Oral Mucositis
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Clonidine Lauriad® to treat chemoradiation therapy induced severe oral mucositis in patients with head and neck cancer.
Interventions
DRUGClonidine Lauriad® 50µg
50µg muco-adhesive buccal tablet once day every day up to 8 weeks
DRUGClonidine Lauriad® 100µg
100µg muco-adhesive buccal tablets, once a day, every day up to 8 weeks
DRUGPlacebo Lauriad®
placebo muco-adhesive buccal tablets, once a day, every day up to 8 weeks
Sponsors
Valerio Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female * Aged \> 18 years * Suffering from a newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx histologically-confirmed and having undergone resective surgery * Prior neoadjuvant chemotherapy allowed provided that, the patient did not experience a World Health Organization (WHO) grade \> 2 oral mucositis during the neoadjuvant therapy. * Patient eligible to receive concurrent chemo-radiation defined as: 1. A continuous course of conventional external beam irradiation (IMRT eligible) with a minimum cumulative radiation dose of 50 Gy or a maximum of 70 Gy, based on a daily dosing between 1.8 and 2.2 Gy combined with platinum based chemotherapy on a weekly or tri-weekly cycles. 2. Planned radiation treatment fields must include at least two oral tissue sites (among right or left buccal mucosa, floor of mouth, tongue, right or left soft palate) with each site receiving a total of 50 Gy or a maximum of 70 Gy. The radiation treatment plan will be reviewed by a designated radiation oncologist. * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 * Screening laboratory tests: 1. Haemoglobin ≥ 10g/dL 2. Absolute neutrophil counts ≥ 1500 cells/mm3 3. Platelets ≥ 100.000/mm3 4. Conjugated bilirubin ≤ 2 times Upper Limit of Normal (ULN) 5. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 ULN 6. Negative serum pregnancy test * Women of child bearing potential must have effective contraception method (oral or device) * Signed written informed consent
Exclusion criteria
* Tumours of the lips, sinuses, salivary glands * Prior radiation of the head and neck area * Curative surgery less than 2 weeks or more than 15 weeks prior to the initiation of radiation therapy-chemotherapy (RT-CT) * Presence of active infectious disease * Presence of active oral infectious disease, including oropharyngeal candidiasis and/or orofacial herpes * Presence of oral mucositis * Known or suspected chronic viral diseases including HIV * Systolic blood pressure \< 100 mmHg and/or Diastolic blood pressure \< 50 mmHg * Recent stroke within the last 6 months * Bradyarrhythmia (\<60 b/min), including sinus node dysfunction or atrioventricular (AV) nodal conduction block 2nd or 3rd degree * Subjects with orthostatic hypotension, defined by a decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up * Renal insufficiency (creatinine blood level \> 1.5ULN) * Ongoing heavy alcohol consumption (\>100g alcohol/day) * Administration of any concomitant treatment likely to interfere with clonidine * Known hypersensitivity to clonidine, history of allergy or intolerance to milk proteins or any other component of the product * Presence of severe or uncontrolled depression * Pregnant or breast-feeding women * Inability to give informed consent or comply with study requirements * Unable or unwilling to comply with follow-up visits * Participation to a clinical trial within 30 days prior to randomization and during the entire duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed | 8 weeks | The primary endpoint planned in the protocol was the percentage of participants with an oral mucositis score greater than or equal to 3 using the WHO oral mucositis severity scale at a cumulative radiation dose of 50 Gy. This was modified by protocol amendment to the cumulative radiation dose at which a WHO score greater than or equal to 3 was first observed. This change was made to account for the fact that in real practice most patients receive a cumulative dose between 60 and 70 Gy. The presence of grade 3 or 4 oral mucositis was assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = oral ulcers, liquid diet only; WHO score 4 = oral alimentation impossible. Each assessment was associated with the actual cumulative dose of radiotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| At Least One Opioid Use (Class 3 Analgesic) | 8 weeks | Opioid use was recorded twice weekly during the active phase (radiotherapy) |
| Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation) | 8 weeks | Opioid use was recorded twice weekly for up to 8 weeks during the active phase (radiotherapy). The sum of non-missing total cumulative doses across all class 3 analgesics recorded for the considered participant is reported. |
| Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range) | 8 weeks | Opioid use was recorded twice weekly for up to 8 weeks during the active phase (radiotherapy). The sum of non-missing total cumulative doses across all class 3 analgesics recorded for the considered participant is reported. |
| Overall Survival | 2 years | After the end-of study visit, the investigator center collects OS follow-up data for each patient who has consented to participate in the follow-up data collection. the OS follow-up period was still ongoing at time of the primary analysis and ended in Nov 2016. The analysis was condicted on the ITT population. The overall survival was evaluate every 6 months after last subject completed in patients who has consented to participate . |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Severe Oral Mucositis | 8 weeks | Time to onset is the duration until first Severe Oral Mucositis. Severe Oral Mucositis was defined as a Grade 3 or Grade 4 score on the World Health Organization (WHO) oral mucositis severity scale. Participants were assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = ulcers, extensive erythema, and the inability of the participant to swallow a solid diet; WHO score 4 = mucositis to the extent that alimentation was not possible. |
| The Maximum Severity of Oral Mucositis | 8 weeks | Participants were assessed using the World Health Organization (WHO) oral mucositis severity scale twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. The WHO scores were as follows: 0 = None; 1 = oral soreness, erythema; 2 = oral erythema, ulcers, solid diet tolerated; 3 = oral ulcers, liquid diet only; 4 = oral alimentation impossible. The maximum severity was the maximum score reported during the active phase. |
| The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | 8 weeks | The presence of grade 3 or 4 oral mucositis on the World Health Organization (WHO) oral mucositis severity scale was assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = ulcers, extensive erythema, and the inability of the participant to swallow a solid diet; WHO score 4 = mucositis to the extent that alimentation was not possible.The number of participants with at least one Grade 3 or Grade 4 mucositis score during the active phase is reported. |
| Salivary Flow Assessment Using the National Cancer Institute-Common Terminology Criteria (NCI-CTC) for Xerostomia: Time to First Grade 2 or Higher | 8 weeks | Salivary flow was assessed and scored by the investigator weekly using the NCI-CTC scale for xerostomia for up to 8 weeks during the active phase (radiotherapy). Time to appearance of Grade 2 or higher on the following 4-point scoring scale is reported: 0 = normal; 1 = symptomatic (dry or thick saliva) without significant dietary alteration (unstimulated saliva flow greater than 0.2 mL/minute); 2 = symptomatic and significant oral intake alterations (e.g. copious water, other lubricants, diet limited to purees and/or soft, moist foods) (unstimulated saliva 0.1 to 0.2 mL/minute); and 3 = symptoms leading to inability to adequately aliment orally, intravenous fluids, tube feedings, or total parenteral nutrition indicated (unstimulated saliva \< 0.1 mL/minute). |
| Overall Treatment Compliance According to the Patient Diary | 8 weeks | All participants complete a daily questionnaire during the active phase (radiotherapy). Compliance = \[ number of tablets / (end date of treatment - start date treatment + 1 ) \] \* 100. The number of tablets is the number of days with a tablet applied and treatment start and end dates are the first and last dates of the patient diary with a tablet applied. |
Countries
France, Germany, Hungary, Spain, Switzerland, United States
Participant flow
Recruitment details
183 participants were randomized from 6 countries during 4 years
