Eficacia y seguridad de OPN-375 en adolescentes con pólipos nasales bilaterales
Estudio multicéntrico de grupos paralelos controlado con placebo, doble ciego, aleatorizado, de 16 semanas de duración que evalúa la eficacia y la seguridad de OPN-375 186 μg dos veces al día en adolescentes con pólipos nasales bilaterales seguido de una fase de tratamiento abierto de 12 semanas
This is a 16-Week Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of OPN-375 186 μg Twice a Day (BID) in Adolescents with Bilateral Nasal Polyps followed by a 12-Week Open-Label Treatment Phase. The total planned number of subjects is approximately 72 adolescents (12-17 years of age) who will be randomly assigned to receive 1 of 2 study treatments using a 2:1 ratio (OPN-375 186 μg: Placebo). For the PK sub-study, up to 14 subjects will be enrolled to obtain 10 completers.
Descripción general del estudio
Descripción detallada
The primary objective of this study is to evaluate the efficacy of intranasal administration of OPN-375 186 μg Twice a Day (BID) versus placebo in adolescents with bilateral nasal polyposis and nasal congestion by analyzing the reduction of nasal congestion/obstruction symptoms at the end of Week 4 measured by the 7-day average instantaneous morning diary symptom scores and the reduction in total polyp grade at Week 16 as determined by a nasal polyp grading scale score measured using a 0 to 6 point severity grading scale.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Buenos Aires, Argentina, C1411ABE
- Fundacion CIDEA
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Buenos Aires, Argentina, C1425BEN
- InAER - Investigaciones en Alergia y Enfermedades Respiratorias
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Buenos Aires, Argentina, C1180AAX
- Sanatorio Guemes
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Corrientes, Argentina, W3400AVV
- Instituto de Asma Alergia y Enfermedades Respiratoria (IAAER)
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Mendoza, Argentina, M5500CCG
- Centro Medico INSARES
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Córdoba Province
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Río Cuarto, Córdoba Province, Argentina, X5008AEV
- Instituto Medico Rio Cuarto
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Santa Fe Province
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Rosario, Santa Fe Province, Argentina, S2000DEJ
- Instituto Medico de la Fundacion de Estudios Clinicos - Consultorios Integrados Rosario
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Rosario, Santa Fe Province, Argentina, S200DBS
- Centro de Investigaciones Clinicas - Instituto de la Salud Rosario
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Tucumán Province
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San Miguel de Tucumán, Tucumán Province, Argentina, T4000IHE
- Clinica Mayo, UMCB
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Arizona
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Gilbert, Arizona, Estados Unidos, 85234
- San Tan Allergy & Asthma
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California
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Bakersfield, California, Estados Unidos, 93301
- Kern Research
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Fresno, California, Estados Unidos, 93720
- Central California Clinical Research
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Los Angeles, California, Estados Unidos, 90027
- Children's Hospital of Los Angeles
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Los Angeles, California, Estados Unidos, 90006
- Sensa Health
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Orange, California, Estados Unidos, 92868
- Children's Hospital of Orange County
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Redwood City, California, Estados Unidos, 94063
- Allergy and Asthma Consultants
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Roseville, California, Estados Unidos, 95661
- Sacramento ENT
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San Diego, California, Estados Unidos, 92123
- Rady Children's Hospital San Diego
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- Children's Hospital Colorado
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Children's Healthcare of Atlanta
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Illinois
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Chicago, Illinois, Estados Unidos, 60657
- Chicago ENT
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Kentucky
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Louisville, Kentucky, Estados Unidos, 40205
- Kentuckiana ENT
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New York
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Rochester, New York, Estados Unidos, 14642
- University of Rochester
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North Carolina
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Charlotte, North Carolina, Estados Unidos, 28204
- Allergy Asthma & Immunology Research Institute
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73120
- Allergy, Asthma & Clinical Research Center
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Tulsa, Oklahoma, Estados Unidos, 74136
- Vital Prospects Clinical Research Institute, P.C.
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South Carolina
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Orangeburg, South Carolina, Estados Unidos, 29118
- Carolina ENT
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Texas
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San Antonio, Texas, Estados Unidos, 78229
- STAAMP Research
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Utah
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Salt Lake City, Utah, Estados Unidos, 84132
- University of Utah
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Virginia
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Norfolk, Virginia, Estados Unidos, 23507
- Eastern Virginia Medical School - Otolaryngology
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Washington
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Spokane Valley, Washington, Estados Unidos, 99216
- Spokane ENT
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Male or female subjects aged 12 to 17 years, inclusive, at time of Visit 1 (Screening).
