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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-021096-85 | EudraCT Number | ||
| U1111-1133-6364 | Registry Identifier | WHO | |
| 2011/776 | Registry Identifier | REK |
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The aim of this clinical trial was to demonstrate the efficacy of a 400 μg dose strength of intranasal fentanyl spray (INFS, Instanyl®) and to evaluate the safety and to establish long term tolerability of treatment with INFS doses of 50, 100, 200 and 400 μg.
This is a clinical trial with 12 weeks treatment of Intranasal fentanyl (INFS) in cancer patients with breakthrough pain (BTP). It was composed of a dose titrated, placebo-controlled, double-blind, randomised, cross-over efficacy phase, combined with a titration and a tolerability phase assessing the safety and nasal tolerability of INFS. The trial is set up with a screening period and three treatment phases: a titration phase (I), an efficacy phase (II) and a tolerability phase (III). The entire trial period for each completed patient consisted of the one week screening period and 12 weeks treatment with INFS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intranasal Fentanyl Spray (INFS) | Experimental | All participants were step-wise titrated to an effective dose of 50, 100, 200 or 400 μg INFS in the Titration Phase (I). Participants titrated to 200 or 400 μg INFS in the Titration Phase were randomized to an 8-spray sequence in the Efficacy Phase (II); 6 BTP episodes were treated with 400 μg INFS and 2 BTP episodes with placebo in a random sequence. Participants entered the Tolerability Phase (III) either directly from the Titration Phase (with an effective dose of 50 or 100 μg) or from the Efficacy Phase (400 μg) and continued with this specific dose, unless adjustment was needed, for a total treatment time of 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intranasal Fentanyl Spray (INFS) | Drug | Applied as 1 puff (= 1 dose) in one nostril, or applied as two puffs (= 2 doses, 1 in each nostril) with ten minutes apart. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment | During the efficacy phase participants assessed their pain intensity at each breakthrough pain (BTP) episode at 0 and 10 minutes after first dose using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID10 is calculated as the difference in pain intensity from time 0 to 10 minutes. A positive value is a decrease (improvement) of the pain; a ≥ 2-point difference is considered as clinically important. | During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Improvement or Worsening in Nasal Mucosa Sign or Abnormality Score | Medical examination of the nasal cavity by rhinoscopy was performed by an oto-rhino-laryngologist before the start of study treatment and at 12 weeks. Signs and any abnormalities were observed for each nostril using the following 4 points assessment scale: • 0 =not present; • 1 =present in a mild degree; • 2 =present in a moderate degree; • 3 =present in a severe degree. A difference in score of 1 or more from Baseline to the end of treatment represented a worsening, while a negative value indicated an improvement of the observed clinical sign. The oto-rhino-laryngologist also assessed whether worsening of a sign was related to study drug. Assessments for both left and right nostrils are presented together. The incidence is calculated as the number of assessments (n) in the improvement or worsening category divided by the number of assessments with a non-missing score for the Nasal Mucosa or Abnormality assessment. Only those signs or abnormalities with n>0 were included |
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Inclusion Criteria:
All inclusion criteria were answered 'yes' for a patient to participate in the clinical trial.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director, Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Budapest | Hungary | |||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25641199 | Derived | Thronaes M, Popper L, Eeg M, Jaatun E, Kvitberg M, Kaasa S. Efficacy and tolerability of intranasal fentanyl spray in cancer patients with breakthrough pain. Clin Ther. 2015 Mar 1;37(3):585-96. doi: 10.1016/j.clinthera.2014.12.010. Epub 2015 Jan 30. |
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The first dose of Intranasal Fentanyl Spray (INFS) was taken at the clinic for training purposes and was not related to treatment of a BTP episode. One patient received the initial 50 μg test dose but did not receive INFS for titration, but is included in the safety analysis set.
Participants took part in the study at 11 investigative sites in Hungary, Norway and Russia from 08 August 2011 to 04 January 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | Intranasal Fentanyl Spray (INFS) | All participants were step-wise titrated to an effective dose of 50, 100, 200 or 400 μg INFS in the Titration Phase (I). Participants titrated to 200 or 400 μg INFS in the Titration Phase were randomized to an 8-spray sequence in the Efficacy Phase (II); 6 BTP episodes were treated with 400 μg INFS and 2 BTP episodes with placebo in a random sequence. Participants entered the Tolerability Phase (III) either directly from the Titration Phase (with an effective dose of 50 or 100 μg) or from the Efficacy Phase (400 μg) and continued with this specific dose, unless adjustment was needed, for a total treatment time of 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Titration Phase |
|
| ||||||||||||||||||||||||
| Efficacy Phase |
| |||||||||||||||||||||||||
| Tolerability Phase |
|
The safety analysis set included all participants who received at least 1 dose of INFS (including the initial test dose).
