2011-355. Trials to Verify and Describe Clinical Benefit of Midodrine Hydrochloride; Establishment of Public Docket

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the opening of a public docket to provide a forum to facilitate communication regarding the conduct of clinical trials needed to verify and describe the clinical benefit of midodrine hydrochloride (HCl) when used to treat symptomatic orthostatic hypotension.

DATES:

Submit either electronic or written comments by July 11, 2011.

ADDRESSES:

Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT:

Wei Lu, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6196, Silver Spring, MD 20993-0002, e-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

FDA approved PROAMATINE (midodrine HCl) for marketing under its accelerated approval regulations, 21 CFR part 314, subpart H, on September 6, 1996, to treat patients with symptomatic orthostatic hypotension. Since that time, FDA has approved five generic versions of this product. Orthostatic hypotension is a condition in which patients are unable to maintain blood pressure in the upright position and become dizzy or faint upon standing. Subpart H allows approval of drugs to treat serious or life-threatening illnesses based on adequate and well-controlled clinical trials establishing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or based on a clinical endpoint other than survival or irreversible morbidity. Approval of PROAMATINE was based on trials demonstrating that PROAMATINE increased 1-minute standing systolic blood pressure, a surrogate marker considered likely to correspond to a clinical benefit, principally relief of symptoms of orthostatic hypotension and improved ability to perform life activities.

The subpart H regulations specify that approvals based upon surrogate endpoints are “subject to the requirement that the applicant study the drug further to verify and describe its clinical benefit” in postmarketing studies. The postmarketing study requirement for midodrine HCl was described in the new drug application (NDA) submission seeking its approval and referenced in the Agency's 1996 approval letter. In the time since PROAMATINE was approved, the NDA holder has sponsored clinical trials and information regarding the drug's efficacy has been published, but data submitted to the Agency have not verified the drug's clinical benefit to FDA's satisfaction. Accordingly, on August 16, 2010, FDA issued a notice of opportunity for a hearing (NOOH) on a proposal to withdraw approval of the NDA for midodrine HCl.

Although the NOOH process is proceeding on a separate track, FDA recognizes that existing and potential sponsors may wish to conduct the clinical trials needed to support continued marketing authorization of midodrine HCl. To assist sponsors in planning and designing such trials, we are placing in the docket a brief description of a recommended clinical trial design. We are also inviting interested parties to submit information to the docket such as any existing controlled studies that verify the clinical benefit of midodrine HCl when used to treat orthostatic hypotension. Physicians who treat orthostatic hypotension and patient organizations that would like to work with any sponsors of new clinical trials are invited to submit correspondence to the docket identifying themselves. We anticipate that any sponsor planning to conduct new clinical studies may contact interested physicians and organizations to solicit information and suitable volunteer test subjects.

The public docket is available for public review in the Division of Dockets Management (see ADDRESSES) between 9 a.m. and 4 p.m., Monday through Friday.

Dated: January 6, 2011.

David Dorsey,

Acting Deputy Commissioner for Policy, Planning and Budget.