Trial Outcomes & Findings for Effect of Veramyst and Olopatadine 0.2% Opthalmic Solution on Allergy Symptoms (NCT NCT01007253)

NCT ID: NCT01007253

Last Updated: 2013-07-17

Results Overview

After treatment, each participant was subjected to a diluent (control) challenge in one eye and was asked to rate 2 eye symptoms (watery and itchy) according to the following scale: 0=none, 1=mild, 2=moderate, 3=severe. The participant was then exposed to 3 doses of an antigen challenge and was asked to similarly rate severity of watery and itchy eye symptoms after each dose. Diluent challenge scores were subtracted from the scores recorded after each dose. This process was repeated in the other eye. The outcome is the total of the score differences (i.e. score after each dose subtracted by diluent challenge score) summed across doses, symptoms (watery and itchy), and eyes (left and right). Thus, each participant's total score is an integer value ranging from -36 to 36.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

21 participants

Primary outcome timeframe

50 minutes [duration of 3 nasal challenges and 2 washout periods]

Results posted on

2013-07-17

Participant Flow

Healthy patients age 18-50 completed an allergy questionnaire and underwent skin puncture testing for confirmation of allergy to grass or ragweed. Female subjects were given pregnancy tests. Patients who were eligible then underwent a screening nasal challenge with either grass or ragweed allergen depending on their skin test results and history.

After a 2-week washout period, 21 subjects who had positive screening challenge returned to the Nasal Physiology Laboratory where they were randomized to receive one of four treatment orderings in this four-way crossover study.

Participant milestones

Participant milestones
Measure
FF/PL, PL/OLO, FF/OLO, PL/PL
Each subject received a total of 4 weeks of treatment (1 week per treatment with 2 week washout period between treatments) in the following order: * fluticasone furoate (FF) nasal spray and PL eye drops (FF/PL) * PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (PL/OLO), * FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (FF/OLO), and * placebo (PL) nasal spray and PL eye drops (PL/PL).
PL/OLO, FF/OLO, PL/PL, FF/PL
Each subject received a total of 4 weeks of treatment (1 week per treatment with 2 week washout period between treatments) in the following order: * PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (PL/OLO), * FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (FF/OLO), * placebo (PL) nasal spray and PL eye drops (PL/PL), and * fluticasone furoate (FF) nasal spray and PL eye drops (FF/PL).
FF/OLO, PL/PL, FF/PL, PL/OLO
Each subject received a total of 4 weeks of treatment (1 week per treatment with 2 week washout period between treatments) in the following order: * FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (FF/OLO), * placebo (PL) nasal spray and PL eye drops (PL/PL), * fluticasone furoate (FF) nasal spray and PL eye drops (FF/PL), and * PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (PL/OLO).
PL/PL, FF/PL, PL/OLO, FF/OLO
Each subject received a total of 4 weeks of treatment (1 week per treatment with 2 week washout period between treatments) in the following order: * placebo (PL) nasal spray and PL eye drops (PL/PL), * fluticasone furoate (FF) nasal spray and PL eye drops (FF/PL), * PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (PL/OLO), and * FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (FF/OLO).
First Intervention
STARTED
6
5
5
5
First Intervention
COMPLETED
6
5
5
5
First Intervention
NOT COMPLETED
0
0
0
0
Washout Period (2 Weeks) # 1
STARTED
6
5
5
5
Washout Period (2 Weeks) # 1
COMPLETED
6
5
5
5
Washout Period (2 Weeks) # 1
NOT COMPLETED
0
0
0
0
Second Intervention
STARTED
6
5
5
5
Second Intervention
COMPLETED
6
5
5
5
Second Intervention
NOT COMPLETED
0
0
0
0
Washout Period (2 Weeks) # 2
STARTED
6
5
5
5
Washout Period (2 Weeks) # 2
COMPLETED
6
5
5
5
Washout Period (2 Weeks) # 2
NOT COMPLETED
0
0
0
0
Third Intervention
STARTED
6
5
5
5
Third Intervention
COMPLETED
6
5
5
5
Third Intervention
NOT COMPLETED
0
0
0
0
Washout Period (2 Weeks) # 3
STARTED
6
5
5
5
Washout Period (2 Weeks) # 3
COMPLETED
5
5
5
5
Washout Period (2 Weeks) # 3
NOT COMPLETED
1
0
0
0
Fourth Intervention
STARTED
5
5
5
5
Fourth Intervention
COMPLETED
5
5
5
5
Fourth Intervention
NOT COMPLETED
0
0
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
FF/PL, PL/OLO, FF/OLO, PL/PL
Each subject received a total of 4 weeks of treatment (1 week per treatment with 2 week washout period between treatments) in the following order: * fluticasone furoate (FF) nasal spray and PL eye drops (FF/PL) * PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (PL/OLO), * FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (FF/OLO), and * placebo (PL) nasal spray and PL eye drops (PL/PL).
PL/OLO, FF/OLO, PL/PL, FF/PL
Each subject received a total of 4 weeks of treatment (1 week per treatment with 2 week washout period between treatments) in the following order: * PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (PL/OLO), * FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (FF/OLO), * placebo (PL) nasal spray and PL eye drops (PL/PL), and * fluticasone furoate (FF) nasal spray and PL eye drops (FF/PL).
FF/OLO, PL/PL, FF/PL, PL/OLO
Each subject received a total of 4 weeks of treatment (1 week per treatment with 2 week washout period between treatments) in the following order: * FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (FF/OLO), * placebo (PL) nasal spray and PL eye drops (PL/PL), * fluticasone furoate (FF) nasal spray and PL eye drops (FF/PL), and * PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (PL/OLO).
PL/PL, FF/PL, PL/OLO, FF/OLO
Each subject received a total of 4 weeks of treatment (1 week per treatment with 2 week washout period between treatments) in the following order: * placebo (PL) nasal spray and PL eye drops (PL/PL), * fluticasone furoate (FF) nasal spray and PL eye drops (FF/PL), * PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (PL/OLO), and * FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution (FF/OLO).
Washout Period (2 Weeks) # 3
Physician Decision
1
0
0
0

