To Compare the Pharmacokinetics Profiles of ISO 20, IBU 200 and IBU Plus ISO Combinations 200 + 20 (ISOFEN1)
Primary Purpose
Duchenne Muscular Dystrophy (DMD)
Status
Completed
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
Isosorbide Dinitrate
Ibuprofen
Ibuprofen and Isosorbide Dinitrate combination
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy (DMD) focused on measuring DMD, Duchenne, Muscular Dystrophy
Eligibility Criteria
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
Sites / Locations
- Clinical Phase 1 Unit - Luigi Sacco Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Experimental
Arm Label
Isosorbide Dinitrate 20 mg
Ibuprofen 200 mg
Isosorbide dinitrate and Ibuprofen
Arm Description
Isosorbide Dinitrate 10 mg b.i.d
Ibuprofen 200 mg daily, capsule
Isosorbide dinitrate 20 mg daily and Ibuprofen 200 mg daily
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
Adverse Events
Adverse Events registration At visit 2, visit 3 and visit 4
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
Full Information
NCT ID
NCT01478022
First Posted
November 14, 2011
Last Updated
August 29, 2018
Sponsor
Parent Project, Italy
1. Study Identification
Unique Protocol Identification Number
NCT01478022
Brief Title
To Compare the Pharmacokinetics Profiles of ISO 20, IBU 200 and IBU Plus ISO Combinations 200 + 20
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Parent Project, Italy
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy (DMD)
Keywords
DMD, Duchenne, Muscular Dystrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Isosorbide Dinitrate 20 mg
Arm Type
Active Comparator
Arm Description
Isosorbide Dinitrate 10 mg b.i.d
Arm Title
Ibuprofen 200 mg
Arm Type
Active Comparator
Arm Description
Ibuprofen 200 mg daily, capsule
Arm Title
Isosorbide dinitrate and Ibuprofen
Arm Type
Experimental
Arm Description
Isosorbide dinitrate 20 mg daily and Ibuprofen 200 mg daily
Intervention Type
Drug
Intervention Name(s)
Isosorbide Dinitrate
Other Intervention Name(s)
Diniket 10 mg
Intervention Description
Isosorbide Dinitrate 10 mgx2, daily, capsules
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Other Intervention Name(s)
Antalgil 200 mg
Intervention Description
Ibuprofen 200 mg daily, capsules
Intervention Type
Other
Intervention Name(s)
Ibuprofen and Isosorbide Dinitrate combination
Other Intervention Name(s)
Antalgil 200 mg and Diniket 10 mg
Intervention Description
Ibuprofen 200 mg and Isosorbide Dinitrate 20 mg combination daily dose
Primary Outcome Measure Information:
Title
Pharmacokinetic parameter: AUC 0-12
Description
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
Time Frame
At period I, II and III with 7 days intervals between periods
Secondary Outcome Measure Information:
Title
C max
Description
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
Time Frame
At period I, II and III with 7 days intervals between periods
Title
T max
Description
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
Time Frame
At period I, II and III with 7 days intervals beteween periods
Title
Adverse Events
Description
Adverse Events registration At visit 2, visit 3 and visit 4
Time Frame
9 days
Title
Vital signs
Description
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
Time Frame
9 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
27 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emilio Clementi
Organizational Affiliation
Luigi Sacco Hospital - Phase I Department - Via G. B. Grassi 74 20157 Milano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Phase 1 Unit - Luigi Sacco Hospital
City
Milan
ZIP/Postal Code
20157
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
To Compare the Pharmacokinetics Profiles of ISO 20, IBU 200 and IBU Plus ISO Combinations 200 + 20
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