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A Clinical Trial With Intranasal Fentanyl in Cancer Patients With Breakthrough Pain (NOSE-400)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01429051
Recruitment Status : Completed
First Posted : September 5, 2011
Results First Posted : March 26, 2014
Last Update Posted : March 26, 2014
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Break Through Pain
Cancer
Interventions Drug: Intranasal Fentanyl Spray (INFS)
Drug: Placebo
Enrollment 46
Recruitment Details Participants took part in the study at 11 investigative sites in Hungary, Norway and Russia from 08 August 2011 to 04 January 2013.
Pre-assignment Details 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.
Arm/Group Title Intranasal Fentanyl Spray (INFS)
Hide Arm/Group Description 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.
Period Title: Titration Phase
Started 45
Completed 33
Not Completed 12
Reason Not Completed
Death             1
Withdrawal by Subject             7
Physician Decision             1
Unsuccessful titration at any dose             1
Less than 3 BTP episodes per week             2
Period Title: Efficacy Phase
Started 15 [1]
Completed 13
Not Completed 2
Reason Not Completed
Adverse Event             1
Death             1
[1]
Participants titrated to 200 or 400 μg INFS in Titration Phase
Period Title: Tolerability Phase
Started 31 [1]
Completed 16
Not Completed 15
Reason Not Completed
Death             5
Adverse Event             2
Withdrawal by Subject             5
Physician Decision             1
Other             2
[1]
Participants entered directly from the Titration or Efficacy Phase
Arm/Group Title Intranasal Fentanyl Spray (INFS)
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 46
Hide Baseline Analysis Population Description
The safety analysis set included all participants who received at least 1 dose of INFS (including the initial test dose).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 46 participants
61.0  (9.09)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 46 participants
Female
31
  67.4%
Male
15
  32.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White Number Analyzed 46 participants
46
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 46 participants
Hungary 33
Norway 10
Russian Federation 3
Site of Primary Tumour Reported in >5% Patients  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 46 participants
Breast 14
Lung respiratory system 5
Gastro-oesophageal 1
Colon/rectal 3
Pancreas 6
Female genital 3
Prostate 3
Urological 7
Unknown Primary Tumour 2
Liver 1
Other 1
1.Primary Outcome
Title Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment
Hide Description 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.
Time Frame During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Intranasal Fentanyl Spray (INFS) Placebo
Hide Arm/Group Description:
In the Efficacy phase participants received 400 μg INFS for 6 episodes of breakthrough pain.
In the Efficacy Phase Participants received placebo intranasal spray for 2 episodes of breakthrough pain.
Overall Number of Participants Analyzed 15 15
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
2.5
(1.42 to 3.49)
1.4
(0.23 to 2.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intranasal Fentanyl Spray (INFS), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed Models Analysis
Comments A mixed effects model with episode baseline PI as a covariate, treatment as a fixed effect and patient as a random effect.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.41 to 1.179
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Incidence of Improvement or Worsening in Nasal Mucosa Sign or Abnormality Score
Hide Description 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
Time Frame Baseline and at 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set, which included all patients who received at least 1 dose of INFS (including the initial test dose) with non-missing assessments.
Arm/Group Title Intranasal Fentanyl Spray (INFS)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 46
Overall Number of Units Analyzed
Type of Units Analyzed: Nostrils
54
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of nostril assessments
Change of color: Improvement
0.06
(0.00 to 0.12)
Change of color: Worsening
0.09
(0.02 to 0.17)
Change of color: Worsening related to study drug
0.09
(0.02 to 0.17)
Inflammation: Improvement
0.04
(0.00 to 0.09)
Inflammation: Worsening
0.07
(0.00 to 0.14)
Inflammation: Worsening related to study drug
0.07
(0.00 to 0.14)
Sore nose: Improvement
0.04
(0.00 to 0.09)
Sore nose: Worsening
0.04
(0.00 to 0.09)
Sore nose: Worsening related to study drug
0.04
(0.00 to 0.09)
Ulceration: Improvement
NA [1] 
(NA to NA)
Ulceration: Worsening
0.04
(0.00 to 0.09)
Ulceration: Worsening related to study drug
0.04
(0.00 to 0.09)
Dry nose: Improvement
0.09
(0.02 to 0.17)
Dry nose: Worsening
0.06
(0.00 to 0.12)
Dry nose: Worsening related to study drug
NA [2] 
(NA to NA)
Runny nose: Improvement
0.04
(0.00 to 0.09)
Runny nose: Worsening
0.13
(0.04 to 0.22)
Runny nose: Worsening related to study drug
0.10
(0.02 to 0.18)
Stuffed nose: Improvement
0.06
(0.00 to 0.12)
Stuffed nose: Worsening
0.17
(0.07 to 0.27)
Stuffed nose: Worsening related to study drug
0.08
(0.00 to 0.15)
Oedema: Improvement
0.04
(0.00 to 0.09)
Oedema: Worsening
0.17
(0.07 to 0.27)
Oedema: Worsening related to study drug
0.08
(0.00 to 0.15)
Epistaxis: Improvement
0.02
(0.00 to 0.05)
Epistaxis: Worsening
0.02
(0.00 to 0.05)
Epistaxis: Worsening related to study drug
0.02
(0.00 to 0.05)
[1]
No participants achieved ulceration improvement.
