Tepilta® Versus Oxetacaine, Antacids and Placebo

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by MEDA Pharma GmbH & Co. KG
Sponsor:
Collaborators:
Trium Analysis Online GmbH
ICON plc
Clinipace Worldwide
Information provided by (Responsible Party):
MEDA Pharma GmbH & Co. KG
ClinicalTrials.gov Identifier:
NCT01336530
First received: April 1, 2011
Last updated: April 26, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Radiation-induced Oesophagitis
Drug: oxetacaine, aluminium and magnesium hydroxide
Drug: oxetacaine
Drug: magnesium and aluminium hydroxide
Other: Vehicle
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by MEDA Pharma GmbH & Co. KG:

Primary Outcome Measures:
  • Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO). [ Time Frame: up to 11 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ASPO: WHO analgesic pain ladder [ Time Frame: up to 11 weeks ] [ Designated as safety issue: No ]
    ASPO = Additional systemic pain medication for oesophagitis

  • Pain intensity recorded on NRS with scores 0-10 [ Time Frame: up to 11 weeks ] [ Designated as safety issue: No ]
    NRS = Numeric Rating Scale

  • Swallowing disorder recorded on NRS with scores 0-10 [ Time Frame: up to 11 weeks ] [ Designated as safety issue: No ]
    NRS = Numeric Rating Scale

  • Adapted CTCAE grade [ Time Frame: up to 11 weeks ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
  • Incidence of interruptions of radiation therapy due to radiation-induced oesophagitis [ Time Frame: up to 11 weeks ] [ Designated as safety issue: No ]
  • Duration of pain medication intake after the end of Radiation Therapy [ Time Frame: up to 11 weeks ] [ Designated as safety issue: No ]
  • Loss of body weight [ Time Frame: up to 11 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 810
Study Start Date: April 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Antacids
Placebo Comparator: Placebo Other: Vehicle
Placebo suspension for oral intake 3-6 times per day for a maximum of 11 weeks.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01336530

Contacts
Contact: Ingrid Schwienhorst, Dr. +49 6172 888 ext 01 ingrid.schwienhorst@medapharma.de

Locations
Austria
Landeskrankenhaus Feldkirch Terminated
Feldkirch, Austria, 6807
Universitätsklinik für Strahlentherapie-Radioonkologie Terminated
Innsbruck, Austria, 6020
Germany
Universitätsklinikum Aachen Completed
Aachen, Germany, 52074
RADIO LOG Strahlentherapie Altötting Completed
Altötting, Germany, 84503
Strahlenheilkunde Westend Recruiting
Berlin, Germany, 14050
Contact: Andrej Stupavsky, Dr. med.       a.stupavsky@drk-kliniken-berlin.de   
Principal Investigator: Andrej Stupavsky, Dr. med.         
Praxis - Zentrum für Strahlentherapie und Radioonkologie Terminated
Berlin, Germany, 12627
VIVANTES Klinikum Neukölln Terminated
Berlin, Germany, 12351
Franziskus Hospital Terminated
Bielefeld, Germany, 33615
Klinik für Hämatologie, Onkologie & Palliativmedizin Recruiting
Bochum, Germany, 44791
Contact: contact sponsor cf. sponsor       ingrid.schwienhorst@medapharma.de   
Strahlentherapie Bonn-Rhein-Sieg Terminated
Bonn, Germany, 53177
Städtisches Klinikum Braunschweig GmbH Terminated
Braunschweig, Germany, 38114
Strahlentherapie Coesfeld Terminated
Coesfeld, Germany, 48653
Knappschaftskrankenhaus Dortmund Recruiting
Dortmund, Germany, 44309
Contact: Heidemarie Tonscheidt, Dr. med.       tonscheidt.strahlentherapie@radiologie-do.de   
Principal Investigator: Heidemarie Tonscheid, Dr. med.         
Klinikum Frankfurt (Oder) GmbH Terminated
Frankfurt (Oder), Germany, 15236
Krankenhaus Nordwest GmbH Suspended
Frankfurt am Main, Germany, 60488
Strahlentherapie - Freising Terminated
Freising, Germany, 85354
Kreiskrankenhaus Gummersbach Terminated
Gummersbach, Germany, 51643
Universitätsklinikum Halle (Saale) Recruiting
Halle (Saale), Germany, 06110
Contact: Thomas Reese, Dr. med.       thomas.reese@medizin.uni-halle.de   
Principal Investigator: Thomas Reese, Dr. med.         
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Frank Bruns, Dr. med       Bruns.Frank@mh-hannover.de   
Principal Investigator: Frank Bruns, Dr. med.         
Kath. Krankenhaus Marienhospital Recruiting
Herne, Germany, 44625
Contact: Irenäus A. Adamietz, Prof. Dr.       irenaeus.a.adamietz@ruhr-uni-bochum.de   
Principal Investigator: Irenäus A. Adamietz, Prof. Dr.         
Universitätsklinikum Leipzig Recruiting
Leipzig, Germany, 04103
Contact: Kirsten Papsdorf, Dr. med.       Kirsten.Papsdorf@medizin.uni-leipzig.de   
Principal Investigator: Kisten Papsdorf, Dr. med.         
Klinik für Strahlentherapie und Radioonkologie Recruiting
Marburg, Germany, 35033
Contact: contact sponsor cf. sponsor       ingrid.schwienhorst@medapharma.de   
Kliniken Maria Hilf GmbH Completed
Mönchengladbach, Germany, 41063
Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum Schwabing Terminated
München, Germany, 80804
Klinikum der Universität München Terminated
München, Germany, 81377
Paracelsus-Klinik Osnabrück Completed
Osnabrück, Germany, 49076
Paracelsus-Krankenhaus Ruit Terminated
Ostfildern, Germany, 73760
Brüderkrankenhaus St. Josef Terminated
Paderborn, Germany, 33098
Klinikum Ernst von Bergmann Recruiting
Potsdam, Germany, 14467
Contact: contact sponsor cf. sponsor       ingrid.schwienhorst@medapharma.de   
Prosperhospital Recklinghausen Recruiting
Recklinghausen, Germany, 45659
Contact: Dorothea Riesenbeck, Dr. med.       D.Riesenbeck@servitia.de   
Principal Investigator: Dorothea Riesenbeck, Dr. med.         
Universitätsklinikum Rostock AöR Terminated
Rostock, Germany, 18059
Klinik für Radioonkologie und Strahlentherapie Recruiting
Stuttgart, Germany, 70174
Contact: contact sponsor cf. sponsor       ingrid.schwienhorst@medapharma.de   
Sponsors and Collaborators
MEDA Pharma GmbH & Co. KG
Trium Analysis Online GmbH
ICON plc
Clinipace Worldwide
Investigators
Principal Investigator: Frank Bruns, Dr. med. Hannover Medical School
Study Chair: Ursula Petzold, PhD MEDA Pharma GmbH & Co. KG
  More Information

Responsible Party: MEDA Pharma GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT01336530     History of Changes
Other Study ID Numbers: X-03030-3277  2009-014441-93 
Study First Received: April 1, 2011
Last Updated: April 26, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Austria: Agency for Health and Food Safety

Keywords provided by MEDA Pharma GmbH & Co. KG:
Oesophageal pain
Radiotherapy
Combined radio-chemotherapy
Oesophageal symptoms

Additional relevant MeSH terms:
Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Aluminum Hydroxide
Antacids
Magnesium Hydroxide
Anti-Ulcer Agents
Oxethazaine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 28, 2016