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

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

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Drug: Isosorbide Dinitrate; Drug: Ibuprofen; Other: Ibuprofen and Isosorbide Dinitrate combination

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20157
    • Clinical Phase 1 Unit - Luigi Sacco Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 25 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Parent Project, Italy
• Investigators: Principal Investigator: Emilio Clementi, Luigi Sacco Hospital - Phase I Department - Via G. B. Grassi 74 20157 Milano

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: November 14, 2011
• First Submitted That Met QC Criteria: November 22, 2011
• First Posted (Estimate): November 23, 2011

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 29, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: DMD; Duchenne; Muscular Dystrophy
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Ibuprofen; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: ISOFEN1