Trial Outcomes & Findings for Dymista Allergen Chamber - Onset of Action Study (NCT NCT04652245)

Last Updated: 2023-03-23

Results Overview

FDA guideline defines onset of action as the first time point after initiation of treatment when the product demonstrated a greater change from baseline compared to placebo which proved durable. In this study, the first significant difference to placebo of TNSS was observed at 5 minutes time point (= onset of action). The TNSS is comprised of 4 symptoms from the nose, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TNSS contributes to a score ranging from 0 - 12.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

216 participants

Primary outcome timeframe

0 to 4 hours post application

Results posted on

2023-03-23

Participant Flow

Treatment Administration Period 1: Treatment A or B at medical clinic, duration: 1 day; Wash out Period at home, duration: at least 14 days; Treatment Administration Period 2: Treatment B or A at medical clinic, duration: 1 day;

Participant milestones

Participant milestones
Measure	Treatment A (Dymista) and Treatment B (Placebo), Separated by at Least 14 Days of Wash-out Period Fixed drug combination of Azelastine hydrochloride 137 μg / Fluticasone propionate 50 μg nasal spray and Placebo nasal spray Treatment A (Dymista): Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 3: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 3 Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 5: Single dose, one spray in each nostril of Placebo nasal spray at Visit 5	Treatment B (Placebo) and Treatment A (Dymista), Separated by at Least 14 Days of Wash-out Period Placebo nasal spray and Fixed drug combination of Azelastine hydrochloride 137 μg / Fluticasone propionate 50 μg nasal spray Treatment A (Dymista): Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 5: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 5 Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 3: Single dose, one spray in each nostril of Placebo nasal spray, at Visit 3
Treatment Administration Period 1 STARTED	108	108
Treatment Administration Period 1 COMPLETED	108	108
Treatment Administration Period 1 NOT COMPLETED	0	0
Wash-Out Period STARTED	108	108
Wash-Out Period COMPLETED	108	104
Wash-Out Period NOT COMPLETED	0	4
Treatment Administration Period 2 STARTED	108	104
Treatment Administration Period 2 COMPLETED	108	104
Treatment Administration Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment A (Dymista) and Treatment B (Placebo), Separated by at Least 14 Days of Wash-out Period Fixed drug combination of Azelastine hydrochloride 137 μg / Fluticasone propionate 50 μg nasal spray and Placebo nasal spray Treatment A (Dymista): Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 3: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 3 Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 5: Single dose, one spray in each nostril of Placebo nasal spray at Visit 5	Treatment B (Placebo) and Treatment A (Dymista), Separated by at Least 14 Days of Wash-out Period Placebo nasal spray and Fixed drug combination of Azelastine hydrochloride 137 μg / Fluticasone propionate 50 μg nasal spray Treatment A (Dymista): Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 5: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 5 Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 3: Single dose, one spray in each nostril of Placebo nasal spray, at Visit 3
Wash-Out Period Adverse Event	0	2
Wash-Out Period Withdrawal by Subject	0	2

Baseline Characteristics

Dymista Allergen Chamber - Onset of Action Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population (Crossover Design: Randomization to Dymista/Placebo or Placebo/Dymista) n=216 Participants Fixed drug combination of Azelastine hydrochloride 137 μg / Fluticasone propionate 50 μg nasal spray and Placebo nasal spray Treatment A (Dymista): Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 3 OR Visit 5: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 3 OR Visit 5. Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 5 OR Visit 3: Single dose, one spray in each nostril of Placebo nasal spray at Visit 5 OR Visit 3.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	216 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	114 Participants n=5 Participants
Sex: Female, Male Male	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	186 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race/Ethnicity, Customized Race, Customized · American Indian or Alaska Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Race, Customized · Asian	41 Participants n=5 Participants
Race/Ethnicity, Customized Race, Customized · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized Race, Customized · Black or African American	51 Participants n=5 Participants
Race/Ethnicity, Customized Race, Customized · White	117 Participants n=5 Participants
Race/Ethnicity, Customized Race, Customized · Other	6 Participants n=5 Participants
Region of Enrollment Canada	216 participants n=5 Participants
Height	169.7 cm STANDARD_DEVIATION 8.85 • n=5 Participants
Weight	79.38 kg STANDARD_DEVIATION 18.473 • n=5 Participants
BMI	27.50 kg/m^2 STANDARD_DEVIATION 5.817 • n=5 Participants

PRIMARY outcome

Timeframe: 0 to 4 hours post application

Population: FAS (Full Analysis Set) population includes all randomized patients, including subjects who received incorrect treatment, did not complete the study or did not comply to the protocol, and who were randomized but did not take any study medication. Overall number of Participants Analyzed means the number of participants for whom the respective TNSS value at 5 min post-dose was available.