Participants by arm
| Arm | Count |
|---|---|
| Clonidine Lauriad® 50 µg Clonidine Lauriad® 50 µg: 50µg muco-adhesive buccal tablet once a day every day up to 8 weeks | 56 |
| Clonidine Lauriad® 100 µg Clonidine Lauriad® 100 µg: 100µg muco-adhesive buccal tablets once a day every day up to 8 weeks | 65 |
| Placebo Lauriad® Placebo Lauriad®: placebo muco-adhesive buccal tablets, once a day every day up to 8 weeks | 62 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 | 1 |
| Overall Study | Noncompliance | 3 | 1 | 6 |
| Overall Study | Other | 1 | 7 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 5 |
Baseline characteristics
| Characteristic | Total | Placebo Lauriad® | Clonidine Lauriad® 50 µg | Clonidine Lauriad® 100 µg |
|---|---|---|---|---|
| Age, Continuous | 57.3 years | 56.6 years | 58.8 years | 55.7 years |
| Age, Customized 18 to 64 years | 151 participants | 50 participants | 43 participants | 58 participants |
| Age, Customized 65 to 84 years | 32 participants | 12 participants | 13 participants | 7 participants |
| Age, Customized 85 years and over | 0 participants | 0 participants | 0 participants | 0 participants |
| Body Mass Index (BMI) | 23.59 kg/m^2 | 23.33 kg/m^2 | 23.7 kg/m^2 | 23.66 kg/m^2 |
| Disease duration | 2 months | 2 months | 2 months | 2 months |
| Disease location Hypopharynx | 8 participants | 2 participants | 4 participants | 2 participants |
| Disease location Larynx | 15 participants | 5 participants | 4 participants | 6 participants |
| Disease location Oral cavity | 93 participants | 30 participants | 26 participants | 37 participants |
| Disease location Oral cavity/hypopharynx | 2 participants | 1 participants | 0 participants | 1 participants |
| Disease location Oral cavity/larynx | 1 participants | 0 participants | 1 participants | 0 participants |
| Disease location Oral cavity/oropharynx | 2 participants | 1 participants | 0 participants | 1 participants |
| Disease location Oropharynx | 57 participants | 21 participants | 19 participants | 17 participants |
| Disease location Oropharynx/hypopharynx | 4 participants | 1 participants | 2 participants | 1 participants |
| Disease location Oropharynx/larynx | 1 participants | 1 participants | 0 participants | 0 participants |
| Disease location in oral cavity or oropharynx No | 23 participants | 7 participants | 8 participants | 8 participants |
| Disease location in oral cavity or oropharynx Yes | 160 participants | 55 participants | 48 participants | 57 participants |
| Eastern Cooperative Oncology Group (ECOG) Score Score 0 | 125 participants | 42 participants | 42 participants | 41 participants |
| Eastern Cooperative Oncology Group (ECOG) Score Score 1 | 56 participants | 20 participants | 14 participants | 22 participants |
| Eastern Cooperative Oncology Group (ECOG) Score Score 2 | 2 participants | 0 participants | 0 participants | 2 participants |
| Height | 171 cm | 172 cm | 171 cm | 170 cm |
| Mucosal irritation Missing | 1 participants | 0 participants | 1 participants | 0 participants |
| Mucosal irritation No | 177 participants | 61 participants | 53 participants | 63 participants |
| Mucosal irritation Yes | 5 participants | 1 participants | 2 participants | 2 participants |
| Oral infection Missing | 1 participants | 0 participants | 1 participants | 0 participants |
| Oral infection No | 181 participants | 62 participants | 55 participants | 64 participants |
| Oral infection Yes | 1 participants | 0 participants | 0 participants | 1 participants |
| Prior radiotherapy and/or chemotherapy No | 6 participants | 1 participants | 2 participants | 3 participants |
| Prior radiotherapy and/or chemotherapy Yes | 177 participants | 61 participants | 54 participants | 62 participants |
| Prior surgery No | 3 participants | 1 participants | 1 participants | 1 participants |
| Prior surgery Yes | 180 participants | 61 participants | 55 participants | 64 participants |
| Race/Ethnicity, Customized Black | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Caucasian | 173 participants | 59 participants | 53 participants | 61 participants |
| Race/Ethnicity, Customized Other | 9 participants | 3 participants | 2 participants | 4 participants |
| Region of Enrollment France | 88 participants | 30 participants | 31 participants | 27 participants |
