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| ID | Type | Description | Link |
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| Doc ID: 3303796 |
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This is a randomized, multi-center, double-blind, placebo-controlled study evaluating the efficacy of pleconaril nasal spray in preventing asthma exacerbation and common cold symptoms in asthmatic participants exposed to picornavirus respiratory infections. Participants will be assigned treatment with pleconaril or placebo nasal spray for 7 days (14 doses). Participants will be followed for an additional 14 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pleconaril | Experimental | Participants will receive Pleconaril nasal spray 4 sprays per nostril twice daily (BID), 24 mg/day for 1 week during the Treatment Period for a total of 14 doses. |
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| Placebo | Placebo Comparator | Participants will receive placebo nasal spray 4 sprays per nostril BID for 1 week during the Treatment Period for a total of 14 doses. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pleconaril | Drug | Pleconaril nasal suspension is supplied in a bottle containing 120 actuations. Each actuation contains 1.5 mg of pleconaril. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Rhinovirus PCR-Positive Colds | The common cold was defined as moderate or severe rhinorrhea and at least one other cold symptom of moderate to severe intensity for at least 1 day, together with rhinovirus-positive polymerase chain reaction (PCR), after a participant had temporal exposure to an index case. PCR+ was defined as positive or equivocal outcome of the picornavirus test any time after randomization. | From time of exposure to index case to end of Follow-up Period (21 days) |
| Percentage of Participants With Asthma Exacerbations Together With Rhinovirus-Positive PCR | Asthma exacerbation was defined as a participant having one of the following:
PCR+ was defined as positive or equivocal outcome of the picornavirus test any time after randomization. | From time of exposure to index case to end of Follow-up Period (21 days) |
| Measure | Description | Time Frame |
|---|---|---|
| LS Mean Change From Baseline in the Asthma Control Questionnaire (ACQ) | The ACQ is a validated instrument containing 7 questions to assess asthma control which incorporates symptoms, beta-agonist use, and spirometry. Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of the 7 items and therefore ranges between 0 (well controlled) and 6 (extremely poorly controlled). The ACQ completed on the day of exposure was the Baseline ACQ. Pooled standard deviations (SDs) and least square (LS) means were calculated based on an analysis of variates (ANOVA) model. |
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Inclusion Criteria:
Must be ≥6 to ≤65 years of age, of either sex, and of any race, with a diagnosis of asthma at least 2 years prior to the Screening Visit.
Must have a history of two or more upper respiratory infection-induced asthma exacerbations in the past 24 months.
Must have been on a stable dose of any asthma medication (including immunotherapy) for at least 1 month prior to the Screening Visit.
Must have a pre-bronchodilator FEV1 ≥50% predicted at the Screening Visit, when all prohibited medications have been withheld for the specified interval.
If a reversibility test has not been performed within the previous 24 months, a participant, ≥17 years of age, must demonstrate an increase in absolute FEV1 of ≥12%, with an absolute volume increase of at least 200 mL. A participant <17 years of age, must demonstrate an increase in absolute FEV1 ≥12%.
Must cohabit with at least one other person (family member, roommate).
A participant (or the participant's legal representation) must be willing to give written informed consent and be able to adhere to dose and visit schedules.
Must be free of any clinically significant disease, other than asthma, which would interfere with study evaluation.
Must be in general good health, as confirmed by routine clinical and laboratory testing. All laboratory tests (Complete Blood Count, blood chemistries, and urinalysis) and elctrocardiograms must be within normal limits or clinically acceptable to the investigator/sponsor.
Female of childbearing potential must be using a medically acceptable, adequate form of birth control.
Exclusion Criteria:
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All enrolled participants were screened. After the screening visit and before randomization, participants received weekly phone calls and revisited the site once per month during a Pre-exposure Period until exposed to a household member with a cold (index case).
