Tepilta® Versus Oxetacaine, Antacids and Placebo

Sponsor

MEDA Pharma GmbH & Co. KG (Industry)

Overall Status

Terminated

CT.gov ID

NCT01336530

Collaborator

Trium Analysis Online GmbH (Industry), ICON plc (Industry), Clinipace Worldwide (Industry)

Enrollment

Locations

Arms

69.1

Actual Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, 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

Actual Study Start Date :

Apr 1, 2011

Actual Primary Completion Date :

Jan 1, 2017

Actual Study Completion Date :

Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
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
Placebo Comparator: Placebo	Other: Vehicle Placebo suspension for oral intake 3-6 times per day for a maximum of 11 weeks.

Outcome Measures

Primary Outcome Measures

Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO). [up to 11 weeks]

Secondary Outcome Measures

ASPO: WHO analgesic pain ladder [up to 11 weeks]
ASPO = Additional systemic pain medication for oesophagitis
Pain intensity recorded on NRS with scores 0-10 [up to 11 weeks]
NRS = Numeric Rating Scale
Swallowing disorder recorded on NRS with scores 0-10 [up to 11 weeks]
NRS = Numeric Rating Scale
Adapted CTCAE grade [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 [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Landeskrankenhaus Feldkirch	Feldkirch	Austria	6807
2	Universitätsklinik für Strahlentherapie-Radioonkologie	Innsbruck	Austria	6020
3	Universitätsklinikum Aachen	Aachen	Germany	52074
4	RADIO LOG Strahlentherapie Altötting	Altötting	Germany	84503
5	please contact Dr. Ingrid Schwienhorst/MEDA for details	Bad Homburg	Germany
6	VIVANTES Klinikum Neukölln	Berlin	Germany	12351
7	Strahlenheilkunde Westend	Berlin	Germany	14050
8	Franziskus Hospital	Bielefeld	Germany	33615
9	Klinik für Hämatologie, Onkologie & Palliativmedizin	Bochum	Germany	44791
10	Strahlentherapie Bonn-Rhein-Sieg	Bonn	Germany	53177
11	Städtisches Klinikum Braunschweig GmbH	Braunschweig	Germany	38114
12	Strahlentherapie Coesfeld	Coesfeld	Germany	48653
13	Knappschaftskrankenhaus Dortmund	Dortmund	Germany	44309
14	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)	Germany	15236
15	Krankenhaus Nordwest GmbH	Frankfurt am Main	Germany	60488
16	Strahlentherapie - Freising	Freising	Germany	85354
17	Kreiskrankenhaus Gummersbach	Gummersbach	Germany	51643
18	Universitätsklinikum Halle (Saale)	Halle (Saale)	Germany	06110
19	Medizinische Hochschule Hannover	Hannover	Germany	30625
20	Kath. Krankenhaus Marienhospital	Herne	Germany	44625
21	Universitätsklinikum Leipzig	Leipzig	Germany	04103
22	Klinik für Strahlentherapie und Radioonkologie	Marburg	Germany	35033
23	Kliniken Maria Hilf GmbH	Mönchengladbach	Germany	41063
24	Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum Schwabing	München	Germany	80804
25	Klinikum der Universität München	München	Germany	81377
26	Paracelsus-Klinik Osnabrück	Osnabrück	Germany	49076
27	Paracelsus-Krankenhaus Ruit	Ostfildern	Germany	73760
28	Brüderkrankenhaus St. Josef	Paderborn	Germany	33098
29	Klinikum Ernst von Bergmann	Potsdam	Germany	14467
30	Prosperhospital Recklinghausen	Recklinghausen	Germany	45659
31	Universitätsklinikum Rostock AöR	Rostock	Germany	18059
32	Klinik für Radioonkologie und Strahlentherapie	Stuttgart	Germany	70174