Baseline Characteristics

Effect of Veramyst and Olopatadine 0.2% Opthalmic Solution on Allergy Symptoms

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Entire Study Population
n=21 Participants
Includes groups randomized to receive PL/PL first, FF/PL first, PL/OLO first, and FF/OLO first.
Age Continuous
31.1 years
STANDARD_DEVIATION 6.89 • n=5 Participants
Sex: Female, Male
Female
7 Participants
n=5 Participants
Sex: Female, Male
Male
14 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 50 minutes [duration of 3 nasal challenges and 2 washout periods]

Population: One subject was removed from the study due to upper respiratory tract infection, reducing the number of evaluable subjects from 21 to 20.

After treatment, each participant was subjected to a diluent (control) challenge in one eye and was asked to rate 2 eye symptoms (watery and itchy) according to the following scale: 0=none, 1=mild, 2=moderate, 3=severe. The participant was then exposed to 3 doses of an antigen challenge and was asked to similarly rate severity of watery and itchy eye symptoms after each dose. Diluent challenge scores were subtracted from the scores recorded after each dose. This process was repeated in the other eye. The outcome is the total of the score differences (i.e. score after each dose subtracted by diluent challenge score) summed across doses, symptoms (watery and itchy), and eyes (left and right). Thus, each participant's total score is an integer value ranging from -36 to 36.

Outcome measures

Outcome measures
Measure
PL/PL
n=20 Participants
placebo (PL) nasal spray and PL eye drops
FF/PL
n=20 Participants
fluticasone furoate (FF) nasal spray and PL eye drops
PL/OLO
n=20 Participants
PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
FF/OLO
n=20 Participants
FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
Total Eye Symptoms Score Difference
6 units on a scale
Interval 0.0 to 23.0
0 units on a scale
Interval -6.0 to 11.0
2.5 units on a scale
Interval 0.0 to 26.0
1.5 units on a scale
Interval -9.0 to 16.0

SECONDARY outcome

Timeframe: 50 minutes [duration of 3 nasal challenges and 2 washout periods]

Population: One subject was removed from the study due to upper respiratory tract infection, reducing the number of evaluable subjects from 21 to 20.

After treatment, each participant was subjected to a diluent (control) challenge in one nostril and was asked to rate nasal symptoms (congestion, rhinorrhea, and itchy nose/throat) according to the following scale: 0=none, 1=mild, 2=moderate, 3=severe. The participant was then exposed to 3 doses of an antigen challenge and was asked to similarly rate severity of nasal symptoms after each dose. Diluent challenge scores were subtracted from the scores recorded after each dose. This process was repeated in the other nostril. The outcome is the total number of score differences (i.e. score after each dose subtracted by diluent challenge score) summed across doses, symptoms (congestion, rhinorrhea, and itchy nose/throat), and nostrils (left and right). Thus, each participant's total score is an integer value ranging from -36 to 36.

Outcome measures

Outcome measures
Measure
PL/PL
n=20 Participants
placebo (PL) nasal spray and PL eye drops
FF/PL
n=20 Participants
fluticasone furoate (FF) nasal spray and PL eye drops
PL/OLO
n=20 Participants
PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
FF/OLO
n=20 Participants
FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
Total Nasal Symptoms Score Difference
17 units on a scale
Interval 6.0 to 34.0
10 units on a scale
Interval 3.0 to 31.0
9 units on a scale
Interval -2.0 to 35.0
9 units on a scale
Interval 0.0 to 26.0

SECONDARY outcome

Timeframe: 50 minutes [duration of 3 nasal challenges and 2 washout periods]

Population: One subject was removed from the study due to upper respiratory tract infection, reducing the number of evaluable subjects from 21 to 20.