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| ID | Title | Description |
|---|---|---|
| BG000 | Intranasal Fentanyl Spray (INFS) | All participants were step-wise titrated to an effective dose of 50, 100, 200 or 400 μg INFS in the Titration Phase (I). Participants titrated to 200 or 400 μg INFS in the Titration Phase were randomized to an 8-spray sequence in the Efficacy Phase (II); 6 BTP episodes were treated with 400 μg INFS and 2 BTP episodes with placebo in a random sequence. Participants entered the Tolerability Phase (III) either directly from the Titration Phase (with an effective dose of 50 or 100 μg) or from the Efficacy Phase (400 μg) and continued with this specific dose, unless adjustment was needed, for a total treatment time of 12 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment | During the efficacy phase participants assessed their pain intensity at each breakthrough pain (BTP) episode at 0 and 10 minutes after first dose using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID10 is calculated as the difference in pain intensity from time 0 to 10 minutes. A positive value is a decrease (improvement) of the pain; a ≥ 2-point difference is considered as clinically important. | The Full Analysis Set consisted of all randomly assigned participants who entered the Efficacy Phase (II) of the trial and were treated for at least 1 BTP episode with double-blind INFS in the Efficacy Phase of the trial. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug. |
|
12 weeks
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Titration Phase | Participants were step-wise titrated to an effective dose of 50, 100, 200 or 400 μg INFS in the Titration Phase (I). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiovascular insufficiency | Cardiac disorders | MedDRA version 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-800-778-2860 | clinicaltrialregistry@tpna.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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|
| Placebo | Drug | Matching intranasal placebo spray |
|
| Baseline and at 12 weeks |
| Efficacy Phase: Pain Intensity Difference (PID) at 5, 30, and 60 Minutes After First Dose of Study Drug | During the efficacy phase participants assessed their pain intensity at each breakthrough pain (BTP) episode at 0, 5, 30 and 60 minutes after first dose using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID is calculated as the difference in pain intensity from time 0 to each time point. A positive value is a decrease (improvement) of the pain; a ≥ 2-point difference is considered as clinically important. | During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug. |
| Efficacy Phase: Sum of Pain Intensity Differences (SPID0-60 and SPID0-30) Derived From PI Scores | The SPID30 and SPID60 represent the average improvement in pain intensity over the 30 minute interval and 60 minute interval, respectively. SPIDt was calculated as the area under the curve (AUC) for Pain Intensity Difference over the time interval 0 to t minutes, respectively, divided by the length of the time interval (t minutes). A positive value is a decrease (improvement) of the pain. Pain intensity was assessed at 0, 5, 30 and 60 minutes after study drug using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID is calculated as the difference in pain intensity from time 0 to each time point. | During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug |
| Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 1, 2 or 3 Point Reduction in Pain Intensity | Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment. The following definitions of a positive response were analyzed: • greater than or equal to 1 point reduction in pain intensity (PI) from time 0, • greater than or equal to 2 point reduction in PI from time 0, and • greater than or equal to 3 point reduction in PI from time 0. Pain intensity was assessed using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". | During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug |
| Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 33% or 50% Reduction in Pain Intensity | Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment. The following definitions of a positive response were analyzed: • Greater than 33% reduction in PI from time 0; • Greater than or equal to 50% reduction in PI from time 0. Pain intensity was assessed using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". | During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug |
| Efficacy Phase: General Impression (GI) Score at 60 Minutes After First Dose | Participants assessed their general impression (GI) of treatment efficacy for treated BTP episodes at 60 minutes after first dose of study drug. The validated, categorical 5-point Verbal Rating Scale (VRS) was used for this assessment and scored as follows:
| During the efficacy phase (II), at each episode of breakthrough pain, 60 minutes after first dose of study drug. |
| Number of Participants With Adverse Events (AEs) | The severity (intensity of each AE was assessed as mild (transient symptoms, no interference with daily activities), moderate (marked symptoms, moderate interference with daily activities), or severe (considerable interference with daily activities) by the investigator. Serious adverse events are defined as any untoward medical occurrence that at any dose results in death or is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect. The investigator assessed each AE as either related or not related to study treatment. | 12 weeks |
