Clinical Trial Results:
A randomised, two-period cross-over, multicentre, double-blind, single-dose, placebo-controlled trial to assess the local analgesic effect of CAM2028 in head-and-neck cancer patients suffering from radiation-induced oral mucositis
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Summary
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EudraCT number |
2007-000163-26 |
Trial protocol |
BG |
Global end of trial date |
16 Nov 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Apr 2019
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First version publication date |
19 Apr 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
HS-05-161
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Camurus AB
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Sponsor organisation address |
Ideon Science Park, Sölvegatan 41, Lund, Sweden, SE-223 70
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Public contact |
Clinical and Regulatory Development, Camurus AB, +46 462865730, info@camurus.com
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Scientific contact |
Clinical and Regulatory Development, Camurus AB, +46 462865730, info@camurus.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Dec 2007
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Nov 2007
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To prove the local analgesic effect of a new formulation of Benzydamine Hydrochloride (BZD) (CAM2028) over at least six hours after single dosing in subjects with oral mucositis.
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Protection of trial subjects |
The protocol and the statement of informed consent were approved in Bulgaria by an Independent Ethics Committee (IEC) prior to each centre's initiation. The trial was conducted in accordance with the Declaration of Helsinki and its revisions as well as with the valid local and national law(s) of Bulgaria, with the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice (GCP) (E6) issued in July 1996, and with the Commission Directives 2001/20/EC, 2005/28/EC and 2001/83/EC. Written Informed Consent was received from all subjects prior to enrolment into the trial, as dictated by the Declaration of Helsinki.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
19 Jun 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Bulgaria: 38
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Worldwide total number of subjects |
38
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EEA total number of subjects |
38
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
35
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted at five centres in Bulgaria. | |||||||||
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Pre-assignment
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Screening details |
The screening period was up to seven days. Assessments were done as per the schedule of assessment. | |||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
Blinding implementation details |
The investigators, staff at the trial sites, trial monitors, and data analysis/management personnel were blinded to the subject assignment in order to ensure that information that could potentially bias handling of data was not disclosed.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sequence: CAM2028- Placebo | |||||||||
Arm description |
Randomized subjects received CAM2028 on Day 1, and placebo on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
CAM2028
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oromucosal solution
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Routes of administration |
Oromucosal use
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Dosage and administration details |
Dose was 1 mL + 1 mL with 5 min interval between the 2 doses; 30 mg/g BZD (28.2 mg/mL).
One mL of the liquid trial medication was administered into the subject's mouth with a syringe. The subject was to swirl the trial medication around in his or her mouth for approximately 15 seconds to achieve spreading throughout the mouth and then was to spit out any residual formulation. This procedure was repeated after 5 minutes.
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Investigational medicinal product name |
CAM2028 placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oromucosal solution
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Routes of administration |
Oromucosal use
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Dosage and administration details |
Dose was 1 mL + 1 mL with 5 min interval between the 2 doses.
One mL of the liquid trial medication was administered into the subject's mouth with a syringe. The subject was to swirl the trial medication around in his or her mouth for approximately 15 seconds to achieve spreading throughout the mouth and then was to spit out any residual formulation. This procedure was repeated after 5 minutes.
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Arm title
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Sequence: Placebo - CAM2028 | |||||||||
Arm description |
Randomized subjects received placebo on Day 1, and CAM2028 on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
CAM2028 placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oromucosal solution
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Routes of administration |
Oromucosal use
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Dosage and administration details |
Dose was 1 mL + 1 mL with 5 min interval between the 2 doses.
One mL of the liquid trial medication was administered into the subject's mouth with a syringe. The subject was to swirl the trial medication around in his or her mouth for approximately 15 seconds to achieve spreading throughout the mouth and then was to spit out any residual formulation. This procedure was repeated after 5 minutes.
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Investigational medicinal product name |
CAM2028
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oromucosal solution
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Routes of administration |
Oromucosal use
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Dosage and administration details |
Dose was 1 mL + 1 mL with 5 min interval between the 2 doses; 30 mg/g BZD (28.2 mg/mL).
One mL of the liquid trial medication was administered into the subject's mouth with a syringe. The subject was to swirl the trial medication around in his or her mouth for approximately 15 seconds to achieve spreading throughout the mouth and then was to spit out any residual formulation. This procedure was repeated after 5 minutes.
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Baseline characteristics reporting groups
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Reporting group title |
Sequence: CAM2028- Placebo
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Reporting group description |
Randomized subjects received CAM2028 on Day 1, and placebo on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence: Placebo - CAM2028
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Reporting group description |
Randomized subjects received placebo on Day 1, and CAM2028 on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sequence: CAM2028- Placebo
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Reporting group description |
Randomized subjects received CAM2028 on Day 1, and placebo on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. | ||
Reporting group title |
Sequence: Placebo - CAM2028
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Reporting group description |
Randomized subjects received placebo on Day 1, and CAM2028 on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. | ||
Subject analysis set title |
CAM2028 (Full analysis set)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full analysis set included all subjects in the safety set who provided data regarding the primary efficacy variable in both treatment periods.
