None listed
Conditions
Brief summary
Double-blind, Randomized, Placebo-controlled, Crossover study to assess the safety and efficacy of cilnidipine (20 mg) alone. Participants will be randomized to drug first, or placebo first, followed by the alternate treatment in a subsequent dosing period. 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-d14]) in which participants will take daily doses of assigned treatment in the morning. For each day of dosing, participants will take active drug or matching placebo to blind the active therapy being received.
Interventions
Cilnidipine (20mg) oral tablet once daily for 12 ± 2 days, with a 4 (± 1) day washout period between dosing periods in the crossover design.
Exact duration within these windows is on a case-by-case basis considering both physician and participant availability.
Medication usage is recorded in a daily diary and any unused doses returned at the conclusion of the dosing period.
Sponsors
AISA Pharma Australia Pty. Ltd.
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
- Severe secondary Raynaud’s disease (with patient reported RCS at baseline of at least 20) based on ACR criteria mostly resulting from SSc. - Regular and frequent Raynaud’s attacks (averaging at least one attack per day) during the Screening week (in participants with at least a 2-phase color change in fingers of pallor, cyanosis, and/or reactive hyperemia in response to cold exposure or emotion). - Willingness to complete the daily diary entry’s during the Screening period. - Participants must be willing and able to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures. - Willingness to forego therapies for Raynaud’s during study participation is preferred (except for selective serotonin reuptake inhibitors such as fluoxetine which should not be discontinued) Ongoing treatment with CCBs and other routine therapies for SSc-RP is permitted however, if it is not clinically feasible to stop therapy, the participant has been on a stable dose for the last 2 months and meets all eligibility criteria. Rescue therapy (with acetaminophen, nonsteroidal anti-inflammatory drug [NSAIDs], other codeine analgesics, fluoxetine, angiotensin II receptor blockers (ARBs) such as losartan) or CCBs will be allowed to manage breakthrough symptoms of SSc-RP but must be documented). - Participants who are on a stable dose (no change in the last 2 months) of a CCB for hypertension or PDE5 inhibitors for pulmonary hypertension may continue these agents at this stable dose as long as they meet other inclusion criteria during Screening. - Have agreed not to use (or initiate treatment with) other investigational therapies or unapproved therapies during the course of the study outside of protocol allowances for rescue medication (such medications include but are not limited to: nitroglycerin, topical creams, fenoldopam, nimodipine, amlodipine, fluoxetine, pregabalin, gabapentin, verapamil, sildenafil, tadalafil, vardenafil). - Women of childbearing potential (WOCBP) who have agreed to use an effective method of contraception during the study and for 30 days after the last study dose. Acceptable methods of birth control in this study include oral contraceptive, barrier control, or implanted devices. A woman must agree not to donate eggs (ova; oocytes) for purposes of reproduction for at least 30 days after last dose of study drug. - Post-menopausal females, aged over 45 years who have not had a period for at least 12 months, and are not using hormonal contraception, or females documented as permanently sterile (e.g., bilateral tubal ligation; hysterectomy, bilateral salpingectomy). - Negative urine pregnancy test on Randomization day (WOCBP only). - All sexually active men whose partner is a WOCBP (due to potential risk of drug exposure through the ejaculate) who agree to a barrier method of birth control during the study and for 30 days after the last dose of the study drug. All men must agree not to donate sperm for at least 30 days after receiving last dose of study drug. - Participants must have clinical laboratory values within normal range as specified by the testing laboratory at their most recent pre-screening sample, unless deemed not clinically significant by the Investigator or delegate. Lab sample may be within the last 2 months as long as there have been no significant clinical changes since the last labs and no new medications (e.g. Diuretics) have been introduced that are known to be associated with changes in clinical chemistry or hematology values (e.g. potassium with diuretics or cyclosporine associated with aplastic anemia).
Exclusion criteria
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. SBP of < 95 mm Hg during Randomization visit (Day 0). 4. 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 enrolment into this study). 5. History of other chronic pain condition that could confound recording of pain scores during the study period. 6. 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. 7. Cognitive or language difficulties that would impair completion of the study assessments. 8. Use of any investigational product (IP) or investigational medical device or participation in investigational drug studies within 30 days prior to enrolment in the study. 9. Those receiving nitrates (nitro-dur, nitroglycerin) or similar agents that have vasodilatory effects (eg. nicorandil) prescribed to treat angina, alpha blockers, PDE inhibitors, prostacyclins or endothelin antagonists for whom dose is not stable for > 2 months 10. History of orthostatic hypotension, dizziness or fainting spells, acute coronary or cerebrovascular event within 3 months of study enrolment. 11. History of major thoracic, abdominal, or vascular surgery within 6 months of study enrolment; History of sympathectomy in the hand which is symptomatic for RP. 12. Severe cardiomyopathy, severe valvular heart disease, chronic kidney disease (CKD) stage 3 or greater, evidence of malignancy, end stage lung disease. 13. Pregnant or lactating women. 14. Women of childbearing potential (WOCBP) unable to comply with contraceptive requirements during the study period. 15. Males with partners who are WOCBP and are unable to comply with the contraceptive requirements during the study. 16. History of drug (including recreational use of inhaled amyl nitrates or party poppers) 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. 17. Heavy smokers of tobacco products of any type (defined as >10 cigarettes per day). Light smokers who agree to keep their smoking stable for the duration of their trial participation are eligible.
Outcome results
None listed