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

Duchenne Muscular Dystrophy (DMD) Clinical Trial

— ISOFEN1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01478022
• Other study ID #: ISOFEN1
• Status: Completed
• Phase: Phase 1
• Start date: October 2011
• Est. completion date: March 2016

Study information

• Verified date: August 2018
• Source: Parent Project, Italy
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 27 Years

Eligibility

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

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy (DMD)
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Isosorbide Dinitrate
Isosorbide Dinitrate 10 mgx2, daily, capsules
• Ibuprofen
Ibuprofen 200 mg daily, capsules

Other:
• Ibuprofen and Isosorbide Dinitrate combination
Ibuprofen 200 mg and Isosorbide Dinitrate 20 mg combination daily dose

Locations

Country	Name	City	State
Italy	Clinical Phase 1 Unit - Luigi Sacco Hospital	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Parent Project, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Adverse Events	Adverse Events registration At visit 2, visit 3 and visit 4	9 days
Secondary	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