Clinical Trial Results:
A phase 2, randomised, double-blind, placebo-controlled, crossover study to evaluate the effects of a topical pentosan polysulphate sodium (PPS) formulation in subjects with seasonal allergic rhinitis
Summary
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EudraCT number |
2016-003341-28 |
Trial protocol |
SE |
Global end of trial date |
22 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Apr 2018
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First version publication date |
07 Apr 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PARA_003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Paradigm Biopharmaceuticals
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Sponsor organisation address |
Level 2, 517 Flinders Lane, Melbourne, Australia,
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Public contact |
Claire Kaufman, Chief Operations Officer, Paradigm Biopharmaceuticals, +61 413 421 160, ckaufman@paradigmbiopharma.com
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Scientific contact |
Claire Kaufman, Chief Operations Officer, Paradigm Biopharmaceuticals, +61 413 421 160, ckaufman@paradigmbiopharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Nov 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Mar 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective was to assess the effect of a topical Pentosan polysulphate sodium formulation on post-challenge nasal symptoms using an allergen challenge model in subjects with seasonal allergic rhinitis.
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Protection of trial subjects |
Subjects attended a follow-up visit 1 to 2 weeks after the last day of the second treatment period. Additional physical and nasal examinations and measurements of vital signs could be performed if clinically indicated.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
21 Nov 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
40
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
All subjects were recruited at a single site. Informed consent and screening were on the same day. The first subject provided informed consent and was screened on 21 November 2016. The last subject provided informed consent and was screened on 18 January 2017. | |||||||||||||||
Pre-assignment
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Screening details |
Forty-five (45) subjects were screened, of whom 40 were randomized to one of the two treatment arms. There were 5 screening failures, all of which were because exclusion criterion #13 (APTT value outside the normal range at screening) was met. | |||||||||||||||
Period 1
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Period 1 title |
Baseline period (screening to day -1)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||||||||
Blinding implementation details |
The Sponsor was also blinded to treatment arm allocation.
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Arms
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Arm title
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Baseline period | |||||||||||||||
Arm description |
All enrolled subjects | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
Pentosan polysulphate sodium
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
Pentosan polysulphate sodium was provided in a 20 mL silicone lined class 1 glass bottle, closed with a cartridge pump system nasal pump device. NOTE: Pentosan polysulphate sodium was not administered during the baseline period.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
The placebo formulation consisted of the Pentosan polysulphate sodium formulation vehicle, adjusted to isotonicity with NaCl. Placebo was provided in a 20 mL silicone lined class 1 glass bottle, closed with a cartridge pump system nasal pump device. NOTE: Placebo was not administered during the baseline period.
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Period 2
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Period 2 title |
Treatment period (days 1 to 14)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||||||||
Blinding implementation details |
The Sponsor was also blinded to treatment arm allocation.
The placebo and formulations were identical in appearance and nasal feel. The study site was given envelopes (one per subject) containing each subject's treatment allocation. These envelopes were held in a secure location. In a medical emergency requiring knowledge of the study drug, the envelope for that subject could be opened to determine their treatment allocation (while maintaining the blinding for all other subjects).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Pentosan polysulphate sodium then Placebo | |||||||||||||||
Arm description |
Subjects received Pentosan polysulphate sodium (80 mg/day) during treatment period 1 and Placebo during treatment period 2. Subjects received IMP using 2 sprays per nostril twice daily. Nasal symptoms and PNIF ( Peak Nasal Inspiratory Flow) were assessed before each dose. During the last 7 days of each treatment period, an individualised allergen challenge was administered after the morning dose of IMP. Nasal symptoms were assessed 10 minutes after the allergen challenge. | |||||||||||||||
Arm type |
Experimental and Placebo | |||||||||||||||
Investigational medicinal product name |
Pentosan polysulphate sodium
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Investigational medicinal product code |
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Other name |
PPS, Rhinosul®
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
Pentosan polysulphate sodium was provided in a 20 mL silicone lined class 1 glass bottle, closed with a cartridge pump system nasal pump device. Subjects received Pentosan polysulphate sodium as 2 equal daily doses for 14 days. They self-administered Pentosan polysulphate sodium each morning and evening. For each morning or evening dose, subjects administered 1 spray (100 µL) of Pentosan polysulphate sodium to each nostril, waited 2 minutes, and then administered a second spray to each nostril. The concentration of Pentosan polysulphate sodium was 100 mg/mL and the total dose per day was 80 mg.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
The placebo formulation consisted of the Pentosan polysulphate sodium formulation vehicle, adjusted to isotonicity with NaCl. Placebo was provided in a 20 mL silicone lined class 1 glass bottle, closed with a cartridge pump system nasal pump device. Subjects received Placebo for 14 days. They self-administered Placebo each morning and evening. For each morning or evening dose, subjects administered 1 spray (100 µL) of Placebo to each nostril, waited 2 minutes, and then administered a second spray to each nostril.
