PDF Clinical Considerations in the Evaluation of the Safety and ...

Clinical Considerations in the

Evaluation of the Safety and Effectiveness of Hydexor

Timothy Jiang, MD, PhD Clinical Reviewer

Division of Anesthesia, Analgesia, and Addiction Products (DAAAP) CDER, FDA

Agenda

? Introduction ? Study Population ? Safety evaluation with a focus on CNS

adverse events (AEs) ? Indication

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Introduction

? Hydexor is a fixed-dose combination product that contains the analgesics hydrocodone and acetaminophen in combination with the antiemetic promethazine

? Sponsor's proposed indication

? "The short-term management of acute pain severe enough to require an opioid analgesic while preventing and reducing opioidinduced nausea and vomiting (OINV). Hydexor is indicated when alternative treatments for pain are inadequate."

? Novel Indication

? Hydexor has not been formulated with features intended to deter abuse, similar to all other hydrocodone/acetaminophen products currently available on the market

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Phase 3 Study Population

? The Sponsor conducted two Phase 3 efficacy and safety studies intended to support the use of Hydexor for the proposed indication

? One in dental pain (Study CLCT-002 ) and one in post-bunionectomy pain (study CLCT-003)

? Both studies enrolled a population of patients that were anticipated to be prone to opioid-induced nausea/vomiting

? Assessment was based on the results of the Nausea Prone Questionnaire (NPQ) +/- a hydrocodone challenge ? Based on these assessments, patients were classified as ? "Likely Nausea-Prone" ? "Possible Nausea-Prone"

? Additionally, the protocol allowed investigators to enroll up to 10% of patients who did not meet the predefined nausea-prone criteria but were thought to be nausea-prone based on clinical judgment

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Nausea-Prone Results ? Randomized

Patients

Study CLCT-002 ? Randomized Patients

Study CLCT-003 ? Randomized Patients

Category Likely Nausea-Prone Possible Nausea-Prone Investigator Discretion Total

N (%) 367 (79%) 78 (17%)

21 (5%) 466

Category Likely Nausea-Prone Possible Nausea-Prone Investigator Discretion Total

N (%) 383 (69%) 132 (24%)

37 (7%) 552

FDA Statistical Review by Dr. James Travis

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