[Federal Register Volume 83, Number 2 (Wednesday, January 3, 2018)]
[Notices]
[Pages 383-384]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-28337]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-D-6759]


Establishing Effectiveness for Drugs Intended To Treat Male 
Hypogonadotropic Hypogonadism Attributed to Non-Structural Disorders; 
Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled 
``Establishing Effectiveness for Drugs Intended to Treat Male 
Hypogonadotropic Hypogonadism Attributed to Non-Structural Disorders.'' 
This draft guidance provides key design considerations, including 
recommendations for patient enrollment criteria and efficacy endpoints, 
for clinical trials to establish effectiveness for drugs intended to 
treat male hypogonadotropic hypogonadism associated with obesity and 
other conditions that do not cause intrinsic damage to the hypothalamus 
or pituitary gland. This draft guidance is consistent with 
recommendations FDA received at the December 2014 advisory committee 
meeting on the appropriate indicated population for testosterone 
replacement therapy, and the December 2016 advisory committee meeting 
on hypogonadotropic hypogonadism.

DATES: Submit either electronic or written comments on the draft 
guidance by March 5, 2018 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and

[[Page 384]]

identified, as confidential, if submitted as detailed in 
``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2017-D-6759 for ``Establishing Effectiveness for Drugs Intended to 
Treat Male Hypogonadotropic Hypogonadism Attributed to Non-Structural 
Disorders.'' Received comments will be placed in the docket and, except 
for those submitted as ``Confidential Submissions,'' publicly viewable 
at https://www.regulations.gov or at the Dockets Management Staff 
office between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one 
self-addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Jeannie Roule, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5332, Silver Spring, MD 20993-0002, 301-
796-3993.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Establishing Effectiveness for Drugs Intended to Treat Male 
Hypogonadotropic Hypogonadism Attributed to Non-Structural Disorders.'' 
This draft guidance is intended to assist sponsors in designing drug 
development programs to demonstrate effectiveness of drugs intended to 
treat male hypogonadotropic hypogonadism associated with obesity and 
other conditions that do not cause intrinsic damage to the hypothalamus 
or pituitary gland.
    Male hypogonadism is characterized by serum testosterone 
concentrations below the lower limit of the normal range for young, 
healthy men with associated symptoms (e.g., reduced libido) or signs 
(e.g., loss of muscle mass with reduced muscle strength). Some men who 
have had normal puberty and sexual development are subsequently 
diagnosed with hypogonadotropic hypogonadism associated with obesity or 
other acquired conditions in the absence of intrinsic damage to the 
hypothalamus or pituitary. Although these men have serum testosterone 
concentrations below the lower limit of the normal range for young, 
healthy men, the associated symptoms often experienced in this 
population (e.g., low energy, depressed mood) are nonspecific and 
cannot definitively be attributed to the low testosterone 
concentrations. In addition, it is unclear whether these testosterone 
concentrations--in the absence of intrinsic damage to the hypothalamus 
and pituitary gland--are inappropriately low and whether increasing 
testosterone concentrations in these men confers clinical benefit.
    For these reasons, serum testosterone is not a validated surrogate 
endpoint for establishing efficacy in these patients, and sponsors 
would need to show that an increase in serum testosterone translates 
into improvement in how patients feel, function, or survive.
    This draft guidance addresses the following topics in establishing 
effectiveness of drugs for this population:

 Identification of patients for inclusion in clinical trials 
and
 Efficacy endpoints.

    This draft guidance is consistent with recommendations FDA received 
at the December 2014 advisory committee meeting on the appropriate 
indicated population for testosterone replacement therapy, and the 
December 2016 advisory committee meeting on hypogonadotropic 
hypogonadism.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on establishing 
effectiveness for drugs intended to treat male hypogonadotropic 
hypogonadism attributed to non-structural disorders. It does not 
establish any rights for any person and is not binding on FDA or the 
public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations. This guidance 
is not subject to Executive Order 12866.

II. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.regulations.gov.

    Dated: December 27, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-28337 Filed 1-2-18; 8:45 am]
BILLING CODE 4164-01-P


