Clinical Trials Register

Summary
EudraCT Number:	2010-024005-13
Sponsor's Protocol Code Number:	3098009
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-12-30
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

UK - MHRA

A.2

EudraCT number

2010-024005-13

A.3

Full title of the trial

Efficacy of ORM-12741 for prevention of cold-induced vasospasm; a randomised, double-blind, placebo-controlled, single centre crossover study in patient with Raynaud's phenomenon secondary to systemic sclerosis

A.3.1

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

A study of ORM-12741 for the prevention of blood vessel spasm brought on by cold temperature.

A.3.2

Name or abbreviated title of the trial where available

Reino

A.4.1

Sponsor's protocol code number

3098009

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	Orion Corporation Orion Pharma
B.1.3.4	Country	Finland
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	Orion Corporation Orion Pharma
B.4.2	Country	Finland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Orion Corporation Orion Pharma
B.5.2	Functional name of contact point	Angela Ruck
B.5.3	Address:
B.5.3.1	Street Address	2-4 Weekday Cross Fletcher Gate
B.5.3.2	Town/ city	Nottingham
B.5.3.3	Post code	NG1 2GB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441159487138
B.5.5	Fax number	00441159487139
B.5.6	E-mail	clinicaltrials@orionpharma.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	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	ORM-12741
D.3.2	Product code	ORM-12741
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ORM-12741
D.3.9.3	Other descriptive name	alpha-2C AR antagonist
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.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	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	ORM-12741
D.3.2	Product code	ORM-12741
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ORM-12741
D.3.9.3	Other descriptive name	Alpha-2C AR antagonist
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	30
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	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Raynaud's phenomenon secondary to systemic sclerosis (Raynaud's syndrome)

E.1.1.1

Medical condition in easily understood language

Blood vessel spasm brought on by cold temperature in patients with Raynauds phenomenon secondary to systemic sclerosis.

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

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	10037914
E.1.2	Term	Raynaud's syndrome
E.1.2	System Organ Class	10047065 - Vascular disorders

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 efficacy of ORM-12741 in the attenuation of a cold-induced reduction in finger blood flow and temperature in subjects with Raynaud's Phenomenon (RP) secondary to systemic sclerosis in a controlled environment.

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability of ORM-12741 in subjects with RP secondary to systemic sclerosis, and to assess dose-response relationship in terms of the effect on finger blood flow and temperature.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Written informed consent (IC) obtained.
2.Age of 18-75 years (inclusive).
3.Body mass index (BMI) between 18-30 kg/m2 (inclusive).
4.Male or female patients with a diagnosis of active RP secondary to systemic sclerosis. Active RP will be defined as a history of cold sensitivity associated with colour changes of cyanosis or pallor, as well as of at least 2 attacks daily or at least 6 attacks weekly during the winter months. Diagnosis of systemic sclerosis will be defined by The European League Against Rheumatism (EULAR) criteria (Matucci-Cerinic M et al., 2009).
5.Stable symptoms for RP and medication requirements within 2 months prior to screening.
6.Negative pregnancy test for females of childbearing potential.

E.4

Principal exclusion criteria

1.Treatment with nitrates.
2.Changes in dosing of calcium channel blockers (CCBs) within 1 month prior to the screening or during the study.
4.Changes in dosing of other vasoactive medications within 1 month prior to the screening or during the study.
5.Inability to refrain from smoking for at least 12 hours prior to and during the treatment visits.
6.Current active ischemic digital ulcer and/or tissue gangrene.
7.History of sympathectomy.
8.Upper extremity deep vein thrombosis or lymphoedema within 3 months prior to screening.
9.Clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological, psychiatric, or malignant disorder or any other major concurrent illness that in the opinion of the investigator would interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part into the study.
10.Supine HR > 100 bpm after a 10-minute rest at screening visit.
11.Supine systolic BP (SPB) > 160 or diastolic BP (DPB) > 100 mmHg after a 10-minute rest at screening visit.
12.Any other abnormal value of laboratory, vital signs or electrocardiogram (ECG) which may in the opinion of the investigator interfere with the interpretation of the study results or cause health risk for the subject if he/she takes part into the study.
13.Pregnant or breast feeding or considering pregnancy in the next 4 months.
14.Female subjects of childbearing potential (i.e. menstruating or less than 2 years postmenopausal) if they are not using proper contraception (hormonal contraception, intrauterine device (IUD) or surgical sterilisation, spermicidal foam in conjunction with condom on male partner).
15.Subjects with pre-planned elective surgery during the estimated study period.
16.Blood donation or loss of significant amount of blood within 30 days prior to the screening.
17.Participation in a drug study within 30 days prior to the screening.
18.Known hypersensitivity to the active substance or to any excipients of the drug.
19.Recent or current (suspected) drug abuse.
20.Recent or current alcohol abuse (regular drinking more than 14 units per week for females or 21 units per week for males; 1 unit = 4 cl spirits or equivalent).
21.Inability to refrain from consuming caffeine-containing beverages for at least 12 hours prior to and during the treatment visits e.g. propensity in getting headache when refraining from caffeine-containing beverages.
22.Inability to participate in all treatment periods.
23.Unsuitable veins for repeated venipuncture or for cannulation.
24.The subject is not able to swallow test capsule at screening visit.
25.Any other condition that in the opinion of the investigator would interfere with the interpretation of the study results or constitute a health risk for the patient if he/she takes part in the study.

E.5 End points

E.5.1

Primary end point(s)

Effects of treatments on finger blood flow will be assessed by measuring finger temperature and skin blood flow index by Laser Doppler Imaging (LDI).
Continuous raw data from the finger temperature and LDI measurements will then be transformed to the following variables:
•area above the time-response curve,
•minimum measurement,
•time to minimum measurement,
•time to recovery of 70% of the baseline measurement, and rates of change in temperature and blood flow during decrease and recovery.

E.5.1.1

Timepoint(s) of evaluation of this end point

Measurement of the finger temperature and skin blood flow index by Laser Doppler imaging (LDI) at baseline before treatment, baseline after treatment, during exposure to cold challenge and during recovery

E.5.2

Secondary end point(s)

The concentrations of adrenaline and noradrenaline in plasma will be determined in order to assess response to the cold challenge and the study treatment (PD).
Concentrations of ORM-12741 and the major metabolite ORM-13720 in plasma will be determined (PK).
Assessment of safety and tolerability.

E.5.2.1

Timepoint(s) of evaluation of this end point

PK & PD before the IMP dosing, 31 min. after dosing and 91 min. after dosing.
Safety and tolerability until the end-of study visit

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

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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)

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.8.4.1

Number of sites anticipated in 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

Information not present in EudraCT

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

Last visit of the last subject undergoing the trial

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)

As per protocol

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

2011-02-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-03-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2011-12-14

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