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants (Pre-randomization) | All participants on study prior to randomization. |
| FG001 | Pleconaril | Participants were randomized to receive Pleconaril nasal spray 4 sprays per nostril twice daily (BID), 24 mg/day for 1 week during the Treatment Period for a total of 14 doses. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Screening Period |
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| Placebo to Pleconaril | Drug | Placebo nasal suspension |
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| Baseline through the Final Visit (Day 21) |
| LS Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Pooled SDs and LS means were calculated based on an ANOVA model. | Baseline through the Final Visit (Day 21) |
| LS Mean Change From Baseline in Peak Expiratory Flow (PEF) in AM | PEF is a person's maximum speed of expiration as measured with a peak flow meter and was measured twice daily in the morning (AM) and evening (PM). Pooled SDs and LS means were calculated based on an ANOVA model. | Baseline through the Final Visit (Day 21) |
| LS Mean Change From Baseline in Peak Expiratory Flow (PEF) in PM | PEF is a person's maximum speed of expiration as measured with a peak flow meter and was measured twice daily in the morning (AM) and evening (PM). Pooled SDs and LS means were calculated based on an ANOVA model. | Baseline through the Final Visit (Day 21) |
| LS Mean Change From Baseline in Total Cold Symptom Score | Participants entered their cold symptoms into an e-diary twice daily beginning at the Screening Visit through completion of the study. The total cold symptom score was the sum of 6 scores for rhinorrhea, nasal congestion, cough, score throat, malaise, and myalgia. Each symptom is scored as follows: 0 = none-sign/symptom is not present, 1 = mild-sign/symptom noticeable but did not bother me or interfere with my normal daily activities/sleep, 2 = moderate- sign/symptom annoying and may have interfered with my normal daily activities/sleep, or 3 = severe-symptom very uncomfortable and interfered with most or all of my normal daily activities/sleep. The total score ranges from 0 to 18, with increasing scores reflecting more severe colds. Baseline values were defined as the average of the last seven assessments prior to randomization (before exposure to an index case). Pooled SDs and LS means were calculated based on an ANOVA model. | Baseline through the Final Visit (Day 21) |
| LS Mean Change From Baseline in Total Asthma Symptom Score | Participants entered their asthma symptoms into an e-diary twice daily beginning at the Screening Visit through completion of the study. The total asthma symptom score was the sum of 3 scores for wheeze, cough, and dyspnea. Each symptom is scored as follows: 0 = none-sign/symptom is not present, 1 = mild-sign/symptom noticeable but did not bother me or interfere with my normal daily activities/sleep, 2 = moderate- sign/symptom annoying and may have interfered with my normal daily activities/sleep, or 3 = severe-symptom very uncomfortable and interfered with most or all of my normal daily activities/sleep. The total score ranges from 0 to 9, with increasing scores reflecting more severe asthma. Baseline values were defined as the average of the last seven assessments prior to randomization (before exposure to an index case). Pooled SDs and LS means were calculated based on an ANOVA model. | Baseline through the Final Visit (Day 21) |
| LS Mean Change From Baseline in Short-acting Beta-Agonist (SABA) Rescue Medication Usage | SABAs such as albuterol were permitted during the study as rescue medication and required a 6-hour washout prior to each visit. Participants entered their asthma medication use into an e-diary twice daily beginning at the Screening Visit through completion of the study. The Baseline for diary symptoms was the average of the last seven assessments prior to Randomization. Pooled SDs and LS means were calculated based on an ANOVA model. | Baseline through the Final Visit (Day 21) |
| LS Mean Change From Baseline in Asthma-Related Sleep Interference | Participants entered their asthma-related changes in sleep into an e-diary once daily (in the morning) beginning at the Screening Visit through completion of the study. Changes from Baseline in asthma-related sleep interference were determined using the following question: How did cold and asthma symptoms interfere with your sleep? The question was scored as follows: 0 = None, no interference with sleep at all, 1 = Mild, not annoying or troublesome, adequate amount of sleep, 2 = Moderate, interfered somewhat with sleep, woke up a few times, average sleep, 3 = Severe, substantially interfered with sleep, poor sleep. The Baseline for diary symptoms was the average of the last seven assessments prior to Randomization. Pooled SDs and LS means were calculated based on an ANOVA model. | Baseline through the Final Visit (Day 21) |
| FG002 | Placebo | Participants were randomized to receive placebo nasal spray 4 sprays per nostril BID for 1 week during the Treatment Period for a total of 14 doses. |
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| Pre-exposure Period |
