- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00683449
Study Evaluating the Safety and Effects of MN-221 in Subjects Experiencing an Acute Exacerbation of Asthma
A Phase II, Randomized, Modified Single-Blind, Placebo-Controlled Dose Escalation Study to Evaluate the Safety and Efficacy of MN-221 When Administered Intravenously as an Adjunct to Standard Therapy to Adults With an Acute Exacerbation of Asthma
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
This is a randomized, modified single-blind, placebo-controlled dose escalation, multi-center Emergency Department (ED) study. Each subject will receive MN-221 or placebo administered through a continuous intravenous infusion in addition to the standardized care treatment for an acute exacerbation of asthma. The study is a modified single-blind design where the subject and the Investigator will be blinded.
Upon presentation to the ED for assessment and treatment for an acute exacerbation of asthma the subject should receive standardized care consistent with the National Asthma Education and Prevention Program (NAEPP) guidelines.
Once the subject has received the standardized initial treatment regimen and has been assessed for response to that treatment (signs and symptoms of acute asthma exacerbation), an informed consent to participate in the study will be obtained, study entry criteria will be reviewed, a 12-lead ECG will be performed, a dyspnea index scale assessment will be conducted, and spirometry will be performed. If the subject's FEV1 is ≤ 55% of predicted and the subject meets all other study entry criteria the subject will be randomized to receive either MN-221 or placebo. Throughout the screening process the subject will continue to receive the appropriate medical care consistent with the NAEPP guidelines for the treatment of acute exacerbations of asthma.
There will be up to three dose groups with generally twelve subjects in each group. Subjects enrolled in the study will receive an intravenous infusion of MN-221 study drug or placebo. Generally six subjects will be randomized to receive MN-221 and generally six subjects will be randomized to receive placebo in each dose group.
The initial dose group will be randomized to receive:
- 16 μg/min of MN-221 for 15 minutes (total dose of 240 μg) or placebo.
Subsequent dose groups will receive the following proposed doses:
- 30 μg/min for 15 minutes (total dose of 450 μg) or placebo, and
- 16 μg/min for 15 minutes followed by 8 μg/min for 105 minutes (total dose of 1,080 μg) or placebo.
During the study treatment period, the subject will continue to receive the following standard treatment and assessment until the subject's FEV1 reaches ≥ 70% of predicted:
- Assessment of subject's signs and symptoms;
- Complete a dyspnea index scale;
- Supplemental oxygen to maintain oxygen saturation as measured by pulse oximetry of ≥ 90%;
- Albuterol (2.5 mg) via nebulizer given hourly; NOTE: Albuterol (2.5 mg) via nebulizer may be given up to every 20 minutes if deemed to be indicated by the Investigator.
- Ipratropium (0.5 mg) via nebulizer may be given every hour if deemed to be indicated by the Investigator.
- Spirometry completed within 10 minutes of nebulizer treatments; followed by,
- Reassessment of signs and symptoms. If the subject does not improve to FEV1 ≥ 70% of predicted during the study treatment period, the subject may continue to receive further treatment including hospital admission at the discretion of the Investigator. The study will be approximately 6.5 hours in length (Hour -1.5 to Hour 5) while the subject remains in the ED. Safety, efficacy and PK parameters will be monitored throughout the treatment period. An initial 24-hour post-randomization follow-up visit will be completed to evaluate the subject's health status as well as for safety and PK parameters. A second follow-up contact will be completed by telephone seven days post-randomization for safety purposes and to evaluate the subject's health status.
A risk/benefit evaluation will be performed by the study's Safety Review Committee at each dose level. The occurrence of clinical signs, symptoms, laboratory abnormalities, ECG abnormalities suggesting toxicity, or results of efficacy analyses (FEV1, dyspnea index scale), may result in a decision to modify the proposed planned dose escalations, to repeat a dose level, or to not evaluate any additional dose(s) of MN-221.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
-
-
Arizona
-
Phoenix, Arizona, États-Unis, 85008
- Maricopa Medical Center; Dept. of Emergency Medicine
-
-
California
-
Los Angeles, California, États-Unis, 90033
- LAC + USC Medical Center
-
Sylmar, California, États-Unis, 91342
- Olive View - UCLA Medical Center
-
-
Michigan
-
Detroit, Michigan, États-Unis, 48208
- Henry Ford Health System
-
-
Missouri
-
St. Louis, Missouri, États-Unis, 63110
- Washington University School of Medicine; Div. of Emergency Medicine
-
-
New York
-
Brooklyn, New York, États-Unis, 11215
- New York Methodist Hospital
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New Hyde Park, New York, États-Unis, 11040
- Long Island Jewish Medical Center
-
-
Ohio
-
Cleveland, Ohio, États-Unis, 44109
- MetroHealth Medical Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, États-Unis, 19141
- Albert Einstein Medical Center
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Male or female;
- Have self-reported history of physician-diagnosed and treated asthma for ≥ 3 months;
- Have a diagnosis of an acute exacerbation of asthma upon presentation at the ED as defined by dyspnea and evidence of bronchospasm in an individual with a known history of asthma;
Upon presentation to the ED the treatment provided included:
- A brief history and physical examination that includes vital signs, auscultation, assessments of accessory respiratory muscle usage and the level of dyspnea the subject is experiencing;
- Supplemental oxygen given to maintain oxygen saturation as measured by pulse oximetry of ≥ 90%;
- Two doses of inhaled beta2-agonist (defined as albuterol 5 mg) via nebulizer (each dose given sequentially up to approximately every 20 minutes); simultaneously with
- Two doses of an inhaled anti-cholinergic agent (defined as ipratropium 0.5 mg) via nebulizer (each dose given sequentially up to approximately every20 minutes);
- One dose of corticosteroid of at least 60 mg given orally (prednisone) or intravenously (methylprednisolone); and
- Have a FEV1 ≤ 55% within 10 minutes of completing the treatment described in Inclusion Criterion #4;
- Have a negative urine pregnancy test if you are females of childbearing potential;
- Have ECG with no dysrhythmias (except sinus tachycardia);
- Have no clinical or electrocardiographic signs of ischemic heart disease as determined by the Investigator; and
- Have signed the informed consent obtained prior to starting any study procedures.
Exclusion criteria:
- Have a current or prior diagnosis or suspected diagnosis of COPD or other chronic lung disease other than asthma;
- Have presence of pneumonia;
- Have presence of significant other respiratory dysfunction such as pneumothorax, pneumomediastinum, or pulmonary edema;
- Have known or suspected vocal cord dysfunction syndrome;
- Have presence of aspirated foreign body (known or suspected);
- Have a history or any current clinical evidence suggesting cardiomyopathy or congestive heart failure;
- Have a history or presence of tachyarrhythmias, with the exception of sinus tachycardia;
- Have a heart rate ≥ maximum heart rate: (maximum predicted HR [220-age]-30); OR Heart rate ≥ 150 bpm;
- Have hypokalemia, defined as a potassium level ≤ 3.0 mg/dL according to the point-of-care device level obtained at Screening;
- Have significant cardiac, renal, hepatic, endocrine, metabolic, neurologic or other systemic disease. A significant disease will be defined as one which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study or the subject's ability to participate in the trial;
- Have a self-reported history of greater than 15 pack-yr smoking history;
- Have a fever ≥ 101.5º F;
- Have uncontrolled hypertension defined as a blood pressure ≥ 170/100 mm Hg;
- Have the need for immediate intubation as determined by the Investigator;
- Are a pregnant or lactating female;
- Have participated in another clinical study with an investigational drug within 30 days of randomization;
- Have a positive urine drug screen for cocaine, methamphetamine or PCP;
- Have a known allergy to MN-221 or any of the other components of the MN-221 drug product ;
- Have a known allergy to other beta agonists;
- Have had previous exposure to MN-221; or
- Have used of theophylline, beta blockers, diuretics, digoxin, MAO inhibitors, or tricyclic antidepressants within 2 weeks prior to randomization.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Seul
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: IV infusion of MN-221
MN-221 total dose of 240 mcg
|
IV infusion of MN-221 16 mcg/min for 15 min; total dose of 240 mcg
Autres noms:
i.v.
infusion of MN-221 30 mcg/min for 15 minutes (total dose of 450 mcg)
Autres noms:
i.v.
infusion of MN-221 16 mcg/min for 15 minutes followed by 8 mcg/min for 105 minutes (total dose = 1,080 mcg)
Autres noms:
|
Comparateur placebo: MN-221 PLACEBO
i.v.
infusion of MN-221 Placebo for 15 min
|
i.v.
infusion of placebo for 15 minutes
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Change of FEV1 (Forced Expiratory Volume in 1 Second) Expressed as Percent of Predicted After Two Doses of Albuterol (5 mg Each) and Ipratropium (0.5 mg Each) When Compared to FEV1 at Hour 2 After the Start of the Infusion of MN-221 or Placebo.
Délai: Baseline and Hour 2
|
The primary efficacy summary was change from Baseline in FEV1 (percent predicted), at Hour 2. Baseline was defined as FEV1 (percent predicted) after two doses of albuterol (5 mg each) and ipratropium (0.5 mg each) and FEV1 (percent predicted) FEV1 at Hour 2 was defined as the FEV1 (percent predicted) at 2 hours after the start of the infusion of MN-221 or placebo.
Change from Baseline in FEV1 (percent predicted), was summarized by treatment group at Hour 2.
|
Baseline and Hour 2
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
FEV1 (L) The Forced Expiratory Volume in One Second as Measured in Liters Per Second.
Délai: Baseline to Hour 2
|
FEV1 (L) was determined over time using a spirometer.
Measure the mean change in FEV1 (L) from Baseline.
|
Baseline to Hour 2
|
Hospital Admission Rate During Visit 1
Délai: Hour -1.5 through Hour 5
|
After a patient in the emergency department (ED) presents with an acute exacerbation of asthma, the hospital proceeds with SOC procedures for this condition.
Despite treatment in the ED, it is sometimes necessary to admit the patient into the hospital.
In the study described here, the rate of hospital admissions was recorded.
|
Hour -1.5 through Hour 5
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Michael Kalafer, MD, MediciNova
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- MN-221-CL-006
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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