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Arm title
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Placebo then Pentosan polysulphate sodium | |||||||||||||||
Arm description |
Subjects received Placebo during treatment period 1 and Pentosan polysulphate sodium (80 mg/day) during treatment period 2. Subjects received IMP using 2 sprays per nostril twice daily. Nasal symptoms and PNIF ( Peak Nasal Inspiratory Flow) were assessed before each dose. During the last 7 days of each treatment period, an individualised allergen challenge was administered after the morning dose of IMP. Nasal symptoms were assessed 10 minutes after the allergen challenge. | |||||||||||||||
Arm type |
Experimental and Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
See description for Pentosan polysulphate sodium then Placebo arm
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Investigational medicinal product name |
Pentosan polysulphate sodium
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Investigational medicinal product code |
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Other name |
PPS, Rhinosul®
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
See description for Pentosan polysulphate sodium then Placebo arm
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Baseline characteristics reporting groups
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Reporting group title |
Baseline period
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Reporting group description |
All enrolled subjects | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
PPROT, Pentosan polysulphate sodium
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Pentosan polysulphate sodium data for all randomised subjects who (i) were deemed to have no major protocol violations that could interfere with the primary objective of the study and (ii) took at least 22 of 28 full doses of the study drug, including all 3 morning doses and the first 2 evening doses during the last 3 days of allergen challenge (treatment days 12 to 14), according to the diary cards, during both treatment periods
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Subject analysis set title |
PPROT, Placebo
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Placebo data for all randomised subjects who (i) were deemed to have no major protocol violations that could interfere with the primary objective of the study and (ii) took at least 22 of 28 full doses of the study drug, including all 3 morning doses and the first 2 evening doses during the last 3 days of allergen challenge (treatment days 12 to 14), according to the diary cards, during both treatment periods
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Subject analysis set title |
FAS, Pentosan polysulphate sodium
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Pentosan polysulphate sodium data for all randomised subjects who (i) took at least 1 dose of study drug, (ii) received at least 1 allergen challenge and (iii) had at least 1 post-baseline assessment of any efficacy variable
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Subject analysis set title |
FAS, Placebo
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Placebo data for all randomised subjects who (i) took at least 1 dose of study drug, (ii) received at least 1 allergen challenge and (iii) had at least 1 post-baseline assessment of any efficacy variable
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Subject analysis set title |
Safety Set, Pentosan polysulphate sodium then Placebo arm
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomised subjects in the Pentosan polysulphate sodium then Placebo arm who received at least 1 dose of study drug
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Subject analysis set title |
Safety Set, Placebo then Pentosan polysulphate sodium arm
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomised subjects in the Placebo then Pentosan polysulphate sodium arm who received at least 1 dose of study drug
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End points reporting groups
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Reporting group title |
Baseline period
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Reporting group description |
