Trial Outcomes & Findings for A Comparative Investigation of Standard Of Care (SOC) and Episil® in Combination Versus SOC Alone on Oral Mucositis (NCT NCT01684566)

Results Overview

Summary of WHO (World Health Organisation) Oral Toxicity Scores Area under the curve (AUC) over the 28-Day Period ITT Populations. A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

116 participants

Primary outcome timeframe

28 days

Results posted on

2016-03-14

Participant Flow

Participant milestones

Participant milestones
Measure	Standard-Of-Care + Episil(R) Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Overall Study STARTED	60	56
Overall Study Treated (ITT)	57	52
Overall Study COMPLETED	44	49
Overall Study NOT COMPLETED	16	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Comparative Investigation of Standard Of Care (SOC) and Episil® in Combination Versus SOC Alone on Oral Mucositis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard-Of-Care + Episil(R) n=57 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=52 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Total n=109 Participants Total of all reporting groups
Age, Continuous	46.4 years STANDARD_DEVIATION 15.21 • n=5 Participants	49.0 years STANDARD_DEVIATION 14.82 • n=7 Participants	47.6 years STANDARD_DEVIATION 15.01 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	15 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	37 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	56 Participants n=5 Participants	51 Participants n=7 Participants	107 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Sweden	11 participants n=5 Participants	9 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Israel	23 participants n=5 Participants	23 participants n=7 Participants	46 participants n=5 Participants
Region of Enrollment Poland	13 participants n=5 Participants	13 participants n=7 Participants	26 participants n=5 Participants
Region of Enrollment Germany	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Intention to treat (ITT) and Last observation carried forward (LOCF)

Summary of WHO (World Health Organisation) Oral Toxicity Scores Area under the curve (AUC) over the 28-Day Period ITT Populations. A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=57 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=52 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population	0.63 score Standard Deviation 0.702	0.56 score Standard Deviation 0.589

PRIMARY outcome

Timeframe: 28 days

Population: Per Protocol (PP) without Last observation carried over(LOCF)

Summary of WHO (World Health Organisation) Oral Toxicity Scores AUC Over the 28-Day Period Per protocol population. A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=37 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=49 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population	0.39 score Standard Deviation 0.402	0.56 score Standard Deviation 0.587

SECONDARY outcome

Timeframe: 28 days

Population: Intention to treat (ITT)

Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organization) oral toxicity scale grade 0-4. A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=57 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=52 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Occurrence of Oral Mucositis	44 participants	40 participants

SECONDARY outcome

Timeframe: 28 days

Population: ITT (Intention to treat). There were13 patients in the episil +SOC group and 12 patients in the SOC group who had no data for duration of oral mucositis

Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis was graded according to WHO 5 Point grading scale on a daily basis. Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=44 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=40 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Duration of Oral Mucositis, Intention to Treat Population	9.5 Days Standard Deviation 6.85	10.7 Days Standard Deviation 6.03

SECONDARY outcome

Timeframe: 28 days

Population: Intention to treat(ITT) OMDQ AUC over time. Not all patients reported data from OMDQ therefore there is lower number of patients in this analysis.

OMDQ (Oral Mucositis Daily Questionnaire) scale was used to measure Overall Mouth and Throat Soreness This was scored from 0=no soreness to 10=worst possible soreness.

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=41 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=36 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Oral Mucositis Daily Questionnaire (OMDQ)	2.59 units on a scale Standard Deviation 1.619	2.64 units on a scale Standard Deviation 1.539

SECONDARY outcome

Timeframe: 28 days

Population: Intention to treat (ITT) Ulceration and Erythema.OMAS was only performed in sites were a dentist was available therefore lower numbers in the analysis.

