Efficacy of ORM-12741 for Prevention of Raynaud's Phenomenon (REINO)

Raynaud's phenomenon (RP) is a disorder of the digital blood vessels resulting in episodic impairment of blood flow. During an attack of RP which commonly affects the hands and feet these arteries contract briefly which limits the blood flow (this is called a vasospasm) and deprived of blood the skin turns white then blue. The aim of this study is to prove the concept that ORM-12741 can prevent these blood vessel spasms.

• Drug: ORM-12471 30mg
  Given as a single dose once during the crossover study as per Williams design
• Drug: ORM-12471
  Given as a single dose once during the study as per Williams crossover design
• Drug: placebo
  Given once as a single dose during the study as per Williams crossover design

• Experimental: ORM-12471 30mg
  Intervention: Drug: ORM-12471 30mg
• Placebo Comparator: placebo
  Intervention: Drug: placebo
• Experimental: ORM-12471 100mg
  Intervention: Drug: ORM-12471

Inclusion Criteria:

• Written informed consent obtained
• Age of 10-75 years (inclusive)
• Body mass index (BMI) between 10-30 kg/m2 (inclusive)
• Male or female patients with a diagnosis of active Raynaud's phenomenon (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 6 attacks weekly during the winter months. Diagnosis of systemic sclerosis will be defined by the European League Against Rheumatism (EULAR) criteria.
• Stable symptoms for RP and medication requirements within 2 months prior to screening
• Negative pregnancy test for females of childbearing potential

Exclusion Criteria:

• Treatment with nitrates
• Treatment with calcium channel blockers (CCBs)for indications other than the relief of RP symptoms
• Treatment with calcium channel blockers (CCBs) for the relief of RP symptoms that in the opinion of the investigator cannot be stopped from the screening visit until end of the last experimental session
• Changes in dosing of other vasoactive medications within 1 month prior to screening or during the study
• Smoking or smoking cessation using nicotine products within 3 months prior to screening
• Current active ischemic digital ulcer and/or tissue gangrene
• History of sympathectomy
• Upper extremity deep vein thrombosis or lymphoedema within 3 months prior to screening.
• 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 in the study
• Supine HR >100 beats per minute (bpm) after a 10 minute rest at screening
• Supine systolic BP (SBP)>160 or diastolic BP (DBP)>100 mmmHg after a 10 minute rest at screening visit
• Any other abnormal value of laboratory, vital signs or ECG which may in the opinion of the investigator interfere with the interpretation of the study results or cause a health risk for the subject if he/she takes part into the study.
• Pregnant or breast feeding or considering pregnancy in the next 4 months
• Female subjects of child bearing potential (i.e. menstruating or less than 2 years post menopausal) if they are not using proper contraception (hormonal contraception,intrauterine device [IUD] or surgical sterilisation, spermicidal foam in conjunction with condom on male partner)
• Subjects with pre-planned elective surgery during the estimated study period
• Blood donation or loss of a significant amount of blood within 30 days prior to screening
• Participation in a drug study within 30 days prior to screening
• Known hypersensitivity to the active substance or to any excipients of the drug
• Recent or current (suspected) drug abuse
• Recent or current alcohol abuse (regular drinking more than 14 units per week for females or 21 units per week for males 1 unit= 4cl of spirits or equivalent)
• Inability to refrain from consuming caffeine-containing beverages for at least 12 hours prior to and during treatment visits e.g propensity in getting headache when refraining from caffeine-containing beverages
• Inability to participate in all treatment periods
• Unsuitable veins for repeated venipuncture or for cannulation
• The subject is not able to swallow a test capsule at the screening visit
• 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