[2]
No participants achieved worsening of dry nose related to study drug.
3.Secondary Outcome
Title Efficacy Phase: Pain Intensity Difference (PID) at 5, 30, and 60 Minutes After First Dose of Study Drug
Hide Description 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.
Time Frame During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Phase, Full Analysis Set
Arm/Group Title Intranasal Fentanyl Spray (INFS) Placebo
Hide Arm/Group Description:
In the Efficacy phase participants received 400 μg INFS for 6 episodes of breakthrough pain.
In the Efficacy Phase Participants received placebo intranasal spray for 2 episodes of breakthrough pain.
Overall Number of Participants Analyzed 15 15
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
PID at 5 minutes
1.3
(0.72 to 1.89)
0.8
(0.18 to 1.51)
PID at 30 minutes
3.0
(2.03 to 3.88)
1.8
(0.79 to 2.88)
PID at 60 minutes
3.3
(2.34 to 4.17)
2.2
(1.17 to 3.27)
4.Secondary Outcome
Title Efficacy Phase: Sum of Pain Intensity Differences (SPID0-60 and SPID0-30) Derived From PI Scores
Hide Description

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.

Time Frame During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Phase, Full Analysis Set
Arm/Group Title Intranasal Fentanyl Spray (INFS) Placebo
Hide Arm/Group Description:
In the Efficacy phase participants received 400 μg INFS for 6 episodes of breakthrough pain.
In the Efficacy Phase Participants received placebo intranasal spray for 2 episodes of breakthrough pain.
Overall Number of Participants Analyzed 15 15
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
SPID30
0.6
(0.38 to 0.90)
0.4
(0.09 to 0.67)
SPID60
0.7
(0.46 to 1.04)
0.5
(0.13 to 0.77)
5.Secondary Outcome
Title Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 1, 2 or 3 Point Reduction in Pain Intensity
Hide Description 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".
Time Frame During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Phase, Full Analysis Set
Arm/Group Title Intranasal Fentanyl Spray (INFS) Placebo
Hide Arm/Group Description:
In the Efficacy phase participants received 400 μg INFS for 6 episodes of breakthrough pain.
In the Efficacy Phase Participants received placebo intranasal spray for 2 episodes of breakthrough pain.
Overall Number of Participants Analyzed 15 15
Overall Number of Units Analyzed
Type of Units Analyzed: Breakthrough pain episodes
88 29
Measure Type: Number
Unit of Measure: proportion of breakthrough pain episodes
≥ 1 point reduction in PI at 5 minutes 0.61 0.45
≥ 1 point reduction in PI at 10 minutes 0.74 0.55
≥ 1 point reduction in PI at 30 minutes 0.81 0.66
≥ 1 point reduction in PI at 60 minutes 0.86 0.69
≥ 2 point reduction in PI at 5 minutes 0.33 0.24
≥ 2 point reduction in PI at 10 minutes 0.51 0.31
≥ 2 point reduction in PI at 30 minutes 0.60 0.41
≥ 2 point reduction in PI at 60 minutes 0.65 0.48
≥ 3 point reduction in PI at 5 minutes 0.18 0.17
≥ 3 point reduction in PI at 10 minutes 0.32 0.24
≥ 3 point reduction in PI at 30 minutes 0.45 0.34
≥ 3 point reduction in PI at 60 minutes 0.50 0.48
6.Secondary Outcome
Title Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 33% or 50% Reduction in Pain Intensity
Hide Description 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".
