Isosorbide dinitrate plus Ibuprofen

Randomized double-blind placebo-controlled trial of flavocoxid in Duchenne muscular dystrophy

Dr. Emilio Clementi and Dr. Grazia D’Angelo
L Sacco University Hospital, Milan, Italy

Saturday 6th February 2010

The proposal concerns a double blind placebo controlled trial to assess the tolerability and safety of treatment with isosorbide dinitrate plus ibuprofen in dystrophic patients. The trial is based on preclinical evidence obtained in mdx and sarcoglycan-null dystrophic mice and preliminary observation from an open pilot clinical study.

Professor Rudolf Korinthenberg was the lead reviewer and guided the meeting discussions and generation of the TACT recommendations report to the applicant.

In summary, based on the preclinical data with the combination of these drugs in mdx mice, TACT recommended further dose ranging and PK studies in mice and in pilot human studies to define if an effective level of drug is likely without unacceptable side effects.  As proposed by the applicants, TACT believed that a trial of these agents in the non-ambulant DMD population could be feasible provided certain aspects of the trial design, as outlined in the report to the applicant, were addressed. From a regulatory perspective involvement of EMA and FDA at an early stage including orphan drug designation was recommended, as was the approach of treating these compounds as "two products simultaneously".

“In general, we have had a very good impression and we do think it is a very valuable instrument to help clinicians and scientists to design sensible clinical trials in muscular dystrophy. TACT should be highly publicised and possibly put into some sort of official agreement with the regulatory agencies.”

“The form is self explanatory and easy to fill in…. The idea of a direct contact with the committee before the actual delivery of the final recommendations we think is a great idea, and definitely to maintain, exactly in the same format as we experienced in Rome.”

“Concerning the review: …good comments and very helpful ……focused and straight.”

“Limitation …. now that we have your suggestions we design a trial the best way we think; but apparently we do not have any further contact with the committee to see how the new version looks like to them. We think instead that a follow up would be valuable.”

“A second good thing would be to envisage a way to create a path putting in contact the trial proponent with funding charities/agencies. This would be important as the trials you are reviewing will mostly be non-sponsored ones. This would also enhance the appeal of applying to TACT.”

Dr. Emilio Clementi and Dr. Grazia D’Angelo.

12 Apr 2017