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Subject analysis set title |
Placebo (Full analysis set)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full analysis set included all subjects in the safety set who provided data regarding the primary efficacy variable in both treatment periods.
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Subject analysis set title |
CAM2028 (Per Protocol Set)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Per-protocol set included all subjects in the full analysis set who completed the trial with no major protocol violations.
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Subject analysis set title |
Placebo (Per Protocol Set)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Per-protocol set included all subjects in the full analysis set who completed the trial with no major protocol violations.
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End point title |
Pain intensity difference (PID) at 6 h after dosing assessed using the 0- 10 Likert pain score [1] | ||||||||||||||||||||
End point description |
The primary variable for this trial was the change in oromucosal pain during six hours after dosing. Data on pain scores were collected using an 11 point Likert pain scale (0=No pain, 10 = Worst possible pain). The subject received a subject diary in which he/she noted the pain score.
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End point type |
Primary
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End point timeframe |
At 6 hours on Days 1 and 3
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: All tests were two-sided with a significance level of 5%. The efficacy parameters were summarised for per protocol set, full analysis set, and each centre for the full analysis set if the centre x treatment interaction was significant. The primary efficacy hypothesis was a confirmatory analysis. Adjustment of alpha-value was not applied. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
PID at 8 hours after dosing | ||||||||||||||||||||
End point description |
PID was measured at 8 hours after dosing using the 0-10 Likert pain score. Data on pain scores were collected using an 11 point Likert pain scale (0=No pain, 10 = Worst possible pain). The subject received a subject diary in which he/she noted the pain score.
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End point type |
Secondary
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End point timeframe |
At 8 hours on Days 1 and 3
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
The area under the curve (AUC) of the pain intensity difference (SPID) during 8 h after dosing | ||||||||||||||||||||
End point description |
AUC of pain intensity difference during 8 h after dosing was assessed. Data on pain scores were collected using an 11 point Likert pain scale (0=No pain, 10 = Worst possible pain). The subject received a subject diary in which he/she noted the pain score.
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End point type |
Secondary
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End point timeframe |
At 8 hours on Days 1 and 3
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Peak pain intensity difference (PPID) during 8 h after dosing, the maximal pain intensity | ||||||||||||||||||||
End point description |
PPID during 8 h after dosing was assessed. Data on pain scores were collected using an 11 point Likert pain scale (0=No pain, 10 = Worst possible pain). The subject received a subject diary in which he/she noted the pain score.
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End point type |
Secondary
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End point timeframe |
At 8 hours on Days 1 and 3
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Difficulty in swallowing intensity before and after lunch and dinner on the day of dosing | ||||||||||||||||||||||||
End point description |
To assess the functional response to a single dose of trial medication in terms of difficulty in swallowing. Data on difficulty in swallowing was collected 30 minutes before and 30 minutes after each meal using a 11 point Likert scale (0=No difficulty, 10 = Worst possible difficulty). The score was noted in the subject diary.
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End point type |
Secondary
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End point timeframe |
At 30 min before and after meals on Day 1 and Day 3
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Difficulty in swallowing intensity before and after lunch and dinner on the day of dosing | ||||||||||||||||||||||||
End point description |
To assess the functional response to a single dose of trial medication in terms of difficulty in swallowing. Data on difficulty in swallowing was collected 30 minutes before and 30 minutes after each meal using a 11 point Likert scale (O=No difficulty, 10 = Worst possible difficulty). The score was noted in the subject diary.
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End point type |
Secondary
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End point timeframe |
At 30 min before and after meals on Day 1 and Day 3
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Minimum difficulty in swallowing during 24 h after dosing | ||||||||||||||||||||
End point description |
To assess the functional response to a single dose of trial medication in terms of difficulty in swallowing. Data on difficulty in swallowing was collected 30 minutes before and 30 minutes after each meal using a 11 point Likert scale (0=No difficulty, 10 = Worst possible difficulty). The score was noted in the subject diary.
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End point type |
Secondary
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End point timeframe |
At 24 hours on Days 1 to 5
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| No statistical analyses for this end point | |||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Days 1, 3, and 5
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Adverse event reporting additional description |
An adverse event (AE) was any untoward medical occurrence in a subject administered a pharmaceutical product which did not necessarily have a causal relationship with the treatment.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.0
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Reporting groups
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Reporting group title |
CAM2028
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Reporting group description |
For the Sequence: CAM2028- Placebo, randomized subjects received CAM2028 on Day 1, and placebo on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. For the Sequence: Placebo - CAM2028, randomized subjects received placebo on Day 1, and CAM2028 on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
For the Sequence: CAM2028- Placebo, randomized subjects received CAM2028 on Day 1, and placebo on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. For the Sequence: Placebo - CAM2028, randomized subjects received placebo on Day 1, and CAM2028 on Day 3. Subjects were treated with trial medication after radiotherapy on Days 1 and 3, respectively. There was a >24 hour wash-out period between treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