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| Treatment Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | Pleconaril | Participants received Pleconaril nasal spray 4 sprays per nostril twice daily (BID), 24 mg/day for 1 week during the Treatment Period for a total of 14 doses. |
| BG001 | Placebo | Participants received placebo nasal spray 4 sprays per nostril BID for 1 week during the Treatment Period for a total of 14 doses. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percentage of Participants With Rhinovirus PCR-Positive Colds | The common cold was defined as moderate or severe rhinorrhea and at least one other cold symptom of moderate to severe intensity for at least 1 day, together with rhinovirus-positive polymerase chain reaction (PCR), after a participant had temporal exposure to an index case. PCR+ was defined as positive or equivocal outcome of the picornavirus test any time after randomization. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some follow-up information. Randomized participants with no follow-up information were included in the number of participants assigned to each treatment group to determine rhinovirus cold. | Posted | Number | percentage of participants | From time of exposure to index case to end of Follow-up Period (21 days) |
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| Primary | Percentage of Participants With Asthma Exacerbations Together With Rhinovirus-Positive PCR | Asthma exacerbation was defined as a participant having one of the following:
PCR+ was defined as positive or equivocal outcome of the picornavirus test any time after randomization. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some follow-up information. Randomized participants with no follow-up information were included in the number of participants assigned to each treatment group to determine exacerbation. | Posted | Number | percentage of participants | From time of exposure to index case to end of Follow-up Period (21 days) |
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| Secondary | LS Mean Change From Baseline in the Asthma Control Questionnaire (ACQ) | The ACQ is a validated instrument containing 7 questions to assess asthma control which incorporates symptoms, beta-agonist use, and spirometry. Participants recall their experiences during the previous 7 days and respond to each question using a 7-point scale. The items are equally weighted and the ACQ score is the mean of the 7 items and therefore ranges between 0 (well controlled) and 6 (extremely poorly controlled). The ACQ completed on the day of exposure was the Baseline ACQ. Pooled standard deviations (SDs) and least square (LS) means were calculated based on an analysis of variates (ANOVA) model. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some ACQ follow-up information. | Posted | Least Squares Mean | Standard Deviation | units on a scale | Baseline through the Final Visit (Day 21) |
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| Secondary | LS Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Pooled SDs and LS means were calculated based on an ANOVA model. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some FEV1 follow-up information. | Posted | Least Squares Mean | Standard Deviation | liters | Baseline through the Final Visit (Day 21) |
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| Secondary | LS Mean Change From Baseline in Peak Expiratory Flow (PEF) in AM | PEF is a person's maximum speed of expiration as measured with a peak flow meter and was measured twice daily in the morning (AM) and evening (PM). Pooled SDs and LS means were calculated based on an ANOVA model. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some PEF follow-up information. | Posted | Least Squares Mean | Standard Deviation | L/min | Baseline through the Final Visit (Day 21) |
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| Secondary | LS Mean Change From Baseline in Peak Expiratory Flow (PEF) in PM | PEF is a person's maximum speed of expiration as measured with a peak flow meter and was measured twice daily in the morning (AM) and evening (PM). Pooled SDs and LS means were calculated based on an ANOVA model. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some PEF follow-up information. | Posted | Least Squares Mean | Standard Deviation | L/min | Baseline through the Final Visit (Day 21) |
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| Secondary | LS Mean Change From Baseline in Total Cold Symptom Score | Participants entered their cold symptoms into an e-diary twice daily beginning at the Screening Visit through completion of the study. The total cold symptom score was the sum of 6 scores for rhinorrhea, nasal congestion, cough, score throat, malaise, and myalgia. Each symptom is scored as follows: 0 = none-sign/symptom is not present, 1 = mild-sign/symptom noticeable but did not bother me or interfere with my normal daily activities/sleep, 2 = moderate- sign/symptom annoying and may have interfered with my normal daily activities/sleep, or 3 = severe-symptom very uncomfortable and interfered with most or all of my normal daily activities/sleep. The total score ranges from 0 to 18, with increasing scores reflecting more severe colds. Baseline values were defined as the average of the last seven assessments prior to randomization (before exposure to an index case). Pooled SDs and LS means were calculated based on an ANOVA model. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some cold symptom score follow-up information. | Posted | Least Squares Mean | Standard Deviation | units on a scale | Baseline through the Final Visit (Day 21) |
