To Compare the Pharmacokinetics Profiles of ISO 20, IBU 200 and IBU Plus ISO Combinations 200 + 20 (ISOFEN1)

• C max [ Time Frame: At period I, II and III with 7 days intervals between periods ] [ Designated as safety issue: No ]
  C max of IBU and ISO given concomitantly compared to AUCs of ISO alone and IBU alone. Time points: = at pre dose, 30, 60, 90, 120, 150, 180, 210, 240 min and 5, 6, 8, 10 and 12 hrs post dose
• T max [ Time Frame: At period I, II and III with 7 days intervals beteween periods ] [ Designated as safety issue: No ]
  T max of IBU and ISO given concomitantly compared to AUCs of ISO alone and IBU alone. Time points: = at pre dose, 30, 60, 90, 120, 150, 180, 210, 240 min and 5, 6, 8, 10 and 12 hrs post dose
• Adverse Events [ Time Frame: 9 days ] [ Designated as safety issue: Yes ]
  Adverse Events registration At visit 2, visit 3 and visit 4
• Vital signs [ Time Frame: 9 days ] [ Designated as safety issue: Yes ]
  Pulse rate and blood pressure (Diastolic and Systolic) measurements in sitting position at pre-dose, and 1 and 3 hours after study drug intake. Complete physical examination At visit 2, visit 3 and visit 4

This study will evaluate the pharmacokinetics plasma profile of 3 treatments: ISO 20, IBU 200 and IBU and ISO combinations (200 +20) given in single dose.

This study is being conducted to support the submission for new indication in treatment of the combinations of Isosorbide Dinitrate and Ibuprofen as a treatment for Duchenne muscular dystrophy.

This trial is designed to define drug interactions following the combined administration of Isosorbide Dinitrate, a NO donor, and ibuprofen, NSAID, a through pharmacokinetics approach.

Both ibuprofen and Isosorbide Dinitrate were licensed worldwide. Ibuprofen is approved for use in adults and children; Isosorbide is approved for use in adults. Ibuprofen is currently used in pediatric patients as a first line anti-inflammatory and antipyretic agent. Consensus exists that among NSAIDs ibuprofen is the one endowed with less adverse effects (see note 66 of the Italian Drug Agency AIFA and MEA). No specific studies concerning safety and tolerability of ISDN in pediatric patients have been reported.

• Drug: Isosorbide Dinitrate
  Isosorbide Dinitrate 10 mgx2, daily, capsules
  Other Name: Diniket 10 mg
• Drug: Ibuprofen
  Ibuprofen 200 mg daily, capsules
  Other Name: Antalgil 200 mg
• Other: Ibuprofen and Isosorbide Dinitrate combination
  Ibuprofen 200 mg and Isosorbide Dinitrate 20 mg combination daily dose
  Other Name: Antalgil 200 mg and Diniket 10 mg

• Active Comparator: Isosorbide Dinitrate 20 mg
  Isosorbide Dinitrate 10 mg b.i.d
  Intervention: Drug: Isosorbide Dinitrate
• Active Comparator: Ibuprofen 200 mg
  Ibuprofen 200 mg daily, capsule
  Intervention: Drug: Ibuprofen
• Experimental: Isosorbide dinitrate and Ibuprofen
  Isosorbide dinitrate 20 mg daily and Ibuprofen 200 mg daily
  Intervention: Other: Ibuprofen and Isosorbide Dinitrate combination

Inclusion Criteria:

• Healthy free-living
• Males between the age of 18 and 27
• Normal ECG
• Body Mass Index of 19.0-29.0 (Kg/m2)
• Subject healthy in the opinion of the Investigator
• Signed informed consent after verbal and written information

Exclusion Criteria:

• Clinically significant underlying systemic illness that may preclude the subject's ability to complete the trial
• Any Gastrointestinal conditions which, in the opinion of the Investigator, may interfere with the absorption of the drug or render the subjects unable to take oral medication (gastric ulcer, peptic ulcer, stomach acid, frequent diarrhea, gastrointestinal surgery)
• History of the following cardiac diseases SBP <120 mmHG or DBP < 80 mmHg
• Platelet count < 100000/mm3
• History of recurrent headache
• History of ongoing or clinically relevant glaucoma
• History of alcohol, drug or medication abuse within the past 2 years
• Treatment with norepinephrine, acetylcholine and histamine
• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation
• Participation in another study phase 1 with any investigational product within 6 months of screening