Unterzeichnete Einwilligungserklärung.

E.4

Principal exclusion criteria

- with clinically significant somatic illnesses (except stable chronic hepatitis),
- with acute psychotic illnesses, i.e. known schizophrenia, major depression with suicidal intent,
- with opioid maintenance treatment with morphine at variable doses or for a period of < 1 month,
- with daily alcohol consumption of > 100 g during the last 4 weeks,
- with cocaine dependence,
- showing contraindications to morphine (known hypersensitivity to opioids, restricted respiratory function, serious impairment of liver and/or kidney function, inter alia),
- uncooperative patients, unwilling to follow instructions by the Investigator,
- patients scheduled for any major surgery or intervention, which would fall within the study period,
- patients who have participated in another clinical research study involving a new chemical entity within 3 months of study entry,
- patients who, in the opinion of the Investigator, are unsuitable to participate in the study for any other reason not mentioned in the inclusion and exclusion criteria,
- with imprisonment or under criminal prosecution for the following
4 week-period,
- with incapacitation and court appointment.
- with documented (ultrasound or right heart catheter) heart failure (NYHA >II)
- with documented (ECG) history of cardiac arrhythmia

Ausschlusskriterien:
- klinisch signifikante somatische Erkrankung (Ausnahme: stabile chronische Hepatitis).
- akute psychotischer Erkrankung (z. B Schizophrenie, ..).
- unter Substitutionstherapie für Drogenabhängige mit Morphin , variabler Dosierung für < 1 Monat.
- mit einem täglichen Alkoholkonsum von > 100g während der letzten 4 Wochen.
- Kokainabhängigkeit.
- Kontraindikationen gegenüber Morphin (Hypersensitivität, eingeschränkte respiratorische Funktion, …).
- Mangelnde Kooperationsbereitschaft mit dem Studienteam
- Patienten mit einem geplanten größeren Eingriff bzw. Intervention während der Studiendauer
- Behandlung mit einer nicht zugelassenen Medikation innerhalb von 3 Monaten vor Studienbeginn
- Patienten, die aus der Sicht des Prüfers aufgrund von weiteren Gründen (welche nicht in den Aus- und Einschlusskriterien enthalten sind) nicht an dieser Studie teilnehmen sollten
- Freiheitsstrafe oder Strafverfolgung für die nächsten 4 Wochen
- Entmündigung oder Strafverfahren

E.5 End points

E.5.1

Primary end point(s)

Signs and symptoms of opioid-withdrawal at various time points.

Messung der Entzugssymtomatik

E.5.1.1

Timepoint(s) of evaluation of this end point

0 to 120 minutes

0 bis 120 Minuten

E.5.2

Secondary end point(s)

- Pupil diameter and vital signs at various time points.

Pupillendurchmesser und Vitalparameter zu verschiedenen Zeitpunkten.

E.5.2.1

Timepoint(s) of evaluation of this end point

0 to 120 minutes

0 bis 120 Minuten

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Morphine Mono

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)

Yes

F.1.3.1

Number of subjects for this age range:

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)

Standard of care (Opioid maintainance therapy)

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Med. Univ. Wien, Klinik für Psychiatrie
G.4.3.4	Network Country	Austria

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-05-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-08-02

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