Effects of Pleconaril Nasal Spray on Common Cold Symptoms and Asthma Exacerbations Following Rhinovirus Exposure (Study P04295)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00394914
First received: October 31, 2006
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Asthma
Common Cold
Picornavirus Infection
Rhinovirus
Drug: Pleconaril
Drug: Placebo to Pleconaril
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Placebo-Controlled Study of the Effects of Pleconaril Nasal Spray on Common Cold Symptoms and Asthma Exacerbations Following Rhinovirus Exposure

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With Rhinovirus PCR-Positive Colds [ Time Frame: From time of exposure to index case to end of Follow-up Period (21 days) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Asthma Exacerbations Together With Rhinovirus-Positive PCR [ Time Frame: From time of exposure to index case to end of Follow-up Period (21 days) ] [ Designated as safety issue: No ]

    Asthma exacerbation was defined as a participant having one of the following:

    1. 0.5 point or more increase in the Asthma Control Questionnaire (ACQ) from Baseline at Day 7. 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.
    2. Any change to asthma treatment as prescribed by a physician, unscheduled contact (either office visit or phone contact where medication was changed for asthma symptoms), emergency room visit, or hospitalization.

    PCR+ was defined as positive or equivocal outcome of the picornavirus test any time after randomization.



Secondary Outcome Measures:
  • LS Mean Change From Baseline in the Asthma Control Questionnaire (ACQ) [ Time Frame: Baseline through the Final Visit (Day 21) ] [ Designated as safety issue: No ]
    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.

  • LS Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline through the Final Visit (Day 21) ] [ Designated as safety issue: No ]
    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.

  • LS Mean Change From Baseline in Peak Expiratory Flow (PEF) in AM [ Time Frame: Baseline through the Final Visit (Day 21) ] [ Designated as safety issue: No ]
    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.

  • LS Mean Change From Baseline in Peak Expiratory Flow (PEF) in PM [ Time Frame: Baseline through the Final Visit (Day 21) ] [ Designated as safety issue: No ]
    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.

  • LS Mean Change From Baseline in Total Cold Symptom Score [ Time Frame: Baseline through the Final Visit (Day 21) ] [ Designated as safety issue: No ]
    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.

  • LS Mean Change From Baseline in Total Asthma Symptom Score [ Time Frame: Baseline through the Final Visit (Day 21) ] [ Designated as safety issue: No ]
    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.

  • LS Mean Change From Baseline in Short-acting Beta-Agonist (SABA) Rescue Medication Usage [ Time Frame: Baseline through the Final Visit (Day 21) ] [ Designated as safety issue: No ]
    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.

  • LS Mean Change From Baseline in Asthma-Related Sleep Interference [ Time Frame: Baseline through the Final Visit (Day 21) ] [ Designated as safety issue: No ]
    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.


Enrollment: 311
Study Start Date: August 2006
Study Completion Date: April 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pleconaril
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.
Drug: Pleconaril
Pleconaril nasal suspension is supplied in a bottle containing 120 actuations. Each actuation contains 1.5 mg of pleconaril.
Other Name: SCH 900819
Placebo Comparator: Placebo
Participants will receive placebo nasal spray 4 sprays per nostril BID for 1 week during the Treatment Period for a total of 14 doses.
Drug: Placebo to Pleconaril
Placebo nasal suspension

  Eligibility

Ages Eligible for Study:   6 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

    • For participants 6 to 17 years of age, exacerbations for the purpose of the inclusion criteria, will be defined as:
    • An increase of four or more puffs of a short-acting beta-agonist (SABA) per day for at least 3 consecutive days, or
    • An increase of two or more nebulizations of a SABA per day for at least 3 consecutive days, or
    • Documentation of morning (AM) peak flow drops >20% per day for at least 2 consecutive days, or
    • Documentation of AM peak flow drops of ≥50% for at least 1 day.
  • 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:

  • Had an upper or lower respiratory illness or exhibits signs and/or symptoms of a respiratory illness in the 4 weeks prior to the Screening Visit.
  • Received any treatment more recently than the indicated washout period prior to Screening or who must continue to receive treatment that is prohibited.
  • Smoker or ex-smoker and has smoked within the previous 5 years of Screening or has had a cumulative smoking history >10 pack years.
  • Allergy/sensitivity to the study drug or its excipients.
  • Female who is breast-feeding, pregnant, or intends to become pregnant.
  • Used any investigational drugs within 30 days of Screening.
  • Participating in any other clinical study.
  • Part of the staff personnel directly involved with this study.
  • Family member of the investigational study staff.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00394914     History of Changes
Other Study ID Numbers: P04295, Doc ID: 3303796
Study First Received: October 31, 2006
Results First Received: August 27, 2013
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Common Cold
Asthma
Picornaviridae Infections
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Pleconaril
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014