All enrolled subjects | ||
Reporting group title |
Pentosan polysulphate sodium then Placebo
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Reporting group description |
Subjects received Pentosan polysulphate sodium (80 mg/day) during treatment period 1 and Placebo during treatment period 2. Subjects received IMP using 2 sprays per nostril twice daily. Nasal symptoms and PNIF ( Peak Nasal Inspiratory Flow) were assessed before each dose. During the last 7 days of each treatment period, an individualised allergen challenge was administered after the morning dose of IMP. Nasal symptoms were assessed 10 minutes after the allergen challenge. | ||
Reporting group title |
Placebo then Pentosan polysulphate sodium
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Reporting group description |
Subjects received Placebo during treatment period 1 and Pentosan polysulphate sodium (80 mg/day) during treatment period 2. Subjects received IMP using 2 sprays per nostril twice daily. Nasal symptoms and PNIF ( Peak Nasal Inspiratory Flow) were assessed before each dose. During the last 7 days of each treatment period, an individualised allergen challenge was administered after the morning dose of IMP. Nasal symptoms were assessed 10 minutes after the allergen challenge. | ||
Subject analysis set title |
PPROT, Pentosan polysulphate sodium
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Pentosan polysulphate sodium data for all randomised subjects who (i) were deemed to have no major protocol violations that could interfere with the primary objective of the study and (ii) took at least 22 of 28 full doses of the study drug, including all 3 morning doses and the first 2 evening doses during the last 3 days of allergen challenge (treatment days 12 to 14), according to the diary cards, during both treatment periods
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Subject analysis set title |
PPROT, Placebo
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Placebo data for all randomised subjects who (i) were deemed to have no major protocol violations that could interfere with the primary objective of the study and (ii) took at least 22 of 28 full doses of the study drug, including all 3 morning doses and the first 2 evening doses during the last 3 days of allergen challenge (treatment days 12 to 14), according to the diary cards, during both treatment periods
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Subject analysis set title |
FAS, Pentosan polysulphate sodium
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Pentosan polysulphate sodium data for all randomised subjects who (i) took at least 1 dose of study drug, (ii) received at least 1 allergen challenge and (iii) had at least 1 post-baseline assessment of any efficacy variable
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Subject analysis set title |
FAS, Placebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Placebo data for all randomised subjects who (i) took at least 1 dose of study drug, (ii) received at least 1 allergen challenge and (iii) had at least 1 post-baseline assessment of any efficacy variable
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Subject analysis set title |
Safety Set, Pentosan polysulphate sodium then Placebo arm
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomised subjects in the Pentosan polysulphate sodium then Placebo arm who received at least 1 dose of study drug
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Subject analysis set title |
Safety Set, Placebo then Pentosan polysulphate sodium arm
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomised subjects in the Placebo then Pentosan polysulphate sodium arm who received at least 1 dose of study drug
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End point title |
Mean post-challenge TNSS over the last 3 days of allergen challenge | ||||||||||||||||||||
End point description |
Nasal symptoms were monitored approximately 10 minutes after allergen challenge. TNSS (total nasal symptom score) was calculated as the sum of the scores for the following nasal symptoms, each scored on a scale from 1 to 3: (i) nasal secretion, (ii) nasal congestion and (iii) sneezing or nasal itching (whichever was more severe). TNSS has a value of 0 to 9.
