Efficacy and Safety of Bupivacaine Hydrochloride Monohydrate versus Lidocaine Hydrochloride for the Management of Oral Mucositis-Associated Pain in Head and Neck Cancer Patients

Trial ID: 2025-524386-24-00
Protocol: BZ003
Sponsor: OncoZenge AB

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Diseases & Conditions

Stomatitis Head and neck cancer

Objectives

The primary objective of this study is to evaluate the efficacy of BupiZenge in reducing oral mucositis-related pain in patients with head and neck cancer. The secondary objectives include:

Assessment of patient-reported oral cavity pain in a home setting.
Evaluation of safety and tolerability.
Measurement of systemic opioid consumption following administration.
Evaluation of mouth and throat symptoms and their functional impact.
Assessment of health-related quality of life.
Comparison of disease severity progression using the WHO OM grade.
Investigation of pharmacokinetic characteristics in a subset of participants.
Evaluation of healthcare resource utilization.
Assessment of work productivity and activity impairment.

Participants

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with head and neck cancer, specifically squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or nasopharynx. Participants must be between 18 and 80 years of age and possess an Eastern Cooperative Oncology Group performance status of 0-2. Eligible individuals are scheduled to undergo intensity-modulated radiation therapy with curative intent. The study aims to evaluate the effect of BupiZenge on oral mucositis and patient-reported oral cavity pain. Female participants of childbearing potential are required to utilize effective contraception.

Plans and Procedures

This Phase III, randomized, open-label trial is designed to evaluate the efficacy and safety of BupiZenge compared to lidocaine for the management of pain associated with oral mucositis in patients with head and neck cancer. The study methodology involves comparing the test product, a 200 mg bupivacaine hydrochloride monohydrate lozenge, against a comparator, lidocaine hydrochloride oral solution. The primary endpoint is the total reduction in pain from baseline, measured by the Numerical Rating Scale (NRS) as the area under the curve (AUC) of pain intensity from pre-dose to 3 hours post-dose on the final day of radiotherapy. Secondary endpoints include the proportion of responders, changes in pain intensity at specific post-dose intervals, safety assessments via Common Terminology Criteria for Adverse Events (CTCAE), and pharmacokinetic parameters. The clinical procedure includes a screening visit to confirm eligibility based on criteria such as a pathologically confirmed diagnosis of squamous cell carcinoma and an ECOG Performance Status of 0-2. Following randomization, participants undergo treatment during radiotherapy and subsequent follow-up visits to assess pain reduction and safety at weekly intervals through week 3 after radiotherapy. Participant involvement is centered around the radiotherapy course and the subsequent three-week follow-up period.

Treatment

The experimental medication, BupiZenge, consists of bupivacaine hydrochloride monohydrate. This substance is administered in a lozenge pharmaceutical form at a dosage of 200 mg via oromucosal use.

The comparator treatment is Lidocaine, containing lidocaine hydrochloride. This medication is provided as an oral solution for oromucosal use at a dose of 120 ml.

Efficacy

The primary efficacy endpoint is the total pain reduction from baseline, expressed as the area under the curve (AUC) of patient-reported oral cavity pain intensity from pre-dose to 3 hours post-dose. This measurement is obtained using the Numerical Rating Scale (NRS) at the last day of radiotherapy.

Secondary efficacy assessments include:

Total pain reduction from baseline, expressed as AUC of patient-reported oral cavity pain intensity from pre-dose to 3 hours post-dose, measured by the NRS at day 1 and at each week from week 1 to week 3 of treatment.
Proportion of responders, defined as a 30% reduction in pain NRS AUC0-3h compared to baseline at the last day of radiotherapy and at each week from week 1 to week 3.
Change from pre-dose in oral cavity pain intensity at 15 minutes and 60 minutes post-dose, measured by NRS and reported by the patient at home, during the week preceding the end of radiotherapy and at each week from week 1 to week 3 after radiotherapy.
Change from pre-dose (day 1) in oral cavity pain intensity to pre-dose NRS reported at home.
Oral consumption of opioids quantified as oral morphine milligram equivalents (MME) per day.
Time in days to the initiation of opioid medication from the day of randomization.
Change from baseline to the last day of radiotherapy in the mOMDQ Total Score.
Change from baseline to the last day of radiotherapy in the RAND SF-36 Physical Component Summary (PCS) score.
Proportion of participants progressing from WHO Grade 2 to WHO Grade 3 or higher during the treatment period with concomitant radiotherapy.
Pharmacokinetic (PK) parameters in plasma, including time vs concentration profiles, AUC0-3h, Cmax, and Tmax.
HRUQ Total Score assessed at 30 days post-treatment.
WPAI Total Score assessed as change from baseline to 30 days post-treatment.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Participant must provide signed written informed consent prior to trial participation and must be willing and able to comply with all requirements and restrictions of the trial.
Male or female aged ≥ 18 on the day of consent and ≤ 80 on the first day of dosing
Pathologically confirmed diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or nasopharynx.
About to start IMRT with curative intent with daily fractions of 2.0 Gy to 2.2 Gy to a cumulative intended dose of at least 60 Gy and a maximum of 72 Gy. Proton therapy given at equivalent biological doses is allowed.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
Female participants of childbearing potential (WOCBP) must agree to use at least an acceptable effective method of contraception or practice total abstinence from the time of giving informed consent until at least 24 hours after last dose of IMP.

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Exclusion Criteria

Participation in another investigational interventional clinical trial within 3 months prior to first dosing, or for a longer period if required by local regulations, or within 5 half-lives of the investigational agent taken (whichever is longer). An exception is studies where patients are randomized to different radiotherapy settings, e.g. participation in DAHANCA 35 is allowed.
Previous radiation therapy to the head and/or neck area.
Pre-existing OM, active herpes simplex virus (HSV) infection, or untreated or uncontrolled oral candidiasis.
Receiving high-dose (> 15 mg per day prednisolone), corticosteroids (for any indication).
Known allergy or intolerance to bupivacaine, lidocaine, or any of the excipients in the products.
Significant cardiac disease such as AV block II-III or requiring treatment with antiarrhythmic drugs in class III (e.g., amiodarone).
Inability to eat or drink, or dependence on an enteral feeding tube (percutaneous endoscopic gastrostomy [PEG] or nasogastric tube) for any reason.
Moderate/severe liver or kidney disease defined as: AST/ALT > 3 × upper limit of normal (ULN) or bilirubin > 1.5 × ULN (unless related to Gilbert’s syndrome), glomerular filtration rate (GFR) < 30 mL/min/1.73 m2
Known diagnosis of epilepsy.
Known phenylketonuria (PKU).
Pregnancy or breastfeeding.
Any condition or circumstance—based on the investigator’s assessment—that could increase risk to the participant, confound trial results, or interfere with compliance / participation (including inability or unwillingness to follow trial procedures, or any clinically significant physical or psychiatric condition).