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

• Register: EUCTR
• Last refreshed on: 25 September 2012
• Main ID: EUCTR2010-024005-13-GB
• Date of registration: 30/12/2010
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation Orion Pharma
• Public title: A study of ORM-12741 for the prevention of blood vessel spasm brought on by cold temperature.
• Scientific title: 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 - Reino
• Date of first enrolment: 11/03/2011
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024005-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

United Kingdom

Contacts

• Name: Angela Ruck
• Affiliation: Orion Corporation Orion Pharma

• Name: Angela Ruck
• Affiliation: Orion Corporation Orion Pharma

Key inclusion & exclusion criteria

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Raynaud's phenomenon secondary to systemic sclerosis (Raynaud's syndrome)
MedDRA version: 14.0 Level: LLT Classification code 10037914 Term: Raynaud's syndrome System Organ Class: 10047065 - Vascular disorders

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: ORM-12741
Product Code: ORM-12741
Pharmaceutical Form: Capsule
Current Sponsor code: ORM-12741
Other descriptive name: alpha-2C AR antagonist
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: ORM-12741
Product Code: ORM-12741
Pharmaceutical Form: Capsule
Current Sponsor code: ORM-12741
Other descriptive name: Alpha-2C AR antagonist
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

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

Secondary Objective: 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.

Main Objective: 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.

Secondary Outcome(s)

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.

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

Secondary ID(s)

3098009

Source(s) of Monetary Support

Orion Corporation Orion Pharma