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

This study has been terminated.
(Recommendation by study DSMC to the sponsor following interim analysis of 8 subjects.)
Sponsor:
Information provided by (Responsible Party):
Orion Corporation, Orion Pharma
ClinicalTrials.gov Identifier:
NCT01315899
First received: March 14, 2011
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Raynaud's Phenomenon
Drug: ORM-12471 30mg
Drug: ORM-12471
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Phase IIa Study of the Efficacy of ORM-12471 for Prevention of Cold-induced Vasospasm: a Randomised, Double-blind, Placebo-controlled, Single Centre Crossover Study in Patients With Raynaud's Phenomenon Secondary to Systemic Sclerosis

Resource links provided by NLM:


Further study details as provided by Orion Corporation, Orion Pharma:

Primary Outcome Measures:
  • Finger temperature measurements and laser doppler imaging of the hands [ Time Frame: 0-90minutes continuous measurement ] [ Designated as safety issue: No ]
    Finger temperature measurements and laser doppler imaging of the hands will be continually monitored from 0 minutes through to 90 minutes.


Enrollment: 15
Study Start Date: March 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ORM-12471 30mg Drug: ORM-12471 30mg
Given as a single dose once during the crossover study as per Williams design
Placebo Comparator: placebo Drug: placebo
Given once as a single dose during the study as per Williams crossover design
Experimental: ORM-12471 100mg Drug: ORM-12471
Given as a single dose once during the study as per Williams crossover design

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 Heart rate (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01315899

Locations
United Kingdom
Salford Royal NHS foundation Trust
Salford, Greater Manchester, United Kingdom, M6 8HD
Sponsors and Collaborators
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Ariane L Herrick, MB,ChB, MD Salford Royal NHS Foundation Trust
  More Information

Publications:
Herrick A, Murray A, Ruck A, Rouru J, Moore T, Whiteside J, et al. A double-blind placebo-controlled crossover trial of the alpha-2c adrenoceptor antagonist orm-12741 for prevention of cold-induced vasospasm in patients with systemic sclerosis. Abstracts of the American College of Rheumatology, Washington, USA. Arthritis Rheum 2012; 64:S636.

Responsible Party: Orion Corporation, Orion Pharma
ClinicalTrials.gov Identifier: NCT01315899     History of Changes
Other Study ID Numbers: 3098009
Study First Received: March 14, 2011
Last Updated: June 26, 2014
Health Authority: United Kingdom: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Orion Corporation, Orion Pharma:
Raynaud's phenomenon
Systemic sclerosis

Additional relevant MeSH terms:
Raynaud Disease
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 01, 2014