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End point type |
Primary
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End point timeframe |
Last 3 days of allergen challenge (treatment days 12 to 14)
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Statistical analysis title |
ANOVA, PPROT | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
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Comparison groups |
PPROT, Pentosan polysulphate sodium v PPROT, Placebo
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||||||||||
P-value |
= 0.5759 [2] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [1] - Comparison of Pentosan polysulphate sodium versus Placebo in the 37 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 37. [2] - Not significant |
|||||||||||||||||||||
Statistical analysis title |
ANOVA, FAS | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
FAS, Pentosan polysulphate sodium v FAS, Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [3] | ||||||||||||||||||||
P-value |
= 0.6083 [4] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [3] - Comparison of Pentosan polysulphate sodium versus Placebo in the 39 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 39. [4] - Not significant |
|
|||||||||||||||||||||
End point title |
Mean morning TNSS over the last 3 days of allergen challenge | ||||||||||||||||||||
End point description |
Nasal symptoms were monitored within 30 minutes of waking. TNSS was calculated as the sum of the scores for (i) nasal secretion, (ii) nasal congestion and (iii) sneezing or nasal itching (whichever was more severe).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Last 3 days of allergen challenge (treatment days 12 to 14)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
ANOVA, PPROT | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
PPROT, Pentosan polysulphate sodium v PPROT, Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
74
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [5] | ||||||||||||||||||||
P-value |
= 0.8953 [6] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [5] - Comparison of Pentosan polysulphate sodium versus Placebo in the 37 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 37. [6] - Not significant |
|||||||||||||||||||||
Statistical analysis title |
ANOVA, FAS | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
FAS, Pentosan polysulphate sodium v FAS, Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [7] | ||||||||||||||||||||
P-value |
= 0.7166 [8] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [7] - Comparison of Pentosan polysulphate sodium versus Placebo in the 39 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 39. [8] - Not significant |
|
|||||||||||||||||||||
End point title |
Mean evening TNSS over the last 3 days of allergen challenge | ||||||||||||||||||||
End point description |
Nasal symptoms were monitored between 20:00 and 24:00. TNSS was calculated as the sum of the scores for (i) nasal secretion, (ii) nasal congestion and (iii) sneezing or nasal itching (whichever was more severe).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Last 3 days of allergen challenge (treatment days 12 to 14)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
ANOVA, PPROT | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
PPROT, Pentosan polysulphate sodium v PPROT, Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
74
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [9] | ||||||||||||||||||||
P-value |
= 0.1526 [10] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [9] - Comparison of Pentosan polysulphate sodium versus Placebo in the 37 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 37. [10] - Not significant |
|||||||||||||||||||||
Statistical analysis title |
ANOVA, FAS | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
FAS, Pentosan polysulphate sodium v FAS, Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [11] | ||||||||||||||||||||
P-value |
= 0.2075 [12] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [11] - Comparison of Pentosan polysulphate sodium versus Placebo in the 39 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 39. [12] - Not significant |
|
|||||||||||||||||||||
End point title |
Mean post-challenge PNIF over the last 3 days of allergen challenge | ||||||||||||||||||||
End point description |
Subjects measured PNIF (peak nasal inspiratory flow) using a flow meter equipped with a facial mask immediately after post-allergen challenge monitoring of nasal symptoms. Subjects recorded 3 PNIF measurements, the highest of which was used in the analyses.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Last 3 days of allergen challenge (treatment days 12 to 14)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
ANOVA, PPROT | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
PPROT, Placebo v PPROT, Pentosan polysulphate sodium
|
||||||||||||||||||||
Number of subjects included in analysis |
74
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [13] | ||||||||||||||||||||
P-value |
= 0.3467 [14] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [13] - Comparison of Pentosan polysulphate sodium versus Placebo in the 37 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 37. [14] - Not significant |
|||||||||||||||||||||
Statistical analysis title |
ANOVA, FAS | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
FAS, Pentosan polysulphate sodium v FAS, Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [15] | ||||||||||||||||||||
P-value |
= 0.2687 [16] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [15] - Comparison of Pentosan polysulphate sodium versus Placebo in the 39 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 39. [16] - Not significant |
|
|||||||||||||||||||||
End point title |