| Region of Enrollment Germany | 31 participants | 10 participants | 10 participants | 11 participants |
| Region of Enrollment Hungary | 4 participants | 0 participants | 1 participants | 3 participants |
| Region of Enrollment Spain | 52 participants | 18 participants | 14 participants | 20 participants |
| Region of Enrollment Switzerland | 2 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 6 participants | 4 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 45 Participants | 13 Participants | 16 Participants | 16 Participants |
| Sex: Female, Male Male | 138 Participants | 49 Participants | 40 Participants | 49 Participants |
| Tooth extraction Missing | 2 participants | 0 participants | 1 participants | 1 participants |
| Tooth extraction No | 87 participants | 30 participants | 25 participants | 32 participants |
| Tooth extraction Yes | 94 participants | 32 participants | 30 participants | 32 participants |
| Weight | 69 kg | 69 kg | 71.3 kg | 66 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 48 / 55 | 60 / 64 | 61 / 62 | 108 / 119 |
| serious Total, serious adverse events | 16 / 55 | 21 / 64 | 14 / 62 | 37 / 119 |
Outcome results
Primary
Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed
The primary endpoint planned in the protocol was the percentage of participants with an oral mucositis score greater than or equal to 3 using the WHO oral mucositis severity scale at a cumulative radiation dose of 50 Gy. This was modified by protocol amendment to the cumulative radiation dose at which a WHO score greater than or equal to 3 was first observed. This change was made to account for the fact that in real practice most patients receive a cumulative dose between 60 and 70 Gy. The presence of grade 3 or 4 oral mucositis was assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = oral ulcers, liquid diet only; WHO score 4 = oral alimentation impossible. Each assessment was associated with the actual cumulative dose of radiotherapy.
Time frame: 8 weeks
Population: The analysis was conducted on the Intent to treat population, defined as all participants who received at least one dose of investigational drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clonidine Lauriad® 50 µg | Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed | 66 Cumulative radiation dose (Gy) |
| Clonidine Lauriad® 100 µg | Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed | 56 Cumulative radiation dose (Gy) |
| Placebo Lauriad® | Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed | 48 Cumulative radiation dose (Gy) |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | Cumulative Radiation Dose at Which Severe Oral Mucositis (World Health Organization [WHO] Score ≥ 3) Was First Observed | 60 Cumulative radiation dose (Gy) |
p-value: 0.16595% CI: [0.387, 1.186]Log Rank
p-value: 0.42195% CI: [0.495, 1.35]Log Rank
p-value: 0.21195% CI: [0.484, 1.175]Log Rank
Secondary
At Least One Opioid Use (Class 3 Analgesic)
Opioid use was recorded twice weekly during the active phase (radiotherapy)
Time frame: 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clonidine Lauriad® 50 µg | At Least One Opioid Use (Class 3 Analgesic) | Yes | 23 participants |
| Clonidine Lauriad® 50 µg | At Least One Opioid Use (Class 3 Analgesic) | Missing | 2 participants |
| Clonidine Lauriad® 50 µg | At Least One Opioid Use (Class 3 Analgesic) | No | 31 participants |
| Clonidine Lauriad® 100 µg | At Least One Opioid Use (Class 3 Analgesic) | Yes | 30 participants |
| Clonidine Lauriad® 100 µg | At Least One Opioid Use (Class 3 Analgesic) | No | 34 participants |
| Clonidine Lauriad® 100 µg | At Least One Opioid Use (Class 3 Analgesic) | Missing | 1 participants |
| Placebo Lauriad® | At Least One Opioid Use (Class 3 Analgesic) | Missing | 0 participants |
| Placebo Lauriad® | At Least One Opioid Use (Class 3 Analgesic) | No | 32 participants |
| Placebo Lauriad® | At Least One Opioid Use (Class 3 Analgesic) | Yes | 30 participants |
Secondary
Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation)
Opioid use was recorded twice weekly for up to 8 weeks during the active phase (radiotherapy). The sum of non-missing total cumulative doses across all class 3 analgesics recorded for the considered participant is reported.