Outcome measures

Outcome measures
Measure
PL/PL
n=20 Participants
placebo (PL) nasal spray and PL eye drops
FF/PL
n=20 Participants
fluticasone furoate (FF) nasal spray and PL eye drops
PL/OLO
n=20 Participants
PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
FF/OLO
n=20 Participants
FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
Total Number of Sneezes
10 sneezes
Interval 0.0 to 36.0
2.5 sneezes
Interval 0.0 to 50.0
2.5 sneezes
Interval 0.0 to 49.0
1.0 sneezes
Interval 0.0 to 16.0

SECONDARY outcome

Timeframe: 50 minutes [duration of 3 nasal challenges and 2 washout periods]

Population: One subject was removed from the study due to upper respiratory tract infection, reducing the number of evaluable subjects from 21 to 20.

Histamines are simple chemical substances produced by immune system cells when reacting to an antigen in response to foreign invaders like germs and bacteria. Histamine in nasal lavages was measured using a histamine enzyme immunoassay kit market by SPI-BIo, Bertin Pharma (Montigny le Bretonneux, France). The limit of detection of the assay is 0.4 nM, and levels below the detection limit were arbitrarily assigned a value of 0.2 nM. Samples that yielded values above the upper detection limit of the assay were diluted and reassayed. For each patient, histamine levels recorded after the diluent challenge were subtracted from histamine levels recorded after each of the three nasal challenges. These differences were added across challenges, yielding the total change in histamine level reported in this outcome for each patient.

Outcome measures

Outcome measures
Measure
PL/PL
n=20 Participants
placebo (PL) nasal spray and PL eye drops
FF/PL
n=20 Participants
fluticasone furoate (FF) nasal spray and PL eye drops
PL/OLO
n=20 Participants
PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
FF/OLO
n=20 Participants
FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
Change in Histamine Level (Across Nasal Challenges)
5.9 nM
Interval -2.0 to 203.0
0.3 nM
Interval -91.0 to 209.0
11.4 nM
Interval -9.0 to 435.0
3.4 nM
Interval -34.0 to 250.0

SECONDARY outcome

Timeframe: 50 minutes [duration of 3 nasal challenges and 2 washout periods]

Population: One subject was removed from the study due to upper respiratory tract infection, reducing the number of evaluable subjects from 21 to 20.

Tryptase is an enzyme that is released, along with histamine and other chemicals, from mast cells when they are activated, often as part of an allergic immune response. Tryptase in nasal lavages was measured using the ImmunoCap tryptase assay, by Phadia (Uppsala, Sweden). The limit of detection of the assay is 1.0 ng/mL, and levels below this value were arbitrarily assigned a value of 0.5 ng/mL. For each patient, tryptase levels recorded after the diluent challenge were subtracted from tryptase levels recorded after each of the three nasal challenges. These differences were added across challenges, yielding the total change in tryptase level reported in this outcome for each patient.

Outcome measures

Outcome measures
Measure
PL/PL
n=20 Participants
placebo (PL) nasal spray and PL eye drops
FF/PL
n=20 Participants
fluticasone furoate (FF) nasal spray and PL eye drops
PL/OLO
n=20 Participants
PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
FF/OLO
n=20 Participants
FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
Change in Tryptase Level (Across Nasal Challenges)
5 ng/mL
Interval 0.0 to 527.0
0 ng/mL
Interval 0.0 to 21.0
2 ng/mL
Interval 0.0 to 140.0
0 ng/mL
Interval 0.0 to 49.0

SECONDARY outcome

Timeframe: 50 minutes [duration of 3 nasal challenges and 2 washout periods]

Population: One subject was removed from the study due to upper respiratory tract infection, reducing the number of evaluable subjects from 21 to 20.

The percentage of eosinophils among white blood cells was determined under light microscopy at 1000x magnification, and the total number of eosinophils in each lavage was then calculated. The specimens that had no eosinophils identified on differential counting despite adequate cells on the smear were assigned a number that corresponded to the lowest number of eosinophils on a slide where the number could be counted. That number was 33 total eosinophils.

Outcome measures

Outcome measures
Measure
PL/PL
n=20 Participants
placebo (PL) nasal spray and PL eye drops
FF/PL
n=20 Participants
fluticasone furoate (FF) nasal spray and PL eye drops
PL/OLO
n=20 Participants
PL nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
FF/OLO
n=20 Participants
FF nasal spray and olopatadine (OLO) 0.2% ophthalmic solution
Total Number of Eosinophils
7883 eosinophils
Interval 33.0 to 2246440.0
238 eosinophils
Interval 33.0 to 604800.0
9606 eosinophils
Interval 33.0 to 953250.0
311 eosinophils
Interval 33.0 to 224000.0

Adverse Events

PL/PL

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

FF/PL

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

PL/OLO

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

FF/OLO

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Robert M. Naclerio, MD

The University of Chicago

Phone: (773) 702-1865

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place