This funding opportunity announcement (FOA) aims to fund applications designed to assess the clinical value of adjuncts prescribed to chronic pain patients together with opioid analgesics. Adjuncts of interest are either approved by the U.S. Food and Drug Administration (FDA) or have previously been studied as an investigational new drug. Studies with adjuncts of interest should be focused on enhancing analgesia rather than on reducing an adverse effect. A secondary purpose is to increase awareness among opioid prescribers of the potential value of adjunctive therapies by focused data dissemination.
It is hoped that by increasing availability of data describing the use of opioid adjuncts, their use will increase and levels of opioids needed for analgesia will diminish. Reductions in the dosage of opioids prescribed would improve the quality of life of chronic pain patients by reducing opioid-associated adverse effects and lowering the risk of addiction development.
Studies should examine clinical populations and address whether a proposed adjunct can reduce the dose of opioid required for analgesia compared with opioid monotherapy. Applications will be evaluated on the feasibility, scientific rigor, and likely value of the proposed outcomes of randomized control trials (RCTs) to study opioid-adjunct combinations. In addition, the investigators should describe their plan to disseminate the study results. This plan will be evaluated with a view to how effectively the study results will be communicated to the types of healthcare providers who typically prescribe opioids to the chronic pain population under examination.
The purpose of this FOA is to examine adjunctive therapies to reduce the need for opioids in chronic pain patients. Therefore, in the patient group under investigation the pain syndrome should chronologically precede opioid exposure and the opioids should be prescribed as a treatment for the pain.
In the population proposed to be studied, the subjects should be etiologically homogenous and symptomatically well defined. Examples of such chronic pain populations in which opioids often are prescribed include patients with radicular cervical pain, metastatic bone pain, or peripheral neuropathies.
Studies should use an RCT design to examine opioid and adjunct formulations that are either typically used in the outpatient chronic pain population under study or are feasible for daily use in that population. For example, a formulation that requires once-a-day oral dosing is likely to be of much higher programmatic interest than a formulation requiring multiple daily dosing or intrathecal administration. Adjuncts to be examined should preferably be FDA approved, examples of which would include pregabalin, duloxetine, or dronabinol. However, agents that currently are being (or previously have been) studied as investigational new drugs (for example, Sativex/Nabiximols) also will be considered.
Submissions were accepted beginning September 5 and letters of intent are due 30 days before applications are due. For more information about this funding opportunity, visit the NIH grants page.
Development of Opioid and Adjuvant Fixed Combination Dosage Forms for the Treatment of Chronic Pain with Reduced Addiction Potential (R41/R42)
This funding opportunity announcement seeks small business organizations to develop opioid and adjuvant drug combinations within a single dosage form for treatment of a pain condition. The drug combination should provide improved analgesia when compared with the same dose (morphine equivalents) of opioid monotherapy. Such dosage forms should minimize opioid exposure while optimizing analgesia to reduce risk of addiction and limit severity of other opiate adverse effects.
When designing this new product, investigators should consider FDA guidance (21 CFR 300.50) and address the following issues. Both of the agents contained in the proposed new product should currently have at least one existing FDA-approved indication, as well as some existing clinical evidence to support the use of the chosen adjuvant-opioid combination and a reasonable expectation that the combination will present minimal drug-drug interaction concerns. The application should emphasize available evidence that the chosen drugs and doses in the combination will allow a substantial patient population to gain sufficient analgesic value from the contained opioid dose while the adjuvant dose remains within a safe and effective "therapeutic window." One example of a potentially viable adjuvant is gabapentin, a drug known to reduce neuropathic pain and to which patients typically exhibit no more than mild adverse effects. Gabapentin typically does not induce substantial drug interactions because it is eliminated as parent drug by renal excretion and does not bind extensively to blood proteins.
The adjuvant should be chosen for a capacity to increase overall analgesia, rather than an ability to reduce opioid adverse effects. For example, inclusion of a poorly absorbed opioid receptor antagonist, with the intent of reducing constipation, would not be considered of high programmatic interest.
The combination dosage form proposed by the application should provide sustained relief when it is the only analgesic used and is administered no more than three times in a 24-hour period. The formulation should be such that a patient with reasonable mobility is able to self-administer the drug (e.g., oral dosage form).
The application should propose late-stage drug development–oriented studies that significantly drive the project toward an ultimate aim of a New Drug Application [505(b)(1 or 2)] or Abbreviated New Drug Application [505(j)] for the treatment of a long-term pain condition.
Studies planned for Phase 1 of the project should focus on issues that concern the feasibility of the project. The exact nature of such studies will differ depending on the proposed drug combination project.
Studies that might be appropriate for Phase 1 STTR applications include, but are not limited to
- development of a formulation that safely delivers the desired amount of both agents over an appropriate dosing interval
- preclinical studies demonstrating additive or synergistic analgesia with the opioid-adjuvant combination
- studies to provide data for an Investigational New Drug (IND) submission, such as short-term stability studies
- pre-IND consultations with an FDA project management group and development of the IND documentation.
Examples of projects appropriate for Phase 2 of an STTR award might include
- pharmacokinetic absorption and disposition studies to demonstrate the bioequivalence between approved dosage forms and the proposed product
- proof of concept clinical studies. Appropriate outcome measures might aim to detect and distinguish value added by an opioid adjunctive therapy, whether due to improved analgesia or reduced required opioid dosage.
Submissions were accepted beginning March 5 and letters of intent are due 30 days before applications are due. For more information about this funding opportunity, visit the NIH grants page.
This funding opportunity announcement (FOA) is issued by the National Institute of Neurological Disorders and Stroke (NINDS) in conjunction with the National Institutes of Health (NIH) Pain Consortium. It solicits R01 grant applications from institutions and organizations to perform innovative research that will elucidate the mechanisms underlying migraine; expand our current knowledge of the role of genetic, physiological, biopsychosocial, and environmental influences in migraine susceptibility and progression; and explore new therapeutic targets and therapies for acute migraine management and longer-term prevention.
The National Center for Complementary and Alternative Medicine (NCCAM) is interested in research that would elucidate the mechanisms by which a given complementary or integrative health approach beneficially affects migraine, either as an acute intervention or prophylactically. For this FOA, complementary or integrative health approaches could include those within the “mind and body” domain but not in the “natural products” domain and would include, but are not limited to, meditation, mindfulness, yoga, tai chi, qi-gong, acupuncture, massage, and spinal manipulation. The primary outcomes for these studies should be focused directly on the mechanism(s), though it may be appropriate to have secondary outcomes that assess clinical outcomes. There should be sufficient prior data to indicate either efficacy or effectiveness of the proposed complementary or integrative health approach.
The National Institute for Dental and Craniofacial Research (NIDCR) is interested in the neurobiological mechanisms underlying migraine headache as they pertain to overlaps with pathophysiological mechanisms of chronic temporomandibular and other orofacial pain disorders. Research examining common genetic, environmental, neurobiological, and biobehavioral factors underlying the co-occurrence of these disorders is encouraged. NIDCR is interested in funding meritorious research that focuses on studies addressing the comorbidity of temporomandibular and other orofacial disorders and migraine headache.
NIDCR is interested in the development of diagnostic, interventional, and novel therapeutic tools for headache pain associated with a variety of communication disorders such as tinnitus, Meniere’s disease, odynophagia, and burning mouth syndrome. Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the program director or principal investigator (PD or PI) is invited to work with his or her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities always are encouraged to apply for NIH support.
Submissions will be accepted beginning May 5. For more information about this funding opportunity, visit the NIH grants page.