Stable, effort-induced angina pectoris MedDRA version: 13.1 Level: LLT Classification code 10049194 Term: Stable angina pectoris System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Pentalong®
Product Name: Pentalong®
Product Code: not applicable
Pharmaceutical Form: Tablet
INN or Proposed INN: pentaerythritol tetranitrate
CAS Number: 78 11-5
Current Sponsor code: no
Sponsors
Actavis Deutschland GmbH & Co.Kg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: At the end of the run-in period the following inclusion criteria must be fulfilled: 1. Second qualifying ETT meeting all of the following criteria: - Positivity criteria: occurrence of limiting angina and ST-segment depression of at least 1 mm as compared to resting ECG, (horizontal or down sloping and persisting for at least 0.08 seconds after J-point, on at least three consecutive complexes) between 2.5 and 12 minutes of initiation with modified Bruce treadmill ergometer protocol. If the ETT is interrupted before reaching positivity for any reason, the patient will not be included. - Stability criteria: Difference between selection (Day -7) and inclusion (Day 0) ETT measurements has to be within 20% of the Day 0 value. 2. At least 4 anginal attacks in the 4 week period preceding randomisation 3. Compliance to treatment during the run-in period, i.e. placebo on top of background treatment (calculated compliance at least 85%, in addition, patient should not have missed more than one full daily dose). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients will not be included in the trial if one of the following criteria applies: General exclusion criteria: 1. Incapability of understanding the language in which the information for the patient is given; 2. Presence or history of drug or alcohol abuse; 3. Presence of malignant disease in the past 5 years; 4. The patient is a woman of childbearing potential who does not use a reliable method of contraception; (Note: A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner); 5. The patient is a pregnant or breast feeding woman; 6. Participation in a concurrent clinical trial or in another trial within the past 4 weeks; 7. Repeated participation in this trial; 8. Anticipated poor medication compliance; 9. The patient is the investigator him/herself. Trial-specific exclusion criteria: 1. Recent acute myocardial infarction, coronary bypass surgery less than 3 months before inclusion or coronary angioplasty less than 6 months before inclusion; 2. Unstable angina, Prinzmetal angina or microvascular angina; 3. Angina pectoris symptoms typically induced by factors other than physical exertion; 4. Known high-grade left main coronary artery disease that has not been surgically bypassed or mechanically improved; 5. History of untreated, clinical relevant mitral insufficiency, constrictive pericarditis, pericardial tamponade, severe pulmonary hypertension, aortic stenosis, hypertrophic obstructive cardiomyopathy or other causes of left ventricular outflow tract obstruction. If such disorders are treated, the treatment should be confirmed by echocardiogram not older than 6 months. The clinical relevance of the disorders is left to the discretion of the investigator; 6. Hyperresponsitivity or contraindications to nitrovasodilators in particular PETN and nitroglycerin; 7. Anticipated elective percutaneous transluminal coronary angioplasty (PTCA) in the upcoming 12 weeks; 8. Patient who cannot perform exercise tests, in particular for muscular, joint and/or skeletal reasons; 9. Clinically significant heart disease other than coronary artery disease; 10. Congestive heart failure stage III or IV New York heart association (NYHA); 11. Symptomatic hypotension (<100mmHg, dizziness, orthostatic dysregulation); 12. Uncontrolled hypertension (systolic blood pressure at rest at above 180 mmHg or diastolic blood pressure at rest above 100 mmHg); 13. Atrial fibrillation, flutter, pacemaker or cardioverter-defibrillator implantation; 14. ECG abnormalities that would confound ETT interpretation; 15. Repolarisation disturbance seen in the ECG at baseline; 16. Hepatic disorders (alanine aminotransferase [ALT] more than 3 times normal value), renal failure (serum creatinine level above 180 µmol/l); 17. Electrolyte disorders; 18. Anaemia (haemoglobin below 10.0 mg/dl); 19. Thyroid disorders (unless stable and controlled by thyroxin treatment for at least 3 months); 20. Any treatment with unauthorised concomitant medication that could not be interrupted for the duration of the trial; 21. Treatment with amiodarone within 3 months prior to selection; 22. Use of bepridil < 7days before screening 23. Use of digitalis/cardiac glycosides 6 months prior to selection; 24. Inability or lack of consent to wash
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to show superiority of PETN over placebo in the treatment of patients with stable, effort-induced angina pectoris receiving anti-anginal background therapy in a modern, regulatory guideline compliant trial.;Secondary Objective: A secondary objective is to evaluate the safety and tolerability of PETN 80 mg bid for treatment of adult subjects with stable, effort-induced angina pectoris.;Primary end point(s): Primary efficacy: Change in Total Exercise Duration (TED) [seconds]) from baseline after 12 weeks of treatment with PETN 80 mg bid as compared to placebo bid assessed in the trough between the morning and the midday dose, (i.e. at 5 h after intake of morning dose of study medication). Secondary efficacy: - Angina attack frequency, intensity, and duration (according to patient diary); - Change in time to onset of anginal pain on ETT after 6 and 12 weeks of treatment; - Change in exercise capacity (METs) after 6 and 12 weeks of treatment - Concomitant use of short-acting nitrates (according to patient diary) - Change in time to limiting angina (TLA, seconds) during ETT after 6 and 12 weeks of treatment - Change in TED (seconds) during ETT after 6 weeks of treatment - Change in time to 1 mm ST segment depression (TST) (horizontal or down-sloping for more than 0.08 s after the J point) after 6 and 12 weeks of treatment; - Angina attack intensity, and duration (according to patient diary); - Change in Health related quality of life scores after 12 weeks of treatment; - Borg scale. | — |
Countries
Bulgaria, Germany, Hungary, Iceland, Spain
Outcome results
None listed