| Debrecen |
| Hungary |
| Kazincbarcika | Hungary |
| Nyíregyháza | Hungary |
| Pécs | Hungary |
| Drammen | Norway |
| Trondheim | Norway |
| Moscow | Russia |
| Saint Petersburg | Russia |
| Smolensk | Russia |
| Yaroslavl | Russia |
| Unsuccessful titration at any dose |
|
| Less than 3 BTP episodes per week |
|
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Site of Primary Tumour Reported in >5% Patients | Number | participants |
|
| Intranasal Fentanyl Spray (INFS) |
In the Efficacy phase participants received 400 μg INFS for 6 episodes of breakthrough pain. |
| OG001 | Placebo | In the Efficacy Phase Participants received placebo intranasal spray for 2 episodes of breakthrough pain. |
|
|
|
| Secondary | Incidence of Improvement or Worsening in Nasal Mucosa Sign or Abnormality Score | Medical examination of the nasal cavity by rhinoscopy was performed by an oto-rhino-laryngologist before the start of study treatment and at 12 weeks. Signs and any abnormalities were observed for each nostril using the following 4 points assessment scale: • 0 =not present; • 1 =present in a mild degree; • 2 =present in a moderate degree; • 3 =present in a severe degree. A difference in score of 1 or more from Baseline to the end of treatment represented a worsening, while a negative value indicated an improvement of the observed clinical sign. The oto-rhino-laryngologist also assessed whether worsening of a sign was related to study drug. Assessments for both left and right nostrils are presented together. The incidence is calculated as the number of assessments (n) in the improvement or worsening category divided by the number of assessments with a non-missing score for the Nasal Mucosa or Abnormality assessment. Only those signs or abnormalities with n>0 were included | Safety Analysis Set, which included all patients who received at least 1 dose of INFS (including the initial test dose) with non-missing assessments. | Posted | Number | 95% Confidence Interval | proportion of nostril assessments | Baseline and at 12 weeks | Nostrils | Participants |
|
|
|
| Secondary | Efficacy Phase: Pain Intensity Difference (PID) at 5, 30, and 60 Minutes After First Dose of Study Drug | During the efficacy phase participants assessed their pain intensity at each breakthrough pain (BTP) episode at 0, 5, 30 and 60 minutes after first dose using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID is calculated as the difference in pain intensity from time 0 to each time point. A positive value is a decrease (improvement) of the pain; a ≥ 2-point difference is considered as clinically important. | Efficacy Phase, Full Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug. |
|
|
|
| Secondary | Efficacy Phase: Sum of Pain Intensity Differences (SPID0-60 and SPID0-30) Derived From PI Scores | The SPID30 and SPID60 represent the average improvement in pain intensity over the 30 minute interval and 60 minute interval, respectively. SPIDt was calculated as the area under the curve (AUC) for Pain Intensity Difference over the time interval 0 to t minutes, respectively, divided by the length of the time interval (t minutes). A positive value is a decrease (improvement) of the pain. Pain intensity was assessed at 0, 5, 30 and 60 minutes after study drug using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID is calculated as the difference in pain intensity from time 0 to each time point. | Efficacy Phase, Full Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug |
|
|
|
| Secondary | Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 1, 2 or 3 Point Reduction in Pain Intensity | Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment. The following definitions of a positive response were analyzed: • greater than or equal to 1 point reduction in pain intensity (PI) from time 0, • greater than or equal to 2 point reduction in PI from time 0, and • greater than or equal to 3 point reduction in PI from time 0. Pain intensity was assessed using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". | Efficacy Phase, Full Analysis Set | Posted | Number | proportion of breakthrough pain episodes | During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug | breakthrough pain episodes | Participants |
|
|
|
| Secondary | Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 33% or 50% Reduction in Pain Intensity | Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment. The following definitions of a positive response were analyzed: • Greater than 33% reduction in PI from time 0; • Greater than or equal to 50% reduction in PI from time 0. Pain intensity was assessed using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". | Efficacy Phase, Full Analysis Set | Posted | Number | proportion of breakthrough pain episodes | During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug | breakthrough pain episodes | Participants |
|
|
|
| Secondary | Efficacy Phase: General Impression (GI) Score at 60 Minutes After First Dose | Participants assessed their general impression (GI) of treatment efficacy for treated BTP episodes at 60 minutes after first dose of study drug. The validated, categorical 5-point Verbal Rating Scale (VRS) was used for this assessment and scored as follows:
