A Clinical Study to Compare BupiZenge With Lidocaine for Pain Due to Oral Mucositis in Patients With Head and Neck Cancer. (BEAM-Pain)

A Randomized, Open-label, Phase III Trial to Assess the Efficacy and Safety of BupiZenge Compared to Lidocaine for Pain Associated With Oral Mucositis in Head and Neck Cancer

Most patients who receive radiation therapy for head and neck cancer develop painful sores in the mouth called oral mucositis. For many of them, these sores are severe and result in debilitating pain. The sores usually start in the third week of radiation and last aboutfive weeks, often continuing for two weeks after treatment ends. Current pain treatments, for instance lidocaine solution, only give short-lasting pain relief.

BupiZenge is a lozenge that dissolves slowly in the mouth and contains bupivacaine. Bupivacaine is a long-acting pain-relieving medicine and has been safely used for many years for both children and adults, and its safety profile is well understood. The BupiZenge lozenge is designed to give longer and more reliable pain relief for patients with mucositis in their mouth.

This study will check if BupiZenge works better to reduce pain than lidocaine, and if better pain control improves quality of life and reduces the need for strong pain medicines like opioids.

The main goal is to see how much mouth pain decreases after taking BupiZenge compared to lidocaine. This is measured by asking the patients to rate their pain score on a scale from 0 (no pain) to 10 (worst possible pain). This is done at different time-points, from before the dose until three hours after dose on the last day of radiotherapy.

The study will include 150 adults, both women and men, aged 18 to 80 years, who have head and neck cancer and are scheduled to receive radiotherapy, with or without chemotherapy. These patients will be randomly assigned to one of the treatment groups. The first is BupiZenge, which is a lozenge containing bupivacaine, which dissolves slowly in the mouth. The second is lidocaine, which is a liquid solution for use in the mouth that you gurgle or swish around in the mouth.

The study begins with a combined screening and run-in period that can last up to five weeks. During radiotherapy, patients record their mouth pain each day using a number scale from 0 (no pain) to 10 (worst possible pain). If the pain score is at least 4 (moderate pain) and they have developed mucositis in the mouth within 5 weeks, patients are randomly assigned to receive either BupiZenge or Lidocaine.

Treatment continues at least until radiotherapy is completed. If the patient has pain and mouth sores, and the treatment is working well, it may continue after radiotherapy ends, but only until the sores heal or for a maximum of six weeks in total, whichever occurs first. After treatment ends, there is a 30-day follow-up period.

Study Overview

• Status: Not yet recruiting
• Conditions: Oral Mucositis; Head & Neck Cancer
• Intervention / Treatment: Drug: BupiZenge 25 mg; Drug: Lidocaine viscous 2%

Detailed Description

Pharmacokinetic (PK) parameters of bupivacaine in plasma will be evaluated in a sub-trial including participants randomized to the BupiZenge treatment arm.

Approximately 15 participants (no more than 25), across all designated PK sites, will participate in a PK sub-trial. Blood samples will be collected before the dose and at scheduled time points up to three hours after the dose for PK evaluation. Samples will be analyzed by a central laboratory, and results will be reported to the Sponsor or Sponsor's designee during the course of the trial. Overall, the PK sub-group represents a targeted, ethical, and efficient approach to verify systemic safety parameters for BupiZenge in the intended patient population.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chief Executive Officer (CEO); Phone Number: +468311420; Email: info@oncozenge.se

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, Copenhagen University Hospital
  • Herlev, Denmark, 2730
    • Herlev Hospital
  • Næstved, Denmark, 4700
    • Næstved Hospital
• Germany
  • Cologne, Germany, 50937
    • University Hospital Cologne (Universitätsklinikum Köln AöR)
  • Frankfurt am Main, Germany, 60596
    • University Hospital Frankfurt (AöR)
  • Freiburg im Breisgau, Germany, 79106
    • Medical Center - University Of Freiburg
  • Kiel, Germany, 24105
    • University Hospital Schleswig-Holstein (AöR)
  • Tübingen, Germany, 72076
    • University Hospital Tübingen (AöR)
• Norway
  • Bergen, Norway, 5021
    • Helse Bergen HF
  • Oslo, Norway, 0379
    • Oslo University Hospital HF
• Sweden
  • Stockholm, Sweden, SE-17164
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 a highly effective contraceptive measure or practice total sexual abstinence from the time of giving informed consent until at least 24 hours after last dose of IMP.