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Female subjects, if sexually active, must,
- be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], or male partner sterilization) before entry and throughout the study, or
- be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or
- be abstinent.
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All female subjects not documented to be infertile (e.g., infertility due to congenital abnormality or surgical sterilization) must have a negative serum or urine beta-human chorionic gonadotropin (hCG) at Visit 1 (Screening) and a negative urine pregnancy test at the Visit 2 (Day 1/Randomization/Baseline).
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Must have bilateral nasal polyposis with a grade of 1 to 3 in each of the nasal cavities as determined by a nasal polyp grading scale score measured by nasoendoscopy at Visit 1 (Screening).
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Must report at least mild symptoms of nasal congestion/obstruction as demonstrated by an average morning nasal congestion/obstruction score of at least 1.0 over a 7 day period during the single-blind run-in period. (Subjects not meeting this inclusion criterion may be re-screened once after at least 4 weeks.)
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Subjects with comorbid asthma must be stable, defined as no exacerbations (e.g., no emergency room visits, hospitalization, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Subjects who received inhaled corticosteroids are required to be on no more than a moderate dosage regimen as defined by 2015 Global Initiative for Asthma Guidelines (GINA) for 1 month before Visit 1 (Screening) and to be expected to remain on it throughout the study (GINA 2015). Subjects receiving inhaled fluticasone alone or in combination may not participate in the PK sub-study.
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Must be able to cease treatment with intranasal medications including, but not limited to, intranasal oxymetazoline or any other decongestants, intranasal antihistamines, intranasal steroids, intranasal sodium cromolyn, nasal atropine, nasal ipratropium bromide, inhaled corticosteroids (except permitted doses listed above for asthma) at Visit 1 (Screening). [Note: intranasal antibiotics and saline are permissible]
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If taking oral antihistamines, must be on a stable regimen for at least 2 weeks prior to Visit 1 (Screening), and agree to not change the dose of these medications until after Visit 3 (Week 4) of the study.
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Subjects (with assistance from parent or legal guardian if needed) must demonstrate the ability to complete the daily diary during the run-in period to be eligible for randomization.
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Must demonstrate correct use of the demo EDS.
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Must be capable, in the opinion of the investigator, of providing assent and the appropriate parent(s) or guardian must provide an informed consent to participate in the study.
Exclusion Criteria:
- Pregnancy or lactation
- Has a history of cystic fibrosis
- Have used XHANCE (fluticasone propionate) nasal spray within the past 2 months
- Inability to achieve bilateral nasal airflow for any reason, including nasal septum deviation
- Inability to examine both nasal cavities for any reason, including severe nasal septum deviation
- Have known history of nasal septum erosion, ulceration or perforation, or evidence of such lesion on Visit 1 (Screening) nasal examination/nasoendoscopy
- Other significant nasal pathology or abnormal anatomy
- Has had any episode of epistaxis with frank bleeding in the 3 months before Visit 1 (Screening)
- History of more than 5 sinus or nasal surgeries for either nasal polyps or nasal/sinus inflammation (lifetime)
- Have had any surgery on the nasal septum
- History of sinus or nasal surgery within 6 months before Visit 1 (Screening)
- History of any surgical procedure that prevents the ability to accurately diagnose or grade polyps
- Current, ongoing rhinitis medicamentosa (rebound rhinitis)
- Have significant oral structural abnormalities (e.g., a cleft palate)
- History of Churg-Strauss syndrome or dyskinetic ciliary syndromes
- Purulent nasal infection (recent fever or symptoms of lethargy), acute sinusitis, or upper respiratory tract infection within 2 weeks before Visit 1 (Screening). Potential subjects presenting with one of these infections may be rescreened after 4 weeks.