Time Frame During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Phase, Full Analysis Set
Arm/Group Title Intranasal Fentanyl Spray (INFS) Placebo
Hide Arm/Group Description:
In the Efficacy phase participants received 400 μg INFS for 6 episodes of breakthrough pain.
In the Efficacy Phase Participants received placebo intranasal spray for 2 episodes of breakthrough pain.
Overall Number of Participants Analyzed 15 15
Overall Number of Units Analyzed
Type of Units Analyzed: Breakthrough pain episodes
88 29
Measure Type: Number
Unit of Measure: proportion of breakthrough pain episodes
> 33% reduction in PI at 5 minutes 0.23 0.17
> 33% reduction in PI at 10 minutes 0.44 0.24
> 33% reduction in PI at 30 minutes 0.55 0.34
> 33% reduction in PI at 60 minutes 0.58 0.48
≥ 50% reduction in PI at 5 minutes 0.11 0.07
≥ 50% reduction in PI at 10 minutes 0.31 0.21
≥ 50% reduction in PI at 30 minutes 0.49 0.31
≥ 50% reduction in PI at 60 minutes 0.52 0.34
7.Secondary Outcome
Title Efficacy Phase: General Impression (GI) Score at 60 Minutes After First Dose
Hide Description

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:

  • 0 =poor;
  • 1 =fair;
  • 2 =good;
  • 3 =very good;
  • 4 =excellent.
Time Frame During the efficacy phase (II), at each episode of breakthrough pain, 60 minutes after first dose of study drug.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Phase, Full Analysis Set
Arm/Group Title Intranasal Fentanyl Spray (INFS) Placebo
Hide Arm/Group Description:
In the Efficacy phase participants received 400 μg INFS for 6 episodes of breakthrough pain.
In the Efficacy Phase Participants received placebo intranasal spray for 2 episodes of breakthrough pain.
Overall Number of Participants Analyzed 15 15
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
1.9
(1.41 to 2.47)
1.1
(0.52 to 1.71)
8.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description 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.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Titration Phase Efficacy Phase Tolerability Phase
Hide Arm/Group Description:
All participants were step-wise titrated to an effective dose of 50, 100, 200 or 400 μg INFS in the Titration 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.
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.
Overall Number of Participants Analyzed 45 15 31
Measure Type: Number
Unit of Measure: participants
Any AE 23 6 22
Any AE reported as related to treatment 14 4 6
Non-serious adverse events 22 5 17
Serious adverse events 2 2 8
Deaths 2 1 5
Severe adverse events 2 2 7
AEs leading to withdrawal 2 2 3
AEs possibly associated with nasal intolerability 2 0 6
AEs with an onset within 30 minutes of first dose 11 3 5
Time Frame 12 weeks
Adverse Event Reporting Description 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.
 
Arm/Group Title Titration Phase Efficacy Phase Tolerability Phase
Hide Arm/Group Description 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.
All-Cause Mortality
Titration Phase Efficacy Phase Tolerability Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Titration Phase Efficacy Phase Tolerability Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/45 (4.44%)   2/15 (13.33%)   8/31 (25.81%) 
Cardiac disorders       
Cardiovascular insufficiency  1  0/45 (0.00%)  1/15 (6.67%)  0/31 (0.00%) 
General disorders       
Device occlusion  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Disease progression  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Hepatobiliary disorders       
Jaundice  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Injury, poisoning and procedural complications       
Femur fracture  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Malignant neoplasm progression  1  1/45 (2.22%)  0/15 (0.00%)  2/31 (6.45%) 
Metastases to lung  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Psychiatric disorders       
Depression  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Renal and urinary disorders       
Azotaemia  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Respiratory, thoracic and mediastinal disorders       
Respiratory depression  1  0/45 (0.00%)  1/15 (6.67%)  1/31 (3.23%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Titration Phase Efficacy Phase Tolerability Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/45 (48.89%)   5/15 (33.33%)   17/31 (54.84%) 
Blood and lymphatic system disorders       
Anaemia  1  0/45 (0.00%)  0/15 (0.00%)  2/31 (6.45%) 