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:

  1. AST/ALT > 3 × upper limit of normal (ULN) or bilirubin > 1.5 × ULN (unless related to Gilbert's syndrome)
  2. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BupiZenge; Bupivacaine hydrochloride, 25 mg lozenge	Drug: BupiZenge 25 mg; 1 lozenge as needed. Do not chew or swallow. Dosing interval: ≥ 3 h. Max dose/24 h: 8 lozenges.
Active Comparator: Lidocaine; Lidocaine hydrochloride oral topical solution, 20 mg/mL	Drug: Lidocaine viscous 2%; 10-15 mL as needed. Hold the solution in the mouth and distribute evenly, then either spit out or swallow. Dosing interval ≥ 3 h. Max dose/24 h: 120 mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total pain reduction in oral cavity pain over 3 hours after taking study treatment on the last day of radiotherapy	Oral pain will be measured using a 0-10 numerical rating scale (0 = no pain, 10 = worst possible pain). Participants will rate their pain before taking the study treatment and at several time points after dosing. These measurements will be combined to assess how pain changes over time after treatment and to compare BupiZenge with lidocaine.	From before to 3 hours after dose, on the last day of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total pain reduction in oral cavity pain over 3 hours after taking study treatment	Oral pain will be measured using a 0-10 numerical rating scale (0 = no pain, 10 = worst possible pain). Participants will rate their pain before taking the study treatment and at several time points after dosing. These measurements will be combined to assess how pain changes over time after treatment and to compare BupiZenge with lidocaine.	From before dose to 3 hours after dose, on Day 1 and during Weeks 1 to 3
Proportion of patients with meaningful pain reduction over 3 hours after taking study treatment	Oral pain will be measured using a 0-10 numerical rating scale (0 = no pain, 10 = worst possible pain). Patients who achieve at least a 30% reduction in their overall pain will be considered responders. Pain scores will be collected before dosing and at several time points after dosing, and combined to assess the overall change in pain over time. The proportion of responders will be compared between BupiZenge and lidocaine.	From before dose to 3 hours after dose, on the last day of radiotherapy and during Weeks 1 to 3
Change in oral cavity pain 15 minutes after taking study treatment	Oral pain will be measured using a 0-10 numerical rating scale (0 = no pain, 10 = worst possible pain). Weekly pain changes will be compared between BupiZenge and lidocaine.	From before dose to 15 minutes after dose during the week before end of radiotherapy and during Weeks 1 to 3 after radiotherapy
Change in oral cavity pain 60 minutes after taking study treatment	Oral pain will be measured using a 0-10 numerical rating scale (0 = no pain, 10 = worst possible pain). Weekly pain changes will be compared between BupiZenge and lidocaine.	From before dose to 60 minutes after dose during the week before end of radiotherapy and during Weeks 1 to 3 after radiotherapy
Change in oral cavity pain from Day 1 before dose to later pre-dose assessments	Oral pain will be measured using a 0-10 numerical rating scale. Weekly changes in pain before dose will be compared between BupiZenge and lidocaine.	From before dose (Day 1) to before dose during the week before end of radiotherapy and during Weeks 1 to 3 after radiotherapy
Safety as measured frequency and severity of adverse events	Adverse events and serious adverse events will be collected and graded using CTCAE v6.	From signature of informed consent up to 30 days after treatment discontinuation
Change from baseline in hematology laboratory parameters.	Hematology laboratory parameters (hemoglobin, hematocrit, red blood cell count, white blood cell count with differential count and platelet count) will be summarized by visit using descriptive statistics, including changes from baseline. The frequency of values below, within, or above the reference range will be summarized by visit.	From informed consent to 30 days after treatment discontinuation.
Change from baseline in chemistry laboratory parameters.	Chemistry laboratory parameters (CRP, Albumin, ALT, AST, ALP, Bilirubin (total and conjugated), Calcium, Potassium, Sodium, Creatinine, hCG (if applicable)) will be summarized by visit using descriptive statistics, including changes from baseline. The frequency of values below, within, or above the reference range will be summarized by visit.	From informed consent to 30 days after treatment discontinuation.
Changes from baseline in body weight	Body weight will be summarized by visit using descriptive statistics, including changes from baseline. Changes in weight will be expressed as both absolute (kg) and relative (%) changes.	From signature of informed consent up to 30 days after treatment discontinuation
Changes from baseline in blood pressure.	Blood pressure will be summarized by visit using descriptive statistics, including changes from baseline.	From signature of informed consent up to 30 days after treatment discontinuation
Changes from baseline in heart rate.	Heart rate will be summarized by visit using descriptive statistics, including changes from baseline.	From signature of informed consent up to 30 days after treatment discontinuation
Changes from baseline in body temperature .	Body temperature will be summarized by visit using descriptive statistics, including changes from baseline.	From signature of informed consent up to 30 days after treatment discontinuation
Changes from baseline in respiratory rate.	Respiratory rate will be summarized by visit using descriptive statistics, including changes from baseline.	From signature of informed consent up to 30 days after treatment discontinuation
Tolerability as measured by dose modifications due to adverse events	The number of participants who require dose modifications of study treatment due to adverse events will be recorded.	From signature of informed consent up to 30 days after treatment discontinuation
Adverse Events related to local tolerability in the oral cavity, as assessed by CTCAE v6.0, will be summarized.	Local tolerability in the oral cavity will be assessed and the result will be summarized by visit using descriptive statistics. The investigator will inspect the oral mucosa or tongue where the lozenge was placed to assess for any visible irritation or other local reaction. Any observed irritation will be documented and reported as an AE.	From Week 2 up to Week 5.
Oral intake of opioids during the treatment period with concomitant BupiZenge/lidocaine treatment and radiotherapy comparing BupiZenge with lidocaine.	Use of opioid pain medication will be recorded and converted to oral morphine milligram equivalents (MME) per day. Opioid use will be compared between BupiZenge and lidocaine.	From randomization up to Week 5.
Time (days) to start of opioid medication during radiotherapy comparing BupiZenge with lidocaine	The number of days from randomization until the participant first starts opioid pain medication will be recorded and compared between BupiZenge and lidocaine.	From randomization up to Week 5.
Change in Modified Oral Mucositis Daily Questionnaire (mOMDQ) Total Score	Participants will complete the mOMDQ. Changes in the total score will be compared between BupiZenge and lidocaine.	From randomization up to Week 5.
Quality-of-life measured as change from baseline using RAND SF-36 questionnaire	Participants will complete the Quality-of-life questionnaire RAND SF-36. The Physical Component Summary (PCS) score will be calculated according to the RAND SF-36 scoring algorithm. Change from baseline in PCS score will be summarized using descriptive statistics.	From randomization up to Week 5.
Progression of oral mucositis from WHO Grade 2 to Grade 3 or higher	The proportion of participants with worsening of oral mucositis, from WHO Grade 2 to Grade 3 or higher, during radiotherapy will be assessed and compared between BupiZenge and lidocaine.	From randomization up to Week 5.
Maximum Plasma Concentration [Cmax] of bupivaccaine in plasma.	Blood samples will be collected from approximately 15 of the participants receiving BupiZenge treatment.	Before the dose up to three hours after the dose. Two occasions per participant during the six-week treatment period
Maximum Plasma Concentration [Cmax] of bupivaccaine in plasma.	Blood samples will be collected from approximately 15 of the participants receiving BupiZenge treatment. Plasma concentrations of bupivacaine will be summarized descriptively at each time-point and visit they are assessed.	Before the dose up to three hours after the dose. Two occasions per participant during the six-week treatment period
Time to maximum Plasma Concentration [Tmax] of bupivaccaine in plasma.	Blood samples will be collected from approximately 15 of the participants receiving BupiZenge treatment. Plasma concentrations of bupivacaine will be summarized descriptively at each time-point and visit they are assessed. Tmax will be summarized using median and range.	Before the dose up to three hours after the dose. Two occasions per participant during the six-week treatment period
Area under the plasma concentration-time curve from time zero to 3 hours after dose (AUC0-3h)	Blood samples will be collected from approximately 15 of the participants receiving BupiZenge treatment. AUC 0-3h will be summarized descriptively at each time-point and visit they are assessed.	Before the dose up to three hours after the dose. Two occasions per participant during the six-week treatment period
Health Resource Utilization Questionnaire (HRUQ) Total Score at 30 days after treatment	Participants will complete the HRUQ. The questionnaire is structure for collecting healthcare utilization data in clinical research and health-economic evaluation. The total score will be compared between BupiZenge and lidocaine.	Assessed 30 days after end of treatment
Change in Work Productivity and Activity Impairment (WPAI) Total Score from baseline to 30 days after treatment	Participants will complete the WPAI questionnaire. Change from baseline in total score will be summarized using descriptive statistics.	From screening to 30 days after end of treatment

Collaborators and Investigators

• Sponsor: OncoZenge AB
• Collaborators: LINK Medical Research AB
• Investigators: Study Director: Chief Medical Officer (CMO), OncoZenge AB

Study record dates

Study Major Dates

• Study Start (Estimated): June 25, 2026
• Primary Completion (Estimated): December 23, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: June 17, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Stomatitis
• Other Study ID Numbers: BZ003; 2025-524386-24-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to company policy and to protect participant privacy and confidential information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No