Tepilta® Versus Oxetacaine, Antacids and Placebo

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: January 2017

Detailed Description

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

Interventions

  • Drug: oxetacaine, aluminium and magnesium hydroxide
    • 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.
  • Drug: oxetacaine
    • 20mg/10ml oxetacaine. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.
  • Drug: magnesium and aluminium hydroxide
    • 196mg/10ml magnesium hydroxide, 582mg/10ml aluminium hydroxide. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.
  • Other: Vehicle
    • Placebo suspension for oral intake 3-6 times per day for a maximum of 11 weeks.

Arms, Groups and Cohorts

  • Experimental: Tepilta®
  • Active Comparator: Oxetacaine
  • Active Comparator: Antacids
  • Placebo Comparator: Placebo

Clinical Trial Outcome Measures

Primary Measures

  • Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO).
    • Time Frame: up to 11 weeks

Secondary Measures

  • ASPO: WHO analgesic pain ladder
    • Time Frame: up to 11 weeks
    • ASPO = Additional systemic pain medication for oesophagitis
  • Pain intensity recorded on NRS with scores 0-10
    • Time Frame: up to 11 weeks
    • NRS = Numeric Rating Scale
  • Swallowing disorder recorded on NRS with scores 0-10
    • Time Frame: up to 11 weeks
    • NRS = Numeric Rating Scale
  • Adapted CTCAE grade
    • Time Frame: up to 11 weeks
    • 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.
  • Incidence of artificial nutrition due to radiation-induced oesophagitis
    • Time Frame: up to 11 weeks
  • Incidence of interruptions of radiation therapy due to radiation-induced oesophagitis
    • Time Frame: up to 11 weeks
  • Duration of pain medication intake after the end of Radiation Therapy
    • Time Frame: up to 11 weeks
  • Loss of body weight
    • Time Frame: up to 11 weeks

Participating in This Clinical Trial

Inclusion Criteria

1. Male or female ≥ 18 years. 2. Score = 0 on NRS for oesophageal pain. 3. 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. 4. Duration of RT 5 to 8 weeks. 5. 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). 6. First radiation in the intended radiation area. 7. Written informed consent. Randomisation criteria: 8. Appearance of oesophageal pain as follows: Score ≥ 2 on Numeric Rating Scale (NRS) for pain during main daily meals is reached at least once. 9. At least 20 Gy of the dose of radiation therapy in oesophageal area remaining. 10. Oesophageal symptoms of grade ≤ 2a according to the adapted Common Terminology Criteria for Adverse Events CTCAE. Exclusion Criteria:

1. History of allergic reaction to the study medication or its excipients (i.e. aluminium or magnesium hydroxide, oxetacaine, any other ingredient of study medication). 2. Pregnancy, breast-feeding or planned pregnancy during the study. 3. Known hypermagnesaemia. 4. Known hypophosphataemia. 5. Clinically significant obstipation, as judged by the investigator. 6. Acute appendicitis. 7. Total intended radiation dose at lips and the anterior oral cavity > 60% of total intended radiation dose at the swallowing process (pharynx, oesophagus). 8. Hyper-fractionated RT. 9. Intended naso-gastral tubes. 10. Primary tumour of the cranial base, brain, oral cavity, lips, naso-pharynx, para-nasal sinuses. 11. Known bone metastases. 12. Reflux oesophagitis 3 months prior to the study. 13. Continuous systemic pain treatment at the beginning of RT. Systemic pain medication for oesophagitis prior to randomisation must not be taken. 14. Concomitant treatment with tetracyclines, cinolone derivatives (ciprofloxacin, ofloxacin, enoxacin, norfloxacin), cheno-desoxycholic acid, sodium fluoride, local anaesthetics (other than those used as study medication). 15. Patients relying on levothyroxine after resection of thyroid carcinoma being hypothyroid and patients relying on levothyroxine due to other reasons not being euthyroid. 16. Artificial nutrition at the beginning of radiation. 17. Drug (licit and illicit) or alcohol abuse which would interfere with the patient's proper completion of the study. 18. Exposure to an investigational product within the last 4 weeks, simultaneous exposure to another investigational product. 19. Lack of ability or willingness to give informed consent. 20. Anticipated non-availability for study visits / procedures. 21. Lack of ability or willingness to keep patient's diary. 22. Lack of willingness to have personal study related data collected, archived or transmitted according to the protocol. 23. Vulnerable subjects.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • MEDA Pharma GmbH & Co. KG
  • Collaborator
    • Trium Analysis Online GmbH
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Frank Bruns, Dr. med., Principal Investigator, Hannover Medical School
    • Ursula Petzold, PhD, Study Chair, MEDA Pharma GmbH & Co. KG

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