None listed
Conditions
Brief summary
A randomized, placebo-controlled Phase 2a study to test the efficacy and safety of cilnidipine alone and in combination with tadalafil in participants at least 18 years of age diagnosed with severe secondary Raynaud’s disease (Raynaud’s Condition Score [RCS] greater than o r equal 40 and at least a 2-phase colour change in fingers of pallor, cyanosis, and/or reactive hypermedia in response to cold exposure or emotion) mostly resulting from SSc and exhibiting regular and frequent RP attacks (averaging at least one attack per day) during the Screening period. Double-blind, Placebo-controlled, Parallel-group, Dose Selection to assess the safety and efficacy of two doses of cilnidipine (10 mg and 20 mg), alone and in combination with tadalafil. Participants will be randomized to one of six prespecified treatment arms. During the study 36 participants will receive treatments in a blinded fashion. Placebo tablets (matching cilnidipine) and placebo capsules (matching tadalafil), for oral administration, will be provided to the site as well as the investigational treatments (cilnidipine and tadalafil). Medications will be dispensed during the preceding in-clinic study visit for self-administration by the participant. Each Dosing Period will last for 12 days (allowing for a variance window of -2 days [d10] or +2 days [d14] ) in which participants will take daily doses of assigned treatment in the morning. For each day of dosing, participants will take one capsule and one tablet to blind the active therapy being received. Dropouts will not be replaced. Primary Efficacy Endpoint: Percentage change from baseline in frequency of weekly RP attacks. Safety Endpoints: Incidence of adverse events (AEs) and serious adverse events (SAEs), including clinically significant vital signs from the time of randomization until 7 days following the last protocol dose.
Interventions
In this dose-finding study (part A of a combined protocol), each participant will self-administer 1 tablet and 1 capsule daily for 12 consecutive days. Depending on randomisation, they will receive either 10 mg or 20 mg Cilnidipine tablet or placebo tablet, and 5 mg of Tadalafil capsule or placebo capsule.
Sponsors
AISA Pharma Australia Pty. Ltd.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants at least 18 years of age diagnosed with severe secondary Raynaud’s disease (Raynaud’s Condition Score [RCS] greater than or equal to 40 and at least a 2-phase color change in fingers of pallor, cyanosis, and/or reactive hypermedia in response to cold exposure or emotion) mostly resulting from SSc and exhibiting regular and frequent RP attacks (averaging at least one attack per day) during the Screening period.
Exclusion criteria
1. A participant who meets any of the following exclusion criteria must be excluded from the study: 1. Primary Raynaud’s disease. 2. History of Raynaud’s attacks of sufficient severity as to require in-patient hospitalization (within the last 6 months). 3. The SBP of < 95 mm Hg during Randomization visit (Day 0). 4. Pulmonary hypertension requiring specific therapy for this condition. 5. Participants with an allergy to dihydropyridine CCBs that results in clinical findings such as profound hypotension, hives, rash, urticaria, wheezing and changes in breathing (Common treatment limiting adverse events [AEs] that occur with CCBs nifedipine and amlodipine such as edema, headache, heart rate changes, tachycardia, fatigue, constipation, flushing, drowsiness, dizziness should not limit enrollment into this study). 6. History of other chronic pain condition that could confound recording of pain scores during the study period. 7. Any prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that in the opinion of the Investigator(s), would contraindicate administration of the study medication, or interfere with the study evaluations, or interfere with the participants ability to comply with the study protocol. 8. Cognitive or language difficulties that would impair completion of the study assessments. 9. Use of any investigational product (IP) or investigational medical device or participation in investigational drug studies within 30 days prior to enrollment in the study. 10. Those receiving nitrates, alpha blockers, PDE inhibitors (outside of stable administration for PAH), prostacyclins or endothelin antagonists. 11. History of orthostatic hypertension, dizziness or fainting spells, acute coronary or cerebrovascular event within 3 months of study enrollment. 12. History of major thoracic, abdominal, or vascular surgery within 6 months of study enrollment; History of sympathectomy. 13. Severe cardiomyopathy, severe valvular heart disease, chronic kidney disease (CKD) stage 3 or greater, evidence of malignancy, end stage lung disease. 14. Pregnant or lactating women. 15. Women of childbearing potential (WOCBP) unable to comply with contraceptive requirements during the study period. 16. Males with partners who are WOCBP and are unable to comply with the contraceptive requirements during the study. 17. History of drug or excess alcohol use that in the opinion of the Investigator(s) would affect the participant’s ability to reliably participate in the study. NHMRC guidelines for regular alcohol consumption in healthy adults are no more than 10 standard drinks per week and no more than four standard drinks on any one day. 18. Use of tobacco products of any type in the preceding one month and for the duration of the study.
Outcome results
None listed