- Have an allergy, hypersensitivity, or contraindication to corticosteroids or steroids
- Have a hypersensitivity to any excipients in the study drug
- Exposure to any glucocorticoid treatment with potential for systemic effects (e.g., oral or parenteral steroids, high dose topical steroids) within 1 month before Visit 1 (Screening); except as noted in inclusion criteria for subjects with comorbid asthma
- Have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1
- Have nasal or oral candidiasis
- Have taken a potent CYP3A4-inhibitor within 14 days before Visit 1 (Screening)
- Any serious or unstable concurrent disease, psychiatric disorder, or any significant concomitant medical condition that, in the opinion of the investigator could confound the results of the study or could interfere with the subject's participation or compliance in the study, or pose a specific risk to the subject due to study participation
- History or current diagnosis of any form of glaucoma or ocular hypertension (i.e., >21 mm Hg)
- History of intraocular pressure elevation on any form of steroid therapy
- Current diagnosis of the presence (in either eye) of a cataract of Grade 1 or greater as defined on the Eye Examination Worksheet OR, less than a Grade 1 cataract with associated visual impairment
- A recent (within 1 year of Visit 1 [Screening]) history of drug or alcohol abuse or dependence
- Positive urine drug screen at screening visit for stimulants, opioids, or cocaine
- Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
- Parents, guardian or caregivers of the subject who are employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: OPN-375 186 μg BID
Double-Blind Treatment Phase: OPN-375 186 μg BID x 16 weeks Open-Label Extension Phase: OPN-375 186 μg BID x 12 weeks |
OPN-375, BID |
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Comparador de placebos: Placebo
Double-Blind Treatment Phase: Matching Placebo BID x 16 weeks |
OPN-375, BID |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in nasal congestion/obstruction symptoms (mild, moderate, severe) at the end of Week 4
Periodo de tiempo: 4 Weeks
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Change in nasal congestion/obstruction symptoms at the end of Week 4 measured by the 7-day average instantaneous morning (AM) diary symptom scores (ADS7-IA). The nasal symptom scale is what is used to score the nasal congestion/obstruction score, which is recorded in the diary. Nasal symptom scale is graded on a scale of 0=no symptom, 1=mild symptom, 2=moderate symptom, 3=severe symptom. |
4 Weeks
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Mean change from baseline at Week 16 in total polyp grade
Periodo de tiempo: 16 Weeks
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Change in total polyp grade (sum of scores from both nasal cavities) at Week 16 as determined by a nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril |
16 Weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in bilateral polyp grade over time
Periodo de tiempo: 16 Weeks
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nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril |
16 Weeks
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Percentage of subjects with a ≥1 point improvement in polyp grade
Periodo de tiempo: 16 Weeks
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nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril |
16 Weeks
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Percentage of subject with a grade of 0 on at least one side of the nose
Periodo de tiempo: 16 Weeks
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nasal polyp grading scale score measured using a 0 to 6 point severity grading scale, with 0 (no polyps) to 3 (severe polyps) points per nostril |
16 Weeks
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Change in diary symptom scores for the symptoms of nasal congestion/obstruction, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Periodo de tiempo: 16 Weeks
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The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom) |
16 Weeks
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Change in diary symptom scores for the symptoms of rhinorrhea, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Periodo de tiempo: 16 Weeks
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The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom) |
16 Weeks
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Change in diary symptom scores for the symptoms of facial pain or pressure, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Periodo de tiempo: 16 Weeks
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The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom) |
16 Weeks
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Change in diary symptom scores for the sense of smell, measured as instantaneous and reflective scores for the morning and the afternoon (AM and PM scores)
Periodo de tiempo: 16 Weeks
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Sense of smell will be scored on a scale from 0 (normal) to 3 (absent, no sense of smell) |
16 Weeks
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The proportions of subjects who have reductions in the AM and PM, instantaneous and reflective, average nasal congestion/obstruction symptom scores by 0.5 or more points from baseline to the end of the double-blind treatment phase
Periodo de tiempo: 16 Weeks
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The Nasal Symptom Scale is graded on a scale of 0 (no symptom) to 3 (Severe symptom) |
16 Weeks
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Subjects will assess their global impression of change since starting the study drug using the PGIC scale
Periodo de tiempo: 16 Weeks
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Subject global impression of change will be assessed using a subject-completed PGIC scale, with a single question rated from 1=very much improved to 7=very much worse |
16 Weeks
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Subjects will assess their change in quality of life since starting the study drug using the quality of life questionnaire (SN-5).