Time frame: 8 weeks
Population: Participants with at least one use of an opioid during the active phase with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clonidine Lauriad® 50 µg | Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation) | 469.31 morphine dose equivalent | Standard Deviation 633.51 |
| Clonidine Lauriad® 100 µg | Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation) | 415.49 morphine dose equivalent | Standard Deviation 490.55 |
| Placebo Lauriad® | Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation) | 624.94 morphine dose equivalent | Standard Deviation 958.81 |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | Opioid Use: Minimal Total Cumulative Dose Administered (Mean, Standard Deviation) | 439.95 morphine dose equivalent | Standard Deviation 553.88 |
Secondary
Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range)
Opioid use was recorded twice weekly for up to 8 weeks during the active phase (radiotherapy). The sum of non-missing total cumulative doses across all class 3 analgesics recorded for the considered participant is reported.
Time frame: 8 weeks
Population: Participants with at least one use of an opioid during the active phase with evaluable data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clonidine Lauriad® 50 µg | Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range) | 183.6 morphine dose equivalent |
| Clonidine Lauriad® 100 µg | Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range) | 174 morphine dose equivalent |
| Placebo Lauriad® | Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range) | 215 morphine dose equivalent |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | Opioid Use: Minimal Total Cumulative Dose Administered (Median, Range) | 178.65 morphine dose equivalent |
p-value: 0.807Wilcoxon (Mann-Whitney)
p-value: 0.971Wilcoxon (Mann-Whitney)
Secondary
Overall Survival
After the end-of study visit, the investigator center collects OS follow-up data for each patient who has consented to participate in the follow-up data collection. the OS follow-up period was still ongoing at time of the primary analysis and ended in Nov 2016. The analysis was condicted on the ITT population. The overall survival was evaluate every 6 months after last subject completed in patients who has consented to participate .
Time frame: 2 years
Population: The population for the 2-year OS follow-up was the ITT defined as all patients who received at least 1 dose of investigational drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clonidine Lauriad® 50 µg | Overall Survival | 47 months |
| Clonidine Lauriad® 100 µg | Overall Survival | 58.8 months |
| Placebo Lauriad® | Overall Survival | 41.8 months |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | Overall Survival | 58.8 months |
Other Pre-specified
Overall Treatment Compliance According to the Patient Diary
All participants complete a daily questionnaire during the active phase (radiotherapy). Compliance = \[ number of tablets / (end date of treatment - start date treatment + 1 ) \] \* 100. The number of tablets is the number of days with a tablet applied and treatment start and end dates are the first and last dates of the patient diary with a tablet applied.
Time frame: 8 weeks
Population: Participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clonidine Lauriad® 50 µg | Overall Treatment Compliance According to the Patient Diary | 94.28 percentage of compliance | Standard Deviation 8.23 |
| Clonidine Lauriad® 100 µg | Overall Treatment Compliance According to the Patient Diary | 93.12 percentage of compliance | Standard Deviation 11.89 |
| Placebo Lauriad® | Overall Treatment Compliance According to the Patient Diary | 96.12 percentage of compliance | Standard Deviation 5.59 |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | Overall Treatment Compliance According to the Patient Diary | 93.66 percentage of compliance | Standard Deviation 10.34 |
Other Pre-specified
Salivary Flow Assessment Using the National Cancer Institute-Common Terminology Criteria (NCI-CTC) for Xerostomia: Time to First Grade 2 or Higher
Salivary flow was assessed and scored by the investigator weekly using the NCI-CTC scale for xerostomia for up to 8 weeks during the active phase (radiotherapy). Time to appearance of Grade 2 or higher on the following 4-point scoring scale is reported: 0 = normal; 1 = symptomatic (dry or thick saliva) without significant dietary alteration (unstimulated saliva flow greater than 0.2 mL/minute); 2 = symptomatic and significant oral intake alterations (e.g. copious water, other lubricants, diet limited to purees and/or soft, moist foods) (unstimulated saliva 0.1 to 0.2 mL/minute); and 3 = symptoms leading to inability to adequately aliment orally, intravenous fluids, tube feedings, or total parenteral nutrition indicated (unstimulated saliva \< 0.1 mL/minute).