Cardiac disorders       
Tachycardia  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Gastrointestinal disorders       
Abdominal discomfort  1  0/45 (0.00%)  1/15 (6.67%)  0/31 (0.00%) 
Abdominal hernia  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Abdominal pain upper  1  1/45 (2.22%)  1/15 (6.67%)  2/31 (6.45%) 
Constipation  1  1/45 (2.22%)  0/15 (0.00%)  1/31 (3.23%) 
Diarrhoea  1  3/45 (6.67%)  0/15 (0.00%)  0/31 (0.00%) 
Dry mouth  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Nausea  1  10/45 (22.22%)  1/15 (6.67%)  8/31 (25.81%) 
Vomiting  1  3/45 (6.67%)  1/15 (6.67%)  4/31 (12.90%) 
General disorders       
Asthenia  1  1/45 (2.22%)  0/15 (0.00%)  1/31 (3.23%) 
Discomfort  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Face oedema  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Fatigue  1  3/45 (6.67%)  1/15 (6.67%)  1/31 (3.23%) 
General physical health deterioration  1  2/45 (4.44%)  0/15 (0.00%)  1/31 (3.23%) 
Irritability  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Pyrexia  1  1/45 (2.22%)  0/15 (0.00%)  2/31 (6.45%) 
Infections and infestations       
Bronchitis  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Influenza  1  1/45 (2.22%)  0/15 (0.00%)  1/31 (3.23%) 
Nasopharyngitis  1  0/45 (0.00%)  0/15 (0.00%)  2/31 (6.45%) 
Injury, poisoning and procedural complications       
Procedural dizziness  1  0/45 (0.00%)  1/15 (6.67%)  0/31 (0.00%) 
Metabolism and nutrition disorders       
Cachexia  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Decreased appetite  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Dehydration  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Musculoskeletal and connective tissue disorders       
Joint stiffness  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Joint swelling  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Muscle rigidity  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Musculoskeletal pain  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Osteoarthritis  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Malignant neoplasm progression  1  0/45 (0.00%)  0/15 (0.00%)  2/31 (6.45%) 
Nervous system disorders       
Dizziness  1  8/45 (17.78%)  2/15 (13.33%)  4/31 (12.90%) 
Headache  1  1/45 (2.22%)  0/15 (0.00%)  3/31 (9.68%) 
Horner's syndrome  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Hypoaesthesia  1  0/45 (0.00%)  0/15 (0.00%)  2/31 (6.45%) 
Paraesthesia  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Sedation  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Somnolence  1  2/45 (4.44%)  0/15 (0.00%)  0/31 (0.00%) 
Tremor  1  1/45 (2.22%)  0/15 (0.00%)  1/31 (3.23%) 
Psychiatric disorders       
Anxiety  1  0/45 (0.00%)  0/15 (0.00%)  2/31 (6.45%) 
Emotional distress  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Insomnia  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Sleep disorder  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Renal and urinary disorders       
Dysuria  1  1/45 (2.22%)  0/15 (0.00%)  0/31 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dry throat  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Dyspnoea  1  0/45 (0.00%)  0/15 (0.00%)  2/31 (6.45%) 
Epistaxis  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Hiccups  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Nasal congestion  1  1/45 (2.22%)  0/15 (0.00%)  1/31 (3.23%) 
Nasal discomfort  1  1/45 (2.22%)  0/15 (0.00%)  3/31 (9.68%) 
Nasal dryness  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Nasal oedema  1  0/45 (0.00%)  0/15 (0.00%)  3/31 (9.68%) 
Nasal ulcer  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Skin and subcutaneous tissue disorders       
Hyperhidrosis  1  2/45 (4.44%)  0/15 (0.00%)  1/31 (3.23%) 
Pruritus  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Urticaria  1  0/45 (0.00%)  1/15 (6.67%)  0/31 (0.00%) 
Vascular disorders       
Hot flush  1  1/45 (2.22%)  0/15 (0.00%)  1/31 (3.23%) 
Superior vena cava syndrome  1  0/45 (0.00%)  0/15 (0.00%)  1/31 (3.23%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01429051     History of Changes
Other Study ID Numbers: FT-1301-032-SP
2010-021096-85 ( EudraCT Number )
U1111-1133-6364 ( Registry Identifier: WHO )
2011/776 ( Registry Identifier: REK )
First Submitted: September 1, 2011
First Posted: September 5, 2011
Results First Submitted: January 1, 2014
Results First Posted: March 26, 2014
Last Update Posted: March 26, 2014