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.