Time frame: 8 weeks
Population: Two of the 183 participants received study treatment but withdrew early without any safety assessments (1 in the clonidine Lauriad 50 μg group and 1 in the clonidine Lauriad 100 μg group). The safety population therefore included 181 participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clonidine Lauriad® 50 µg | Salivary Flow Assessment Using the National Cancer Institute-Common Terminology Criteria (NCI-CTC) for Xerostomia: Time to First Grade 2 or Higher | 6 weeks |
| Clonidine Lauriad® 100 µg | Salivary Flow Assessment Using the National Cancer Institute-Common Terminology Criteria (NCI-CTC) for Xerostomia: Time to First Grade 2 or Higher | 7.4 weeks |
| Placebo Lauriad® | Salivary Flow Assessment Using the National Cancer Institute-Common Terminology Criteria (NCI-CTC) for Xerostomia: Time to First Grade 2 or Higher | 5.1 weeks |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | Salivary Flow Assessment Using the National Cancer Institute-Common Terminology Criteria (NCI-CTC) for Xerostomia: Time to First Grade 2 or Higher | 7.1 weeks |
p-value: 0.38895% CI: [0.484, 1.401]Log Rank
p-value: 0.05495% CI: [0.357, 1.012]Log Rank
p-value: 0.10295% CI: [0.444, 1.078]Log Rank
Other Pre-specified
The Maximum Severity of Oral Mucositis
Participants were assessed using the World Health Organization (WHO) oral mucositis severity scale twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. The WHO scores were as follows: 0 = None; 1 = oral soreness, erythema; 2 = oral erythema, ulcers, solid diet tolerated; 3 = oral ulcers, liquid diet only; 4 = oral alimentation impossible. The maximum severity was the maximum score reported during the active phase.
Time frame: 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clonidine Lauriad® 50 µg | The Maximum Severity of Oral Mucositis | Grade 0 | 7 participants |
| Clonidine Lauriad® 50 µg | The Maximum Severity of Oral Mucositis | Grade 1 | 9 participants |
| Clonidine Lauriad® 50 µg | The Maximum Severity of Oral Mucositis | Grade 2 | 15 participants |
| Clonidine Lauriad® 50 µg | The Maximum Severity of Oral Mucositis | Grade 3 | 17 participants |
| Clonidine Lauriad® 50 µg | The Maximum Severity of Oral Mucositis | Grade 4 | 6 participants |
| Clonidine Lauriad® 50 µg | The Maximum Severity of Oral Mucositis | No value during the concerned period | 2 participants |
| Clonidine Lauriad® 100 µg | The Maximum Severity of Oral Mucositis | No value during the concerned period | 2 participants |
| Clonidine Lauriad® 100 µg | The Maximum Severity of Oral Mucositis | Grade 3 | 20 participants |
| Clonidine Lauriad® 100 µg | The Maximum Severity of Oral Mucositis | Grade 0 | 6 participants |
| Clonidine Lauriad® 100 µg | The Maximum Severity of Oral Mucositis | Grade 2 | 20 participants |
| Clonidine Lauriad® 100 µg | The Maximum Severity of Oral Mucositis | Grade 1 | 7 participants |
| Clonidine Lauriad® 100 µg | The Maximum Severity of Oral Mucositis | Grade 4 | 10 participants |
| Placebo Lauriad® | The Maximum Severity of Oral Mucositis | Grade 1 | 9 participants |
| Placebo Lauriad® | The Maximum Severity of Oral Mucositis | Grade 2 | 11 participants |
| Placebo Lauriad® | The Maximum Severity of Oral Mucositis | Grade 3 | 30 participants |
| Placebo Lauriad® | The Maximum Severity of Oral Mucositis | No value during the concerned period | 2 participants |
| Placebo Lauriad® | The Maximum Severity of Oral Mucositis | Grade 4 | 6 participants |