| Efficacy Phase, Full Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | During the efficacy phase (II), at each episode of breakthrough pain, 60 minutes after first dose of study drug. |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) | The severity (intensity of each AE was assessed as mild (transient symptoms, no interference with daily activities), moderate (marked symptoms, moderate interference with daily activities), or severe (considerable interference with daily activities) by the investigator. Serious adverse events are defined as any untoward medical occurrence that at any dose results in death or is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect. The investigator assessed each AE as either related or not related to study treatment. | Safety analysis set | Posted | Number | participants | 12 weeks |
|
|
|
| 2 |
| 45 |
| 22 |
| 45 |
| EG001 | Efficacy Phase | Participants titrated to 200 or 400 μg INFS in the Titration Phase were randomized to an 8-spray sequence in the Efficacy Phase (II); 6 BTP episodes were treated with 400 μg INFS and 2 BTP episodes with placebo in a random sequence. | 2 | 15 | 5 | 15 |
| EG002 | Tolerability Phase | Participants entered the Tolerability Phase (III) either directly from the Titration Phase (with an effective dose of 50 or 100 μg) or from the Efficacy Phase (400 μg) and continued with this specific dose, unless adjustment was needed, for a total treatment time of 12 weeks. | 8 | 31 | 17 | 31 |
| Device occlusion | General disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA version 14.0 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 14.0 | Systematic Assessment |
|
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 14.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Azotaemia | Renal and urinary disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Respiratory depression | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Abdominal hernia | Gastrointestinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Discomfort | General disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 14.0 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA version 14.0 | Systematic Assessment |
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| Irritability | General disorders | MedDRA version 14.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA version 14.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA version 14.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA version 14.0 | Systematic Assessment |
|
| Procedural dizziness | Injury, poisoning and procedural complications | MedDRA version 14.0 | Systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Muscle rigidity | Musculoskeletal and connective tissue disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 14.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Horner's syndrome | Nervous system disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Sedation | Nervous system disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Emotional distress | Psychiatric disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Nasal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Nasal ulcer | Respiratory, thoracic and mediastinal disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA version 14.0 | Systematic Assessment |
|
| Superior vena cava syndrome | Vascular disorders | MedDRA version 14.0 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
|
| Inflammation: Improvement |
|
| Inflammation: Worsening |
|
| Inflammation: Worsening related to study drug |
|
| Sore nose: Improvement |
|
| Sore nose: Worsening |
|
| Sore nose: Worsening related to study drug |
|
| Ulceration: Improvement |
|
| Ulceration: Worsening |
|
| Ulceration: Worsening related to study drug |
|
| Dry nose: Improvement |
|
| Dry nose: Worsening |
|
| Dry nose: Worsening related to study drug |
|
| Runny nose: Improvement |
|
| Runny nose: Worsening |
|
| Runny nose: Worsening related to study drug |
|
| Stuffed nose: Improvement |
|
| Stuffed nose: Worsening |
|
| Stuffed nose: Worsening related to study drug |
|
| Oedema: Improvement |
|
| Oedema: Worsening |
|
| Oedema: Worsening related to study drug |
|
| Epistaxis: Improvement |
|
| Epistaxis: Worsening |
|
| Epistaxis: Worsening related to study drug |
|
| PID at 60 minutes |
|
| ≥ 1 point reduction in PI at 30 minutes |
|
| ≥ 1 point reduction in PI at 60 minutes |
|
| ≥ 2 point reduction in PI at 5 minutes |
|
| ≥ 2 point reduction in PI at 10 minutes |
|
| ≥ 2 point reduction in PI at 30 minutes |
|
| ≥ 2 point reduction in PI at 60 minutes |
|
| ≥ 3 point reduction in PI at 5 minutes |
|
| ≥ 3 point reduction in PI at 10 minutes |
|
| ≥ 3 point reduction in PI at 30 minutes |
|
| ≥ 3 point reduction in PI at 60 minutes |
|
| > 33% reduction in PI at 30 minutes |
|
| > 33% reduction in PI at 60 minutes |
|
| ≥ 50% reduction in PI at 5 minutes |
|
| ≥ 50% reduction in PI at 10 minutes |
|
| ≥ 50% reduction in PI at 30 minutes |
|
| ≥ 50% reduction in PI at 60 minutes |
|
|
| Non-serious adverse events |
|
| Serious adverse events |
|
| Deaths |
|
| Severe adverse events |
|
| AEs leading to withdrawal |
|
| AEs possibly associated with nasal intolerability |
|
| AEs with an onset within 30 minutes of first dose |
|