[Federal Register Volume 76, Number 7 (Tuesday, January 11, 2011)]
[Notices]
[Pages 1620-1621]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-355]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-N-0637]


Trials to Verify and Describe Clinical Benefit of Midodrine 
Hydrochloride; Establishment of Public Docket

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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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: [email protected].

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

[[Page 1621]]

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.
[FR Doc. 2011-355 Filed 1-10-11; 8:45 am]
BILLING CODE 4160-01-P