NanoBUP™ Buprenorphine/Naloxone Capsule

Buprenorphine, used in the treatment of moderate and severe acute and chronic pain as well as opioid addiction, is a partial agonist at the μ-opioid receptor and produces a sub-maximal response compared to that of a full agonist. The ceiling effect on respiratory depression provides a greater margin of safety in comparison to other full agonist opioids. Buprenorphine HCl is also an antagonist at the κ-opioid receptor. Naloxone is a drug used to counter the effects of opioid overdose and, similar to Suboxone®, in NanoBUP™ is intended to render the product less abusable by deterring intravenous injection. Naloxone HCl is a competitive antagonist with high affinity for μ-opioid receptors in the CNS. Naloxone HCl also has an antagonist action, though with a lower affinity, at κ- and δ-opioid receptors.
NanoBUP™ buprenorphine / naloxone capsule is being developed for the treatment of opioid dependence. The NanoBUP™ oral swallowed capsule is presented as a fixed dose combination of buprenorphine HCl / naloxone HCl, at a ratio of 4:1 with respect to the free bases, similar in dose and ratio to the Suboxone® 2.0mg buprenorphine / 0.5mg naloxone sublingual tablet (NDA# 20-733, approved 10/8/02, Reckitt Benckiser Pharmaceuticals Inc.). Preclinical animal studies support that NanoBUP™ immediate-release formulation allows buprenorphine to be absorbed from the upper gastrointestinal tract upon ingestion, offering a less invasive route of administration (swallowed vs. sublingual) and potentially resolving the absorption variability of Suboxone®.
An initial Phase Ia trial is planned as a single-dose, open-label, 1-period, 1-treatment, safety study in which six (6) healthy adult subjects will receive one (1) single-dose oral administration of buprenorphine HCl / naloxone HCl dosed as two (2) capsules, each capsule containing 2mg/0.5mg of buprenorphine / naloxone for a total of 4mg/1mg of buprenorphine / naloxone, following an overnight fast of at least ten (10) hours.

Nanotherapeutics has entered a manufacturing and supply agreement for opioid-based active pharmaceutical ingredients with Noramco, Inc., The agreement includes the supply of buprenorphine hydrochloride, one of the active ingredients in NanoBUP™. Noramco, Inc. is a leading supplier of opioid-based active ingredients for generic and branded pharmaceutical products.