Mean morning PNIF over the last 3 days of allergen challenge | ||||||||||||||||||||
End point description |
Subjects measured PNIF immediately after morning monitoring of nasal symptoms. Subjects recorded 3 PNIF measurements, the highest of which was used in the analyses.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Last 3 days of allergen challenge (treatment days 12 to 14)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
ANOVA, PPROT | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
PPROT, Placebo v PPROT, Pentosan polysulphate sodium
|
||||||||||||||||||||
Number of subjects included in analysis |
74
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [17] | ||||||||||||||||||||
P-value |
= 0.7048 [18] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [17] - Comparison of Pentosan polysulphate sodium versus Placebo in the 37 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 37. [18] - Not significant |
|||||||||||||||||||||
Statistical analysis title |
ANOVA, FAS | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
FAS, Placebo v FAS, Pentosan polysulphate sodium
|
||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [19] | ||||||||||||||||||||
P-value |
= 0.5238 [20] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [19] - Comparison of Pentosan polysulphate sodium versus Placebo in the 39 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 39. [20] - Not significant |
|
|||||||||||||||||||||
End point title |
Mean evening PNIF over the last 3 days of allergen challenge | ||||||||||||||||||||
End point description |
Subjects measured PNIF immediately after evening monitoring of nasal symptoms. Subjects recorded 3 PNIF measurements, the highest of which was used in the analyses.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Last 3 days of allergen challenge (treatment days 12 to 14)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
ANOVA, PPROT | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
PPROT, Placebo v PPROT, Pentosan polysulphate sodium
|
||||||||||||||||||||
Number of subjects included in analysis |
74
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [21] | ||||||||||||||||||||
P-value |
= 0.0262 [22] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [21] - Comparison of Pentosan polysulphate sodium versus Placebo in the 37 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 37. [22] - Significant difference in favour of Placebo |
|||||||||||||||||||||
Statistical analysis title |
ANOVA, FAS | ||||||||||||||||||||
Statistical analysis description |
ANOVA model with subject, treatment period and treatment as fixed effects
|
||||||||||||||||||||
Comparison groups |
FAS, Placebo v FAS, Pentosan polysulphate sodium
|
||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority [23] | ||||||||||||||||||||
P-value |
= 0.0177 [24] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Notes [23] - Comparison of Pentosan polysulphate sodium versus Placebo in the 39 subjects with data for both Pentosan polysulphate sodium and Placebo. Note: Number of subjects included in analysis = 39. [24] - Significant difference in favour of Placebo |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From signing of informed consent at Visit 1 (screening) to completion of the final study visit
|
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Adverse event reporting additional description |
AEs elicited with non-leading questions or directly observed or spontaneously volunteered by subjects were reported. Subjects were asked to telephone the study site to report any AEs that occurred in the week following Visit 1, and to record AEs occurring between visits on diary cards.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
|
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Reporting groups
|
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Reporting group title |
Pentosan polysulphate sodium treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Adverse events that occurred in the Safety Set in relation to Pentosan polysulphate sodium treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo treatment
|
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Reporting group description |
Adverse events that occurred in the Safety Set in relation to Placebo treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
22 Mar 2017 |
A preliminary review of blinded data (prior to finalisation of the statistical analysis plan and database lock) revealed that 15/40 subjects would be excluded from the per-protocol set, as defined in the study protocol, because they failed to take “all 6 doses [of IMP] during the last 3 days of allergen challenge (treatment days 12 to 14; according to the diary cards), during both treatment periods”. With one exception, all subjects who failed to take all of these 6 doses of IMP failed to take the very last dose and only that dose. This last dose was scheduled to be taken after the final assessments (of nasal symptoms and peak nasal inspiratory flow) on the last day of the treatment period. Therefore, failure to take the final evening dose had no implications for the efficacy analyses. To increase the validity of the efficacy analyses, which use the per-protocol set as the primary analysis population, the per-protocol set was redefined as: "All randomised subjects who (i) are deemed to have no major protocol violations that could interfere with the primary objective of this study and (ii) took at least 22 of the 28 doses of the study medication, including all 3 morning doses and the first 2 evening doses during the last 3 days of allergen challenge (treatment days 12 to 14) according to the diary cards, during both treatment periods." NOTE: The actual date of the amendment is 24 April 2017 (i.e. after 22 March 2017, the global end of trial date). |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |