Tepilta® Versus Oxetacaine, Antacids and Placebo

NCT01336530 | Terminated Phase 3 DMC

• 2 other identifiers: X-03030-32772009-014441-93
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 32

Brief Summary

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.

Conditions

Radiation-induced Oesophagitis

Keywords

Oesophageal pain; Radiotherapy; Combined radio-chemotherapy; Oesophageal symptoms

Outcome Measures

Primary Outcomes (1)

• Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO).

  up to 11 weeks

Secondary Outcomes (8)

• ASPO: WHO analgesic pain ladder

  up to 11 weeks

• Pain intensity recorded on NRS with scores 0-10

  up to 11 weeks

• Swallowing disorder recorded on NRS with scores 0-10

  up to 11 weeks

• Adapted CTCAE grade

  up to 11 weeks

• Incidence of artificial nutrition due to radiation-induced oesophagitis

  up to 11 weeks

Study Arms (4)

Tepilta®

EXPERIMENTAL

Drug: oxetacaine, aluminium and magnesium hydroxide

Oxetacaine

ACTIVE COMPARATOR

Drug: oxetacaine

Antacids

ACTIVE COMPARATOR

Drug: magnesium and aluminium hydroxide

Placebo

PLACEBO COMPARATOR

Other: Vehicle

Interventions

oxetacaine, aluminium and magnesium hydroxide DRUG

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.

Also known as: Tepilta®

Tepilta®

oxetacaine DRUG

20mg/10ml oxetacaine. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.

Oxetacaine

magnesium and aluminium hydroxide DRUG

196mg/10ml magnesium hydroxide, 582mg/10ml aluminium hydroxide. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.

Also known as: Antacids

Antacids

Vehicle OTHER

Placebo suspension for oral intake 3-6 times per day for a maximum of 11 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• MEDA Pharma GmbH & Co. KG: lead
• Trium Analysis Online GmbH: collaborator
• ICON plc: collaborator
• Clinipace Worldwide: collaborator

Study Sites (32)

Landeskrankenhaus Feldkirch

Feldkirch, 6807, Austria

Location

Universitätsklinik für Strahlentherapie-Radioonkologie

Innsbruck, 6020, Austria

Location

Universitätsklinikum Aachen

Aachen, 52074, Germany

Location

RADIO LOG Strahlentherapie Altötting

Altötting, 84503, Germany

Location

please contact Dr. Ingrid Schwienhorst/MEDA for details

Bad Homburg, Germany

Location

VIVANTES Klinikum Neukölln

Berlin, 12351, Germany

Location

Strahlenheilkunde Westend

Berlin, 14050, Germany

Location

Franziskus Hospital

Bielefeld, 33615, Germany

Location

Klinik für Hämatologie, Onkologie & Palliativmedizin

Bochum, 44791, Germany

Location

Strahlentherapie Bonn-Rhein-Sieg

Bonn, 53177, Germany

Location

Städtisches Klinikum Braunschweig GmbH

Braunschweig, 38114, Germany

Location

Strahlentherapie Coesfeld

Coesfeld, 48653, Germany

Location

Knappschaftskrankenhaus Dortmund

Dortmund, 44309, Germany

Location

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), 15236, Germany

Location

Krankenhaus Nordwest GmbH

Frankfurt am Main, 60488, Germany

Location

Strahlentherapie - Freising

Freising, 85354, Germany

Location

Kreiskrankenhaus Gummersbach

Gummersbach, 51643, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, 06110, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Kath. Krankenhaus Marienhospital

Herne, 44625, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinik für Strahlentherapie und Radioonkologie

Marburg, 35033, Germany

Location

Kliniken Maria Hilf GmbH

Mönchengladbach, 41063, Germany

Location

Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum Schwabing

München, 80804, Germany

Location

Klinikum der Universität München

München, 81377, Germany

Location

Paracelsus-Klinik Osnabrück

Osnabrück, 49076, Germany

Location

Paracelsus-Krankenhaus Ruit

Ostfildern, 73760, Germany

Location

Brüderkrankenhaus St. Josef

Paderborn, 33098, Germany

Location

Klinikum Ernst von Bergmann

Potsdam, 14467, Germany

Location

Prosperhospital Recklinghausen

Recklinghausen, 45659, Germany

Location

Universitätsklinikum Rostock AöR

Rostock, 18059, Germany

Location

Klinik für Radioonkologie und Strahlentherapie

Stuttgart, 70174, Germany

Location

MeSH Terms

Interventions

oxethazaine; Aluminum; Magnesium Hydroxide; Magnesium; Aluminum Hydroxide; Antacids

Intervention Hierarchy (Ancestors)

Metals, Light; Elements; Inorganic Chemicals; Metals; Hydroxides; Alkalies; Anions; Ions; Electrolytes; Magnesium Compounds; Metals, Alkaline Earth; Aluminum Compounds; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Gastrointestinal Agents; Therapeutic Uses

Study Officials

• Frank Bruns, Dr. med.

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

• Ursula Petzold, PhD

  MEDA Pharma GmbH & Co. KG

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2011
• First Posted: April 18, 2011
• Study Start: April 1, 2011
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: February 7, 2022

Record last verified: 2017-02

Locations

AU (2); DE (30)