The US Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for Teva Pharmaceutical Industries' hydrocodone bitartrate extended-release (ER) tablets formulated with Teva’s proprietary abuse deterrence technology (CEP-33237). CEP-33237 is an investigational, 12-hour, acetaminophen-free, formulation of extended-release hydrocodone for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
"Teva is committed to developing innovative approaches to helping advance responsible pain management and is pleased the FDA is moving forward in its consideration of CEP-33237,” says Michael Hayden, MD, president of global R&D and chief scientific officer at Teva. "With positive results from Human Abuse Liability studies in the two most common routes of hydrocodone abuse, CEP-33237 with potential abuse deterrence properties, represents a positive step towards responsible pain management.”
The NDA filing is supported by a clinical programme that evaluated the safety and efficacy of CEP-33237, as well as the abuse potential of CEP-33237 via the oral and intranasal routes of abuse in Human Abuse Liability (HAL) studies:
Results from the phase III clinical programme for CEP-33237 showed significant improvement in the treatment of patients’ chronic low back pain as measured by both weekly average Worst Pain Intensity (WPI) and weekly Average Pain Intensity (API) scores.
In the oral HAL study in nondependent, recreational opioid users, abuse potential was significantly lower for finely crushed CEP-33237 than for immediate-release (IR) hydrocodone powder based on peak at-the-moment drug liking. Overall drug liking was also significantly lower for finely crushed CEP-33237 compared to IR hydrocodone.
The intranasal HAL study found that in nondependent, recreational opioid users, abuse potential for finely milled intranasal CEP-33237 was significantly lower based on peak at-the-moment drug liking than for intranasal IR hydrocodone powder and finely milled intranasal Zohydro ER (hydrocodone bitartrate) extended-release capsules [C-II] as commercially available at the time the study was conducted. Overall drug liking was also significantly lower for finely crushed CEP-33237 compared to IR hydrocodone and Zohydro ER.
CEP-33237 demonstrated a safety profile in the phase III study that is consistent with the known safety profile of hydrocodone and other opioid analgesic therapies. Adverse events reported in five per cent or more of hydrocodone-treated patients during either the titration or double-blind treatment periods included: nausea, constipation, vomiting, headache, somnolence and dizziness.
“The impact of living with chronic pain can be devastating, affecting many aspects of daily life,” said Richard Malamut, MD, vice president of global clinical development and therapeutic area head of pain at Teva. “If approved, CEP-33237 will provide an important treatment option for people living with chronic pain and healthcare professionals who care for them.”