Summary of Oral Mucositis Assessment Scale (OMAS) Ulceration and Erythema Scores Extent of ulceration (grade 0-3) and severity of erythema (grade 0-2) according to the OMAS (Oral Mucositis Assessment Scale) assessed by a dental practitioner twice-weekly over the 28-day study period. The extent of ulceration was rated as follows: 0 no lesion 1. 1 cm2 2. 1-3 cm2 3. \>3 cm2 The severity of erythema was assessed as follows: 0 none 1. not severe 2. severe

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=23 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=25 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Oral Mucositis Assessment Scale (OMAS) Ulceration	0 score Standard Deviation 0.21	0 score Standard Deviation 0.20
Oral Mucositis Assessment Scale (OMAS) Erythema	0.3 score Standard Deviation 0.70	0.5 score Standard Deviation 1.39

SECONDARY outcome

Timeframe: 28 days

Population: Intention to treat (ITT) Hospital stay, days

Duration of hospital stay (time from admission to discharge)

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=57 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=52 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Hospital Stay, Days	23.7 Days Standard Deviation 4.45	24.5 Days Standard Deviation 3.43

SECONDARY outcome

Timeframe: 28 days

Population: Per Protocol (PP)

Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organisation) oral toxicity scale grade 0-4 A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=37 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=49 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Occurence of Oral Mucositis, Per Protocol Population	28 participants	37 participants

SECONDARY outcome

Timeframe: 28 days

Population: Per Protocol (PP). There were 9 patients in the episil +SOC group and 12 patients in the SOC group who had no data for duration of oral mucositis

Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis is graded according to the 5-point oral mucositis WHO scale Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible

Outcome measures

Outcome measures
Measure	Standard-Of-Care + Episil(R) n=28 Participants Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=37 Participants Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Duration of Oral Mucositis, Per Protocol Population	7.4 Days Standard Deviation 5.85	10.1 Days Standard Deviation 5.58

Adverse Events

Standard-Of-Care + Episil(R)

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

Standard-Of-Care

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard-Of-Care + Episil(R) n=57 participants at risk Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=52 participants at risk Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Infections and infestations Septic shock	1.8% 1/57 • Number of events 1 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	1.9% 1/52 • Number of events 1 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
Infections and infestations Pneumonia	1.8% 1/57 • Number of events 1 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	0.00% 0/52 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
General disorders Pyrexia	1.8% 1/57 • Number of events 1 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	0.00% 0/52 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
Respiratory, thoracic and mediastinal disorders Pulmonay haemorrhage	1.8% 1/57 • Number of events 1 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	0.00% 0/52 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application

Other adverse events

Other adverse events
Measure	Standard-Of-Care + Episil(R) n=57 participants at risk Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed episil(R): episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration. Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)	Standard-Of-Care n=52 participants at risk Oral hygiene procedures Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Gastrointestinal disorders Vomiting	17.5% 10/57 • Number of events 10 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	5.8% 3/52 • Number of events 3 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
Gastrointestinal disorders Nausea	12.3% 7/57 • Number of events 7 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	15.4% 8/52 • Number of events 8 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
Gastrointestinal disorders Abdominal pain	8.8% 5/57 • Number of events 5 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	5.8% 3/52 • Number of events 3 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
Blood and lymphatic system disorders Anemia	12.3% 7/57 • Number of events 7 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	9.6% 5/52 • Number of events 5 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
Blood and lymphatic system disorders Thrombocytopenia	12.3% 7/57 • Number of events 7 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	11.5% 6/52 • Number of events 6 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
Blood and lymphatic system disorders febrile neutropenia	8.8% 5/57 • Number of events 5 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	17.3% 9/52 • Number of events 9 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
General disorders Pyrexia	14.0% 8/57 • Number of events 8 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	11.5% 6/52 • Number of events 6 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.0% 4/57 • Number of events 4 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application	7.7% 4/52 • Number of events 4 • Adverse event was collected during the treatment period day 1-28 +follow-up 14 Days +/- 2 Days after last application

Additional Information

Håkan Olsson DDS, PhD

Camurus AB

Phone: +46 46 2863852

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60