Peripheral arterial occlusive disease (PAOD, femoro-popliteal stenosis) and intermittent claudication (Fontaine stage IIb, pain-free walking distance < 200 m), lasting for at least 3 months to ensure clinical stability MedDRA version: 20.0 Level: LLT Classification code 10074576 Term: Peripheral arterial occlusive disease Fontaine stage IIb System Organ Class: 100000004866
Conditions
Interventions
Product Name: Nitroglycerin sublingual powder
Pharmaceutical Form: Oral powder in sachet
INN or Proposed INN: Nitroglycerin
CAS Number: 55-63-0
Sponsors
G. Pohl-Boskamp GmbH & Co.KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female outpatients, aged = 18 years 2) Ability to exercise a treadmill test 3) Confirmation of clinical diagnosis of PAOD as objective evidence of Fontaine stage IIb PAOD i.e.: a) reduced ankle systolic blood pressure (ABI =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Asymptomatic PAOD Patients, equivalent to PAOD Fontaine stage I 2. PAOD-patients with critical limb ischemia (CLI), equivalent to EMA´s or Fontaine´s PAOD-stages III and IV 3. Any kind of revascularization (endovascular, surgical) in the iliac and/or leg arteries within 3 months prior to Visit 1 4. Current unstable angina 5. History of congestive heart failure, NYHA class III or IV 6. Use of confounding medications within the last 4 weeks prior to Visit 1 – e.g. vasoactive compounds like Cilostazol or Naftidrofuryl 7. Patients with significant disease of the cardiac valves or symptomatic untreated arrhythmias 8. Other diseases limiting exercise capacity (angina pectoris, heart failure, respiratory diseases, orthopedic diseases, neurological disorders) 9. Uncontrolled hypertension (> 180/100mmHg) or hypotension (supine SBP 3x upper range of normality 15. Know hypersensitivity to any ingredient in the product formulation 16. Pregnancy or lactation period 17. Women of childbearing potential without an effective contraceptive method 18. Planned surgical intervention requiring hospitalization during the clinical trial 19. Previous inclusion in the present clinical trial or parallel participation in another clinical trial (up to 8 weeks before Visit 1) 20. Incapability of understanding nature, meaning and consequences of the clinical trial 21. Patient unable to read and / or write 22. Patients in custody by juridical or official order 23. Patients, who are members of the staff of the trial center, staff of the sponsor or involved 24. Clinical Research Organizations (CROs), the investigator him- / herself or close relatives of the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: At Visit 7 = after 12 weeks of treatment. ; Main Objective: The study is conducted to assess the efficacy and safety of nitroglycerin in a scheduled forced titration design of sublingual GTN. In order to avoid adverse reactions like e.g. headaches, the dosing regimen comprises a low initial dose with weekly increments to a sub-chronic target dose of sublingual nitroglycerin on walking distance in PAOD-patients with femoro-popliteal stenosis and intermittent claudication (stage II) relative to placebo. Primary Objectives are: 1) Showing improvement in initial walking distance (ICD) according to a treadmill protocol with constant workload (3.2 km/h and 12% grade). 2) Showing improvement in walking distance: Absolute claudication distance (ACD) according to a treadmill protocol with constant workload (3.2 km/h and 12% grade). The study is a proof of concept study. ; Secondary Objective: 1) Frequency and intensity of adverse events (AE), blood pressure/heart rate, in particular: headache, hypotension/orthostasis (dizziness, lightheadedness, syncope/presyncope) 2) Changes in the ankle-brachial-index (ABI) 3) Assessment of adverse events 4) Changes in patient´s quality of life ;Primary end point(s): One primary endpoint is defined as the increase in “walking distance” measured as initial claudication distance (ICD) at Visit 7 (end of treatment period) compared to baseline. A further primary endpoint is the walking distance by absolute claudication distance (ACD) at Visit 7 (end of treatment period) compared to baseline. For both primary endpoints a constant workload treadmill protocol is used (3.2 km/h and 12% grade). The relationship between worktime and workload follows a linear function. The justification for the selection of both primary endpoints is based | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Secondary endpoints related to efficacy will be assessed at visit 7, visit 8 and visit 9. Scondary enpoints related to safety will be evaluated starting after visit 2 throughout the whole Trial. ; Secondary end point(s): 1. Walking distance by initial claudication distance (ICD) at Visit 8 and Visit 9 (both during follow-up phase) will be tested for superiority analogously to the respective primary endpoint. A constant workload treadmill protocol is used (3.2 km/h and 12% grade). 2. Walking distance by absolute claudication distance (ACD) at Visit 8 and Visit 9 (both during follow-up phase) will be tested for superiority analogously to the respective primary endpoint. A constant workload treadmill protocol is used (3.2 km/h and 12% grade). 3. Ankle-brachial-index (ABI): Changes of ABI during the treatment course at Visit 7, 8 and 9 and in comparison to Visit 2 (baseline) will be analyzed by MMRM analysis of covariance using ABI differences from baseline as dependent variable, baseline ABI as covariate, visit (repeated), treatment and center as fixed effects. The treatment effect of ABI at Visit 7, Visit 8 and Visit 9 will be calculated from the model. 4. The following Questionnaires a. EQ-5D b. ICQ will be analysed at Visit 7 and 9 and in comparison to Visit 2 (baseline) by MMRM analysis of covariance using differences of the respective score from baseline as dependent variable, baseline score as covariate, visit (repeated), treatment and center as fixed effects. The treatment effects of ED-5D and ICQ at Visit 7, Visit 8 and Visit 9 will be calculated from the model. 5. Adverse events: The MedDRA system will be used to code adverse events. AEs (preferred terms) will be tabulated for each treatment group by system organ class according to MedDRA. The tables wi | — |
Countries
Germany
Contacts
Public ContactClinical Research
G. Pohl-Boskamp GmbH & Co.KG
Outcome results
None listed