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

Sponsor

Parent Project, Italy (Other)

Overall Status

Completed

CT.gov ID

NCT01478022

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy (DMD)	Drug: Isosorbide Dinitrate Drug: Ibuprofen Other: Ibuprofen and Isosorbide Dinitrate combination	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Isosorbide Dinitrate 20 mg Isosorbide Dinitrate 10 mg b.i.d	Drug: Isosorbide Dinitrate Isosorbide Dinitrate 10 mgx2, daily, capsules Other Names: Diniket 10 mg
Active Comparator: Ibuprofen 200 mg Ibuprofen 200 mg daily, capsule	Drug: Ibuprofen Ibuprofen 200 mg daily, capsules Other Names: Antalgil 200 mg
Experimental: Isosorbide dinitrate and Ibuprofen Isosorbide dinitrate 20 mg daily and Ibuprofen 200 mg daily	Other: Ibuprofen and Isosorbide Dinitrate combination Ibuprofen 200 mg and Isosorbide Dinitrate 20 mg combination daily dose Other Names: Antalgil 200 mg and Diniket 10 mg

Arm

Intervention/Treatment

Active Comparator: Isosorbide Dinitrate 20 mg

Isosorbide Dinitrate 10 mg b.i.d

Drug: Isosorbide Dinitrate

Isosorbide Dinitrate 10 mgx2, daily, capsules

Other Names:

Diniket 10 mg

Active Comparator: Ibuprofen 200 mg

Ibuprofen 200 mg daily, capsule

Drug: Ibuprofen

Ibuprofen 200 mg daily, capsules

Other Names:

Antalgil 200 mg

Experimental: Isosorbide dinitrate and Ibuprofen

Isosorbide dinitrate 20 mg daily and Ibuprofen 200 mg daily

Other: Ibuprofen and Isosorbide Dinitrate combination

Ibuprofen 200 mg and Isosorbide Dinitrate 20 mg combination daily dose

Other Names:

Antalgil 200 mg and Diniket 10 mg

Outcome Measures

Primary Outcome Measures

Pharmacokinetic parameter: AUC 0-12 [At period I, II and III with 7 days intervals between periods]
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

Secondary Outcome Measures

C max [At period I, II and III with 7 days intervals between periods]
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 [At period I, II and III with 7 days intervals beteween periods]
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 [9 days]
Adverse Events registration At visit 2, visit 3 and visit 4
Vital signs [9 days]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 27 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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