[Federal Register Volume 65, Number 25 (Monday, February 7, 2000)]
[Notices]
[Pages 5874-5875]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-2628]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Cooperative Research and Development Agreement (CRADA) To 
Undertake Research and Development of a Corticotropin Releasing Factor 
(CRF) Antagonist(s) for the Treatment of Cocaine Dependence

AGENCY: National Institute of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: The National Institute on Drug Abuse (NIDA), a component of 
the National Institutes of Health, is seeking proposals from potential 
collaborators for a Cooperative Research and Development Agreement 
(CRADA) to test, by scientific means meeting U.S. Food and Drug 
Administration (FDA) standards, the hypothesis that Corticotropin 
Releasing Factor (CRF) antagonists may be useful in the treatment of 
cocaine dependence. NIDA will consider proposals from all qualified 
entities and will, subject to negotiation of a mutually agreed upon 
research plan, provide substantial in kind clinical and preclinical 
resources with the understanding that the CRADA collaborator will be 
free to utilize data from the CRADA to pursue regulatory filings in the 
U.S. and abroad. Subject to negotiation of details in a mutually agreed 
upon research plan, NIDA will provide the CRADA collaborator with 
access to its preclinical development components and clinical trials 
contractual network. No NIH funding may be provided to a collaborator 
under a CRADA, therefore the collaborator will bear the financial and 
organizational costs of meeting its obligations under the research 
plan. It is NIDA's intention to provide, at a minimum, clinical trials 
services sufficient to permit, subject to FDA approval, research and 
development up to and including Phase II hypothesis testing trials. 
Assuming demonstration of safety and efficacy at the conclusion of 
Phase II trials and subject to negotiation, NIDA will consider 
undertaking Phase III trials sufficient to permit collaborator to seek 
a U.S. New Drug Approval (NDA).

DATES: NIDA will consider all proposals received within 90 days of the 
date of publication of this notice. This notice is active until May 8, 
2000.

ADDRESSES: Questions about this notice may be addressed to Mr. Lee 
Cummings (301-443-1143) or Dr. Frank Vocci (301-443-2711) at the 
following address: Division of Treatment Research and Development, 
National Institute on Drug Abuse, 6001 Executive Boulevard, MSC 9551, 
Bethesda, Maryland 20892-9551.

SUPPLEMENTARY INFORMATION: There is mounting evidence that drugs of 
abuse effect the brain systems mediating the stress response. Evidence 
suggests that withdrawal syndromes associated with chronic use of drugs 
of abuse results in elevations of Corticotropin Releasing Factor (CFR) 
levels. The effects of chronic opiate and cocaine abuse in human 
subjects have been studied. Investigators have reported derangements of 
the stress response, even long after cessation of drug use. Taken 
together, these results would suggest a role of the CRF system in acute 
and, possibly, protracted abstinence. A role of stress in relapse to 
drugs of abuse is strongly suspected.
    Stress has been shown to modify the intake of drugs of abuse in 
preclinical studies of drug self-administration. The effect of stress 
to increase drug intake has been shown for opiates and cocaine. 
Moreover, the effects of stress can be mimicked by CRF administration 
and inhibited by CRF antagonists. The inhibitory effect of CRF 
antagonists on stress-induced increases in drug-taking behavior is 
impressively robust. Hence,

[[Page 5875]]

further study of the modulation of stress responses by CRF antagonists 
in drug dependent and formerly dependent subjects and the possible 
relationship to reduction of drug use or prevention of relapse is a 
high priority for NIDA.\1\ NIDA does not currently own or have access 
to a CRF antagonist with which to undertake this line of research and 
development. To this end, NIDA is seeking collaborations with 
pharmaceutical partners to evaluate CRF antagonists in drug dependent 
and formerly drug dependent subjects. NIDA is seeking to enter into a 
Cooperative Research and Development Agreement (CRADA) with a 
pharmaceutical company or its license, the purpose of which would be to 
assess the effects of CRF antagonists in drug dependent populations. 
NIDA is willing to provide both intellectual expertise and preclinical 
and clinical support in a collaboration. While NIDA would prefer to 
enter into a CRADA with a company or licensee that is already in 
clinical testing phase with a CRF antagonist, it would also entertain 
collaborations involving drug candidates in the preclinical stage of 
testing. NIDA's Medications Development Program possesses the capacity 
to perform pharmacological and toxicological testing, pharmacokinetics, 
dosage form development and clinical testing from Phase I through Phase 
III testing and is willing to apply these capacities in the assessment 
of a CRF antagonist.
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    \1\ A review of the scientific literature on stress, drugs of 
abuse, and relapse to drug use is available upon request.
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    Selection factors of importance of NIDA include:
    (1) It is mandatory that the collaborator have proprietary rights 
to the CRF antagonist sufficient to permit research and commercial 
development for the intended field of use, i.e., treatment of cocaine 
dependence. In the event the collaborator does not own the CRF 
antagonist, collaborator must provide appropriate documentation of a 
commercialization license to the field of use sufficient to permit the 
CRADA to proceed. Collaborator must be able to supply dosage forms of a 
CRF antagonist made to FDA Good Manufacturing Practices (GMP) standards 
sufficient to permit each stage of research and development to proceed.
    (2) NIDA will consider the amount of research and development 
documentation and experience already in the collaborator's possession. 
NIDA will sign appropriate confidential disclosure agreements in order 
to review proprietary and unpublished data. While NIDA will consider 
all proposals, it will give a higher priority to proposals that can 
document a more advanced level of development with the proposed CRF 
antagonist.
    (3) NIDA will consider the amount and type of research and 
development resources the collaborator proposes to undertake as part of 
a proposed CRADA.
    (4) NIDA will consider the background, experience, and expertise in 
medications development of the proposed collaborator.

    Dated: February 1, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-2628 Filed 2-4-00; 8:45 am]
BILLING CODE 4140-01-M