Tepilta® Versus Oxetacaine, Antacids and Placebo

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

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.

Study Overview

• Status: Terminated
• Conditions: Radiation-induced Oesophagitis
• Intervention / Treatment: Drug: oxetacaine, aluminium and magnesium hydroxide; Drug: oxetacaine; Drug: magnesium and aluminium hydroxide; Other: Vehicle

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Feldkirch, Austria, 6807
    • Landeskrankenhaus Feldkirch
  • Innsbruck, Austria, 6020
    • Universitätsklinik für Strahlentherapie-Radioonkologie
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen
  • Altötting, Germany, 84503
    • RADIO LOG Strahlentherapie Altötting
  • Bad Homburg, Germany
    • please contact Dr. Ingrid Schwienhorst/MEDA for details
  • Berlin, Germany, 12351
    • Vivantes Klinikum Neukölln
  • Berlin, Germany, 14050
    • Strahlenheilkunde Westend
  • Bielefeld, Germany, 33615
    • Franziskus Hospital
  • Bochum, Germany, 44791
    • Klinik für Hämatologie, Onkologie & Palliativmedizin
  • Bonn, Germany, 53177
    • Strahlentherapie Bonn-Rhein-Sieg
  • Braunschweig, Germany, 38114
    • Städtisches Klinikum Braunschweig GmbH
  • Coesfeld, Germany, 48653
    • Strahlentherapie Coesfeld
  • Dortmund, Germany, 44309
    • Knappschaftskrankenhaus Dortmund
  • Frankfurt (Oder), Germany, 15236
    • Klinikum Frankfurt (Oder) GmbH
  • Frankfurt am Main, Germany, 60488
    • Krankenhaus Nordwest Gmbh
  • Freising, Germany, 85354
    • Strahlentherapie - Freising
  • Gummersbach, Germany, 51643
    • Kreiskrankenhaus Gummersbach
  • Halle (Saale), Germany, 06110
    • Universitätsklinikum Halle (Saale)
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Herne, Germany, 44625
    • Kath. Krankenhaus Marienhospital
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig
  • Marburg, Germany, 35033
    • Klinik für Strahlentherapie und Radioonkologie
  • Mönchengladbach, Germany, 41063
    • Kliniken Maria Hilf GmbH
  • München, Germany, 81377
    • Klinikum der Universität München
  • München, Germany, 80804
    • Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum Schwabing
  • Osnabrück, Germany, 49076
    • Paracelsus-Klinik Osnabrück
  • Ostfildern, Germany, 73760
    • Paracelsus-Krankenhaus Ruit
  • Paderborn, Germany, 33098
    • Brüderkrankenhaus St. Josef
  • Potsdam, Germany, 14467
    • Klinikum Ernst von Bergmann
  • Recklinghausen, Germany, 45659
    • Prosperhospital Recklinghausen
  • Rostock, Germany, 18059
    • Universitätsklinikum Rostock AöR
  • Stuttgart, Germany, 70174
    • Klinik für Radioonkologie und Strahlentherapie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Vehicle; Placebo suspension for oral intake 3-6 times per day for a maximum of 11 weeks.
Experimental: Tepilta®	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.; Other Names: Tepilta®
Active Comparator: Oxetacaine	Drug: oxetacaine; 20mg/10ml oxetacaine. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.
Active Comparator: Antacids	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 Names: Antacids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: MEDA Pharma GmbH & Co. KG
• Collaborators: ICON plc; Clinipace Worldwide; Trium Analysis Online GmbH
• Investigators: Principal Investigator: Frank Bruns, Dr. med., Hannover Medical School; Study Chair: Ursula Petzold, PhD, MEDA Pharma GmbH & Co. KG

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: April 1, 2011
• First Submitted That Met QC Criteria: April 14, 2011
• First Posted (Estimate): April 18, 2011

Study Record Updates

• Last Update Posted (Actual): February 7, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Radiotherapy; Oesophageal pain; Combined radio-chemotherapy; Oesophageal symptoms
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Esophageal Diseases; Esophagitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Anesthetics, Local; Magnesium Hydroxide; Antacids; Aluminum Hydroxide; Oxethazaine
• Other Study ID Numbers: X-03030-3277; 2009-014441-93 (EudraCT Number)