Clinical Trials Register

Summary
EudraCT Number:	2011-002687-25
Sponsor's Protocol Code Number:	PHYSCA-1
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:	2011-10-06
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2011-002687-25

A.3

Full title of the trial

Pharmacokinetics of Hydrocortisone after Subcutaneous Administration Compared with Intramuscular Injection in Chronic Adrenal Insufficiency
(PHYSCA-Trial)

Pharmakokinetik der subkutanen Hydrocortisonapplikation im Vergleich zur intramuskulären Gabe bei chronisch Nebenniereninsuffizienten Patienten (PHYSCA- Studie)

A.3.1

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

Evaluation of the time to cortisol levels required in critical illness (>1000 nmol/l) and safety of hydrocortisone, after subcutaneous injection in patients with chronic primary adrenal insufficiency
(Comparison s.c. vs. i.m.)

Untersuchung der Zeit bis zum Erreichen relevanter Wirkspiegel (>1000 nmol/l) und der Sicherheit der subkutanen Hydocortisongabe, im Vergleich zur Gabe in den Muskel, bei Patienten mit einer chronischen Nebenniereninsuffizienz

A.3.2

Name or abbreviated title of the trial where available

PHYSCA- Trial

PHYSCA- Studie

A.4.1

Sponsor's protocol code number

PHYSCA-1

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	University Hospital of Wuerzburg
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	University Hospital Wuerzburg
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	Dept. of Endocrinology, Dept. of Medicine I, University Hospital Wuerzburg
B.5.2	Functional name of contact point	PD Dr. med. Stefanie Hahner
B.5.3	Address:
B.5.3.1	Street Address	Oberduerrbacher Str. 6
B.5.3.2	Town/ city	Wuerzburg
B.5.3.3	Post code	97080
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4993120139937
B.5.5	Fax number	+49931201639200
B.5.6	E-mail	hahner_s@medizin.uni-wuerzburg.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	Hydrocortison 100 mg (Pfizer®) in 2 ml solvent
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
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	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Hydrocortisone
D.3.9.1	CAS number	8000042-97-9
D.3.9.3	Other descriptive name	HYDROCORTISONE HYDROGEN SUCCINATE
D.3.9.4	EV Substance Code	SUB14133MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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.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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Adrenal insufficiency
under chronic glucocorticoid replacement

Nebenniereninsuffizienz unter Standardsubstitution mit Hydrocortison

E.1.1.1

Medical condition in easily understood language

Adrenal insufficiency

Nebenniereninsuffizienz

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10001130
E.1.2	Term	Addison's disease
E.1.2	System Organ Class	10014698 - Endocrine disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10052381
E.1.2	Term	Primary adrenal insufficiency
E.1.2	System Organ Class	10014698 - Endocrine disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluation of the pharmacokinetics of hydrocortisone after subcutaneous injection (s.c.) for use in adrenal emergency

Untersuchung der Pharmakokinetik der subkutanen Hydrocortisonapplikation

E.2.2

Secondary objectives of the trial

Evaluation of the safety and feasibility of hydrocortisone after subcutaneous injection (s.c.) for use in adrenal emergency

Untersuchung der Sicherheit der subkutanen Hydrocortisonapplikation

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

patients with chronic primary adrenal insufficiency due to autoimmune adrenalitis or bilateral adrenalectomy

Patienten mit chronischer primärer Nebenniereninsuffizienz, Morbus Addison oder Zustand nach bilateraler Adrenalektomie

E.4

Principal exclusion criteria

Diabetes mellitus, fever at time of investigation, oral contraception, pregnancy, breast feeding, renal failure, intolerance to the study drug or constituents

Diebetes mellitus, fieberhafter Infekt zum Zeitpunkt der Untersuchung, orale Kontrazeption, Schwangerschaft, Stillzeit, Niereninsuffizienz, bekannte Allergie gegenüber Bestandteilen des Prüfpräparates

E.5 End points

E.5.1

Primary end point(s)

The primary clinical endpoint is the time to cortisol levels required in critical illness (>1000 nmol/l). Comparison s.c. vs. i.m. and the number of patients achieving this level. The hypothesis is that this serum levels can be achieved within a critical time frame of 30 min after subcutaneous injection with good safety and higher patient acceptance compared to intramuscular administration. Further end points are pharmacokinetic data for assessment of bioequivalence: Cmax: maximal plasma concentration; Cmin: minimal plasma concentration; Cav: average plasma concentration; tmax: time passed since administration at which the plasma concentration maximum occurs; AUCt: area under the plasma concentration curve from administration to last observed concentration at time t. MRT: mean residence time; t1/2: plasma concentration half-life; Fluctuation: (Cmax - Cmin)/Cav.
Secondary end points are the safety of subcutaneous hydrocortisone administration and the response of ACTH levels to glucocorticoid administration as a second indirect measure of physiological glucocorticoid activity. Further patient acceptability of the different modes of glucocorticoid administration will be assessed.

Pharmakokinetik von Hydrocortison nach subkutaner Gabe,
Zeit bis zum Erreichen von Cortisolspiegeln, die als “sicher” bei schwerer Erkrankung erachtet werden (>36 µg/dl, >1000 nmol/l) nach subkutaner vs. intramuskulärer Gabe
pharmakokinetische Daten: Cmax: maximal plasma concentration; Cmin: minimal plasma concentration; Cav: average plasma concentration; tmax: time passed since administration at which the plasma concentration maximum occurs; AUCt: area under the plasma concentration curve from administration to last observed concentration at time t. MRT: mean residence time; t1/2: plasma concentration half-life; Fluctuation: (Cmax - Cmin)/Cav.

E.5.1.1

Timepoint(s) of evaluation of this end point

blood sampling after 5 to 240 min after administration of the study medication, final assessment by questionnaires after last intervention.

Blutentnahmen nach 5 bis 240 min nach Verabreichung des Hydrocortisonpräparats (an drei untersuchungstagen)

E.5.2

Secondary end point(s)

safety and tolerability by the patient compared to intramuscular administration

Sicherheit und Patientenakzeptanz der subkutanen Gabe im Vergleich zur intramuskulären Gabe.

E.5.2.1

Timepoint(s) of evaluation of this end point

final assessment by questionnaires after last intervention

Untersuchungsende mit Beantwortung eines Fragebogens

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

E.6.8

Bioequivalence

Yes

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

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)

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

Last entry in the patient diary (three days after final study visit with final adminsitration of the study medication) of the last patient included.

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 2011-10-06.

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.4.2.2

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)

No difference in long term treatment of the clinical condition of study participants. Single treatments are performed within the trial. Patients are seen on a regular basis in our outpatient clinic.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-10-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-07-13

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials