Tepilta® Versus Oxetacaine, Antacids and Placebo

Study Overview
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Brief Summary
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This is a randomised, double-blind, placebo-controlled, therapeutic confirmatory multicentre trial with 4 parallel treatment groups. The design is adaptive group-sequential with two interim analyses, possible sample size re-estimation after the first or second interim analysis and drop-the-loser approach. The study design was primarily chosen to show superior efficacy of Tepilta® compared to the single components and to placebo. Evaluation of safety is a secondary objective.

Detailed Description
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Tepilta® Suspension is indicated for treatment of pain in the upper digestive system induced by radiation therapy, in particular for radiation-induced oesophagitis.

Official Title
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Clinical Trial to Assess the Efficacy of Fixed Combination Product Tepilta® in the Treatment of Radiation-induced Oesophagitis Compared to Its Active Ingredients Oxetacaine and Antacids, and to Placebo

Conditions
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Radiation-induced Oesophagitis

Intervention / Treatment
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* Drug: oxetacaine, aluminium and magnesium hydroxide
* Drug: oxetacaine
* Drug: magnesium and aluminium hydroxide
* Other: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years. Score = 0 on NRS for oesophageal pain. Radiotherapy (RT) or combined radio-chemotherapy (RCT) of a solid tumour in head/neck/thorax region. A minimum length of 5 cm of the oesophagus must be included in high-dose radiation field. Duration of RT 5 to 8 weeks. Single radiation dosage of fractionated RT 1.8 to 2.0 Gy/day, of intensity-modulated RT (IMRT) 1.5 to 2.3 Gy/day, each for 5 days a week (single frequency deviations are allowed presuming that intended duration of RT remains 5 to 8 weeks). First radiation in the intended radiation area. Written informed consent. Randomisation criteria: Appearance of oesophageal pain as follows: Score ≥ 2 on Numeric Rating Scale (NRS) for pain during main daily meals is reached at least once. At least 20 Gy of the dose of radiation therapy in oesophageal area remaining. Oesophageal symptoms of grade ≤ 2a according to the adapted Common Terminology Criteria for Adverse Events CTCAE. Exclusion Criteria: History of allergic reaction to the study medication or its excipients (i.e. aluminium or magnesium hydroxide, oxetacaine, any other ingredient of study medication). Pregnancy, breast-feeding or planned pregnancy during the study. Known hypermagnesaemia. Known hypophosphataemia. Clinically significant obstipation, as judged by the investigator. Acute appendicitis. Total intended radiation dose at lips and the anterior oral cavity > 60% of total intended radiation dose at the swallowing process (pharynx, oesophagus). Hyper-fractionated RT. Intended naso-gastral tubes. Primary tumour of the cranial base, brain, oral cavity, lips, naso-pharynx, para-nasal sinuses. Known bone metastases. Reflux oesophagitis 3 months prior to the study. Continuous systemic pain treatment at the beginning of RT. Systemic pain medication for oesophagitis prior to randomisation must not be taken. Concomitant treatment with tetracyclines, cinolone derivatives (ciprofloxacin, ofloxacin, enoxacin, norfloxacin), cheno-desoxycholic acid, sodium fluoride, local anaesthetics (other than those used as study medication). Patients relying on levothyroxine after resection of thyroid carcinoma being hypothyroid and patients relying on levothyroxine due to other reasons not being euthyroid. Artificial nutrition at the beginning of radiation. Drug (licit and illicit) or alcohol abuse which would interfere with the patient's proper completion of the study. Exposure to an investigational product within the last 4 weeks, simultaneous exposure to another investigational product. Lack of ability or willingness to give informed consent. Anticipated non-availability for study visits / procedures. Lack of ability or willingness to keep patient's diary. Lack of willingness to have personal study related data collected, archived or transmitted according to the protocol. Vulnerable subjects.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tepilta®<br> | Drug: oxetacaine, aluminium and magnesium hydroxide<br>* 20mg/10ml oxetacaine, 196mg/10ml magnesium hydroxide, 582mg/10ml aluminium hydroxide. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.<br>* Other names: Tepilta®;|
| Active Comparator: Oxetacaine<br> | Drug: oxetacaine<br>* 20mg/10ml oxetacaine. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.<br>|
| Active Comparator: Antacids<br> | Drug: magnesium and aluminium hydroxide<br>* 196mg/10ml magnesium hydroxide, 582mg/10ml aluminium hydroxide. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.<br>* Other names: Antacids;|
| Placebo Comparator: Placebo<br> | Other: Vehicle<br>* Placebo suspension for oral intake 3-6 times per day for a maximum of 11 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO). |  | up to 11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASPO: WHO analgesic pain ladder | ASPO = Additional systemic pain medication for oesophagitis | up to 11 weeks | 
| Pain intensity recorded on NRS with scores 0-10 | NRS = Numeric Rating Scale | up to 11 weeks | 
| Swallowing disorder recorded on NRS with scores 0-10 | NRS = Numeric Rating Scale | up to 11 weeks | 
| Adapted CTCAE grade | CTCAE = Common Terminology Criteria for Adverse Events Severity of oesophageal symptoms will be evaluated by the investigator according to an adapted CTCAE grading system. In contrast to the original CTCAE classification the adapted version foreseen to be used in this study distinguishes level 2a and 2b. 2a = symptomatic; altered eating/swallowing; oral supplements indicated; requiring predominantly pureed or soft diet, 2b = symptomatic; altered eating/swallowing; oral supplements indicated; requiring predominantly liquid diet. | up to 11 weeks | 
| Incidence of artificial nutrition due to radiation-induced oesophagitis |  | up to 11 weeks | 
| Incidence of interruptions of radiation therapy due to radiation-induced oesophagitis |  | up to 11 weeks | 
| Duration of pain medication intake after the end of Radiation Therapy |  | up to 11 weeks | 
| Loss of body weight |  | up to 11 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oesophageal pain, Radiotherapy, Combined radio-chemotherapy, Oesophageal symptoms