Outcome measures

Outcome measures
Measure	Treatment A (Dymista), Cross-over Design, Time-point 5 Min Post-dose (Onset of Action) n=211 Participants Fixed drug combination of Azelastine hydrochloride 137 μg / Fluticasone propionate 50 μg nasal spray: Total Nasal Symptom Score (TNSS) difference to baseline after 5 min. post-dose Treatment A (Dymista) Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 3 OR Visit 5: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 3 OR Visit 5	Treatment B (Placebo), Cross-over Design, Time-point 5 Min Post-dose (Onset of Action) n=216 Participants Placebo nasal spray: Total Nasal Symptom Score (TNSS) difference to baseline after 5 min. post-dose Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 5 OR Visit 3: Single dose, one spray in each nostril of Placebo nasal spray at Visit 5 OR Visit 3
Change in Patient-assessed Instantaneous Total Nasal Symptom Score (TNSS) From Baseline Compared to Placebo	-1.37 score on a scale Standard Error 0.130	-1.04 score on a scale Standard Error 0.128

SECONDARY outcome

Timeframe: 0 to 4 hours post application

Population: FAS population includes all randomized patients, including subjects who received incorrect treatment, did not complete the study or did not comply to the protocol, and who were randomized but did not take any study medication. Overall number of Participants Analyzed means the number of participants for whom the respective TOSS value at 10 min post-dose was available.

FDA guideline defines onset of action as the first time point after initiation of treatment when the product demonstrated a greater change from baseline compared to placebo which proved durable. In this study, the first significant difference to placebo of TOSS was observed at 10 minutes time point (= onset of action). The TOSS is comprised of 3 symptoms from the eyes, each scored on a scale of 0 to 3 (0 = none and 3 = severe). The sum of the TOSS contributes to a score ranging from 0 - 9.

Outcome measures

Outcome measures
Measure	Treatment A (Dymista), Cross-over Design, Time-point 5 Min Post-dose (Onset of Action) n=211 Participants Fixed drug combination of Azelastine hydrochloride 137 μg / Fluticasone propionate 50 μg nasal spray: Total Nasal Symptom Score (TNSS) difference to baseline after 5 min. post-dose Treatment A (Dymista) Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 3 OR Visit 5: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 3 OR Visit 5	Treatment B (Placebo), Cross-over Design, Time-point 5 Min Post-dose (Onset of Action) n=215 Participants Placebo nasal spray: Total Nasal Symptom Score (TNSS) difference to baseline after 5 min. post-dose Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 5 OR Visit 3: Single dose, one spray in each nostril of Placebo nasal spray at Visit 5 OR Visit 3
Change in Patient-assessed Instantaneous Total Ocular Symptom Score (TOSS) From Baseline Compared to Placebo	-1.21 score on a scale Standard Error 0.104	-0.87 score on a scale Standard Error 0.103

Adverse Events

Treatment A (Dymista), Cross-over Design

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Treatment B (Placebo), Cross-over Design

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Not Dedicated to Any Treatment Group

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment A (Dymista), Cross-over Design n=212 participants at risk Fixed drug combination of Azelastine hydrochloride 137 μg / Fluticasone propionate 50 μg nasal spray: Treatment A (Dymista) Fixed drug combination of azelastine hydrochloride and fluticasone propionate nasal spray at Visit 3 OR Visit 5: Single dose, one spray in each nostril of Dymista nasal spray, approximately 137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate per actuation, at Visit 3 OR Visit 5	Treatment B (Placebo), Cross-over Design n=216 participants at risk Placebo nasal spray Treatment B (Placebo): Nasal spray with no active dose (Dymista vehicle) at Visit 5 OR Visit 3: Single dose, one spray in each nostril of Placebo nasal spray at Visit 5 OR Visit 3	Not Dedicated to Any Treatment Group n=216 participants at risk AEs not considered Treatment Emergent Adverse Events (not occurring in the period from administration of study medication until 5 days (120 h) thereafter)
General disorders Chest pain	0.00% 0/212 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.46% 1/216 • Number of events 1 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.00% 0/216 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.
Investigations Liver function test abnormal	0.00% 0/212 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.46% 1/216 • Number of events 1 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.00% 0/216 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.
Metabolism and nutrition disorders Glucose tolerance impaired	0.47% 1/212 • Number of events 1 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.00% 0/216 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.00% 0/216 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.
Nervous system disorders Dizziness	0.00% 0/212 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.93% 2/216 • Number of events 3 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.00% 0/216 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.
Nervous system disorders Headache	0.47% 1/212 • Number of events 1 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.93% 2/216 • Number of events 3 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	2.8% 6/216 • Number of events 6 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.
Investigations SARS-CoV-2 test positive	0.00% 0/212 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.00% 0/216 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.93% 2/216 • Number of events 2 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.
Nervous system disorders Migraine	0.00% 0/212 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.00% 0/216 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.	0.46% 1/216 • Number of events 1 • In this study, the adverse event (AE) collection period began at the signing of informed consent and continued until 5 to 7 days after the last dose of study medication. AEs occurring during this period needed to be reported. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product including an abnormal laboratory or physical findings, symptoms, or disease (new or exacerbated)) temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Subjects have been routinely queried in regard to the presence or absence of adverse events using open ended questions. Any AEs have been documented in the subject's eCRF.

Additional Information

Christine Kolb

Meda Pharma GmbH & Co. KG (A Viatris Company)

Phone: +496172888

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI is an employee of the CRO (Contract Research Organization) and disclosure restrictions are specified by the agreement with the CRO. CRO shall not publish any study results without the prior written express consent of the Sponsoring company. In the event that such consent is given the Sponsoring company shall have 90 days from receipt of the proposed publication to review and comment. The Sponsor can require changes to the publication and delay of 90 days to the publication.
Publication restrictions are in place

Restriction type: OTHER