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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Open, Randomized, 3 Period Cross-over Design, in Healthy Volunteers to Compare the Pharmacokinetics Profiles of 3 Treatments: ISO 20, IBU 200 and IBU Plus ISO Combinations (200 + 20) Administered Per os as Single Doses

Conditions
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Duchenne Muscular Dystrophy (DMD)

Intervention / Treatment
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* Drug: Isosorbide Dinitrate
* Drug: Ibuprofen
* Other: Ibuprofen and Isosorbide Dinitrate combination


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 27 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Isosorbide Dinitrate 20 mg<br>Isosorbide Dinitrate 10 mg b.i.d | Drug: Isosorbide Dinitrate<br>* Isosorbide Dinitrate 10 mgx2, daily, capsules<br>* Other names: Diniket 10 mg;|
| Active Comparator: Ibuprofen 200 mg<br>Ibuprofen 200 mg daily, capsule | Drug: Ibuprofen<br>* Ibuprofen 200 mg daily, capsules<br>* Other names: Antalgil 200 mg;|
| Experimental: Isosorbide dinitrate and Ibuprofen<br>Isosorbide dinitrate 20 mg daily and Ibuprofen 200 mg daily | Other: Ibuprofen and Isosorbide Dinitrate combination<br>* Ibuprofen 200 mg and Isosorbide Dinitrate 20 mg combination daily dose<br>* Other names: Antalgil 200 mg and Diniket 10 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter: AUC 0-12 | Area under the time-concentration curve (AUC 0-12) 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 | At period I, II and III with 7 days intervals between periods | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C max | 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 | At period I, II and III with 7 days intervals between periods | 
| T max | 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 | At period I, II and III with 7 days intervals beteween periods | 
| Adverse Events | Adverse Events registration At visit 2, visit 3 and visit 4 | 9 days | 
| Vital signs | 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 | 9 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DMD, Duchenne, Muscular Dystrophy