| Placebo Lauriad® | The Maximum Severity of Oral Mucositis | Grade 0 | 4 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Maximum Severity of Oral Mucositis | Grade 4 | 16 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Maximum Severity of Oral Mucositis | No value during the concerned period | 4 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Maximum Severity of Oral Mucositis | Grade 1 | 16 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Maximum Severity of Oral Mucositis | Grade 3 | 37 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Maximum Severity of Oral Mucositis | Grade 0 | 13 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Maximum Severity of Oral Mucositis | Grade 2 | 35 participants |
p-value: 0.176Kruskal-Wallis
p-value: 0.61Kruskal-Wallis
p-value: 0.295Kruskal-Wallis
Other Pre-specified
The Overall Incidence of Grade 3/4 Mucositis During the Active Phase.
The presence of grade 3 or 4 oral mucositis on the World Health Organization (WHO) oral mucositis severity scale was assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = ulcers, extensive erythema, and the inability of the participant to swallow a solid diet; WHO score 4 = mucositis to the extent that alimentation was not possible.The number of participants with at least one Grade 3 or Grade 4 mucositis score during the active phase is reported.
Time frame: 8 weeks
Population: Missing = participants without a WHO score during the active phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clonidine Lauriad® 50 µg | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | Missing | 2 participants |
| Clonidine Lauriad® 50 µg | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | Yes | 23 participants |
| Clonidine Lauriad® 50 µg | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | No | 31 participants |
| Clonidine Lauriad® 100 µg | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | Missing | 2 participants |
| Clonidine Lauriad® 100 µg | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | Yes | 30 participants |
| Clonidine Lauriad® 100 µg | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | No | 33 participants |
| Placebo Lauriad® | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | No | 24 participants |
| Placebo Lauriad® | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | Missing | 2 participants |
| Placebo Lauriad® | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | Yes | 36 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | Missing | 4 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | Yes | 53 participants |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | The Overall Incidence of Grade 3/4 Mucositis During the Active Phase. | No | 64 participants |
p-value: 0.063Chi-squared
p-value: 0.169Chi-squared
p-value: 0.064Chi-squared
Other Pre-specified
Time to Onset of Severe Oral Mucositis
Time to onset is the duration until first Severe Oral Mucositis. Severe Oral Mucositis was defined as a Grade 3 or Grade 4 score on the World Health Organization (WHO) oral mucositis severity scale. Participants were assessed twice weekly during the active phase (radiotherapy) by a trained radiation oncologist or an ear nose and throat specialist who took into account the field of radiation treatment. WHO score 3 = ulcers, extensive erythema, and the inability of the participant to swallow a solid diet; WHO score 4 = mucositis to the extent that alimentation was not possible.
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clonidine Lauriad® 50 µg | Time to Onset of Severe Oral Mucositis | 6.4 weeks |
| Clonidine Lauriad® 100 µg | Time to Onset of Severe Oral Mucositis | 6 weeks |
| Placebo Lauriad® | Time to Onset of Severe Oral Mucositis | 5.1 weeks |
| Clonidine Lauriad® Muco-adhesive Buccal Tablets Pooled | Time to Onset of Severe Oral Mucositis | 6.4 weeks |
p-value: 0.19995% CI: [0.398, 1.223]Log Rank
p-value: 0.42495% CI: [0.493, 1.353]Log Rank
p-value: 0.23595% CI: [0.489, 1.193]Log Rank