Periodo de tiempo: 16 Weeks
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Quality of life assessment using the SN-5 Questionnaire, a subject/parent-completed questionnaire that consists of 5 specific symptoms-related questions (answered on a 7-point Likert scale on the frequency of symptoms, 1=none of the time, 7=all of the time), and 1 general overall quality of life question (answered on a visual analog scale from 0 to 10, worst to best). |
16 Weeks
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Proportion of subjects eligible for surgical intervention (independent of actual surgery performed)
Periodo de tiempo: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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The assessment criteria are as follows:
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Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Evaluación de la seguridad a partir de la recopilación de información para el uso de medicamentos concomitantes
Periodo de tiempo: 16 semanas
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16 semanas
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Assessment of safety from physical examination-measuring weight
Periodo de tiempo: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety from physical examination-weight measured in kg or lb |
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety from physical examination-measuring height
Periodo de tiempo: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety from physical examination-height measured in cm or in |
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety by recording the severity of AEs
Periodo de tiempo: 16 Weeks
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Assessment of safety by measuring severity of AEs using scale with 1=mild, 2=moderate, 3=severe |
16 Weeks
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Assessment of safety by nasal examination
Periodo de tiempo: 16 Weeks
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Assessed in nasal examination worksheet which includes recording the presence of any epistaxis, septal erosion/perforation, ulceration/erosion of area other than septum. If present, the nostril location is also recorded, along with severity, and if there is any relation to an injury or trauma |
16 Weeks
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Assessment of safety by ocular examination-visual acuity
Periodo de tiempo: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety by performing visual acuity test assessment using eye chart. Separate recording for each eye in the form of a fraction, 20/... |
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety by ocular examination-Intraocular Pressure
Periodo de tiempo: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety by averaging intraocular pressure measurement of 2 or 3 measurements to determine if it is >21mmHg |
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety by ocular examination-Cataract Evaluation
Periodo de tiempo: Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Cataracts should be again assessed present or absent, If cataract is diagnosed, cataract type per localization should be specified and cataract should be graded 1=mild, 2=moderate, 3=pronounced, 4=severe |
Visit 1 (Screening) and Visit 6 (Week 16/ End of Double-Blind/Early Termination)
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Assessment of safety measuring vital signs (blood pressure)
Periodo de tiempo: 16 Weeks
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Includes systolic and diastolic blood pressure measurements in millimeter of mercury (mmHg) |
16 Weeks
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Assessment of safety measuring vital signs (pulse)
Periodo de tiempo: 16 Weeks
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measure pulse in beats per minute (bpm) |
16 Weeks
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Assessment of pharmacokinetics - AUC(0-t) (pg*hr/mL)
Periodo de tiempo: 8 hours, 1 to 2 weeks before randomization
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PK Laboratory to determine the concentrations of fluticasone propionate [AUC(0-t) (pg*hr/mL) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose. |
8 hours, 1 to 2 weeks before randomization
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Assessment of pharmacokinetics - AUC(0-∞) (pg*hr/mL)
Periodo de tiempo: 8 hours, 1 to 2 weeks before randomization
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PK Laboratory to determine the concentrations of fluticasone propionate [AUC(0-∞) (pg*hr/mL) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose. |
8 hours, 1 to 2 weeks before randomization
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Assessment of pharmacokinetics - AUCex (%)
Periodo de tiempo: 8 hours, 1 to 2 weeks before randomization
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PK Laboratory to determine the concentrations of fluticasone propionate [AUCex (%) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose. |
8 hours, 1 to 2 weeks before randomization
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Assessment of pharmacokinetics - Cmax (pg/mL)
Periodo de tiempo: 8 hours, 1 to 2 weeks before randomization
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PK Laboratory to determine the concentrations of fluticasone propionate [Cmax (pg/mL) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose. |
8 hours, 1 to 2 weeks before randomization
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Assessment of pharmacokinetics - tmax (h)
Periodo de tiempo: 8 hours, 1 to 2 weeks before randomization
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PK Laboratory to determine the concentrations of fluticasone propionate [tmax (h) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose. |
8 hours, 1 to 2 weeks before randomization
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Assessment of pharmacokinetics - t1/2 (h)
Periodo de tiempo: 8 hours, 1 to 2 weeks before randomization
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PK Laboratory to determine the concentrations of fluticasone propionate [t1/2 (h) measurement] in human plasma using high performance liquid chromatography (HPLC) with mass spectrometric detection. Approximately 5 mL of blood is collected from each subject at 10 different timepoints over an 8-hour period, for a total of 50 mL. The timepoints are: Pre-dose; 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 3 hours, 6 hours and 8 hours post-dose. |
8 hours, 1 to 2 weeks before randomization
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Amy Manley, Paratek Pharma
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Otros números de identificación del estudio
- OPN-FLU-NP-3103
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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