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| Secondary | LS Mean Change From Baseline in Total Asthma Symptom Score | Participants entered their asthma symptoms into an e-diary twice daily beginning at the Screening Visit through completion of the study. The total asthma symptom score was the sum of 3 scores for wheeze, cough, and dyspnea. Each symptom is scored as follows: 0 = none-sign/symptom is not present, 1 = mild-sign/symptom noticeable but did not bother me or interfere with my normal daily activities/sleep, 2 = moderate- sign/symptom annoying and may have interfered with my normal daily activities/sleep, or 3 = severe-symptom very uncomfortable and interfered with most or all of my normal daily activities/sleep. The total score ranges from 0 to 9, with increasing scores reflecting more severe asthma. Baseline values were defined as the average of the last seven assessments prior to randomization (before exposure to an index case). Pooled SDs and LS means were calculated based on an ANOVA model. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some asthma symptom score follow-up information. | Posted | Least Squares Mean | Standard Deviation | units on a scale | Baseline through the Final Visit (Day 21) |
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| Secondary | LS Mean Change From Baseline in Short-acting Beta-Agonist (SABA) Rescue Medication Usage | SABAs such as albuterol were permitted during the study as rescue medication and required a 6-hour washout prior to each visit. Participants entered their asthma medication use into an e-diary twice daily beginning at the Screening Visit through completion of the study. The Baseline for diary symptoms was the average of the last seven assessments prior to Randomization. Pooled SDs and LS means were calculated based on an ANOVA model. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some SABA follow-up information. | Posted | Least Squares Mean | Standard Deviation | number of puffs of SABA | Baseline through the Final Visit (Day 21) |
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| Secondary | LS Mean Change From Baseline in Asthma-Related Sleep Interference | Participants entered their asthma-related changes in sleep into an e-diary once daily (in the morning) beginning at the Screening Visit through completion of the study. Changes from Baseline in asthma-related sleep interference were determined using the following question: How did cold and asthma symptoms interfere with your sleep? The question was scored as follows: 0 = None, no interference with sleep at all, 1 = Mild, not annoying or troublesome, adequate amount of sleep, 2 = Moderate, interfered somewhat with sleep, woke up a few times, average sleep, 3 = Severe, substantially interfered with sleep, poor sleep. The Baseline for diary symptoms was the average of the last seven assessments prior to Randomization. Pooled SDs and LS means were calculated based on an ANOVA model. | Efficacy analyses were based on all randomized participants (intent-to-treat principle) with at least some sleep follow-up information. | Posted | Least Squares Mean | Standard Deviation | units on a scale | Baseline through the Final Visit (Day 21) |
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AE data is reported from the time of randomization to the end of the Follow-up Period (Day 21). The Screening Period and Pre-Exposure Periods are not included in this time frame.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pleconaril | Participants received Pleconaril nasal spray 4 sprays per nostril twice daily (BID), 24 mg/day for 1 week during the Treatment Period for a total of 14 doses. | 0 | 154 | 6 | 154 | ||
| EG001 | Placebo | Participants received placebo nasal spray 4 sprays per nostril BID for 1 week during the Treatment Period for a total of 14 doses. | 0 | 157 | 9 | 157 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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The investigator agrees not to publish or publicly present any interim results
of the study without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D003139 | Common Cold |
| D010850 | Picornaviridae Infections |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
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| ID | Term |
|---|---|
| C115201 | pleconaril |
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| Withdrawal by Subject |
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| Noncompliance with protocol |
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| Did not meet protocol eligibility |
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| Male |
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| OG001 | Placebo | Participants received placebo nasal spray 4 sprays per nostril BID for 1 week during the Treatment Period for a total of 14 doses. |
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Participants received placebo nasal spray 4 sprays per nostril BID for 1 week during the Treatment Period for a total of 14 doses.
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