- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01194622
Single Dose Pharmacokinetics of Intranasal Fluticasone Delivered by a Fixed Combination With Azelastine (MP29 02) in Comparison to Two Different Fluticasone Nasal Sprays
Single Dose Pharmacokinetics of Intranasal Fluticasone Delivered by a Fixed Combination With Azelastine (MP29 02) in Comparison to Two Different Fluticasone Nasal Sprays Single-centre, Randomised, Open-label, Three-period, Six-sequence Cross-over Trial (William's Design)
The primary objective is to assess the effect of azelastine hydrochloride (AZE) on the relative bioavailability (AUC0-∞) of fluticasone propionate (FLU) when administered as fixed AZE-FLU combination product (TEST) compared to a similar formulation without containing AZE (i.e. FLU alone in the MP29-02 vehicle; REF).
The secondary objectives are to compare the relative bioavailability (AUC0-∞) of FLU when administered either as fixed AZE-FLU combination product (TEST) or as marketed FLU product, Fluticasone Propionate Nasal Spray, Roxane Laboratories (COMP); To compare the effects of AZE on other pharmacokinetic parameters of FLU (AUC0 tlast, CL/f, Cmax, tmax, t½); To assess adverse events.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study will enrol healthy subjects. It is considered that study results are more discriminative in healthy subjects than in rhinitis patients as there are no interferences by varying rhinitis symptoms and respective differences in the status of the nasal mucosa regarding the 3 study periods.
The time schedule for serum sampling (pre-dose and 8, 15, 30, 45 min, 1, 1¼, 1½, 2, 2½, 3, 4, 6, 8, 12, and 24 h p.a., time refer to the end of the second spray into the second nostril of each administration) is derived from previous bioavailability studies assuming a mean tmax of 1 h p.a. [P5] and a mean t1/2 of 3 h [L9]. Sampling times are expected to cover an AUC0-tlast above 80% of the total AUC of fluticasone propionate (bioanalytical detection method with a LLOQ of 0.5 pg/mL).
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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NRW
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Cologne, NRW, Germany, 51063
- ClinPharmCologne
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female healthy subjects of any Ethnic origin, age from 18 to 45 years.
- Body mass index (BMI) from 18.5 to 30.0 kg/m2.
- Use of adequate double contraception by female with childbearing potential (i.e. women of child bearing potential using a highly effective method of birth control defined as those which result in a low failure rate (i.e. <1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs) or surgically sterile (documented complete hysterectomy or bi-tubal ligations; partial hysterectomy is not sufficient or vasectomised partner). It must be ensured that the male partner uses a condom during intercourse (if not surgically sterilized).
- Use of adequate double contraception by male, who is a sexually active man and has not been surgically sterilized, must consent that he uses a condom during intercourse and ensures that his female partner practices adequate contraception (a highly effective method of birth control defined as those which result in a low failure rate (i.e. <1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs) or surgically sterile (documented complete hysterectomy or bi-tubal ligations; partial hysterectomy is not sufficient).
- Written informed consent.
- Able to demonstrate correct nasal spray application technique at screening.
Exclusion Criteria:
- History of allergic reaction or sensitivity to fluticasone propionate, azelastine hydrochloride or one of the excipients (e.g. benzalkoniumchloride, phenyl-ethyl alcohol, microcrystalline cellulose).
- Any evidence of clinically relevant acute or chronic cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrine, metabolic, mental, neurological, or other disease at screening.
Positive ß-HCG pregnancy test, or established pregnancy, breast-feeding or planned pregnancy during the study.
Lack of suitability for the study:
- History of haemophilia or coagulation disease.
- Significant history of orthostatic hypotension, fainting or blackouts.
- Existence of any surgical or medical condition, which might significantly alter the absorption, distribution, metabolism, or excretion of study drug.
- Chronic or clinically relevant acute infections (e.g. of the respiratory tract including sinusitis and rhinitis), acute rhinorrhoea or febrile disease the week before randomisation.
- Clinical chemical, haematological or any other laboratory parameters clinically relevant outside the reference range (e.g. elevated liver enzymes, renal laboratory parameters, and coagulation abnormalities such as abnormalities of platelet count, prothrombin time, or activated partial thromboplastin time).
- Positive results in HIV, HCV and HBsAg tests.
- ECG abnormalities of clinical relevance, in particular abnormal prolongations of QT/QTc- or PQ-interval (i.e. QTc according to Fridericia ≥ 450 ms, PQ ≥ 220 ms).
- Resting heart rate in the awake subject below 45 BPM or above 90 BPM, systolic blood pressure below 100 mmHg or above 145 mmHg, diastolic blood pressure above 95 mmHg.
- Regular therapy with corticosteroids (e.g. fluticasone propionate) or antihistamines (e.g. azelastine hydrochloride).
- Any concurrent medication or any medication within 2 weeks preceding the start of the study (single intake/use of drugs may be accepted, if judged by the investigator to have no clinical relevance and no influence on study outcome).
- Exposure to any cytochrome P450 3A4 inhibiting or inducing drug (e.g. ritonavir, ketoconazole, itraconazole, erythromycin, rifampicin, St. John's wort (Hypericum perforatum) etc.) diets (charcoal grilled meat, brussels sprouts, broccoli) or beverages (e.g. grapefruit juice) within 14 days prior to study enrolment, or anticipated consumption of such products during that period or at any time throughout the study.
- History of any nasal surgery or known clinically relevant abnormalities, such as rhinitis medicamentosa, polyposis, septum deviation with clinical symptoms, or nasal structural abnormalities.
- Known perennial airway allergies or vasomotor rhinitis. Known seasonal airway allergies which are clinically relevant acute within the last six weeks prior to the start of the study or might become acute during the study period.
- History of malignancy within the past five years.
- Blood donation within the last 2 months prior to the start of the study.
- Present or history of drug or alcohol abuse within the last three years. Regular daily consumption of more than half a litre of usual beer or 0.25 L of wine per day or the equivalent quantity of approximately 30 g of alcohol in another form.
- Current smoker or smoking during the last year.
- Exposure to an investigational medicinal product within the last 3 months.
- Subject reports a regular xanthine consumption of > 5 cups of coffee or black tea per day (or equivalent xanthine consumption of ≥ 500 mg xanthine per day using other products).
Subject is vegetarian or reports other strict dietary habits which would preclude the subject's acceptance of standardized meals.
Administrative reasons:
- Lack of ability or willingness to give informed consent.
- Lack of willingness to have personal study related data collected, archived or transmitted according to protocol.
- Lack of willingness or inability to co-operate adequately.
- Anticipated non-availability for study visits/procedures.
- Vulnerable subjects (such as persons kept in detention).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Azelastine, Fluticasone
TEST = MP29-02 = Combination product Azelastine Hydrochloride and Fluticasone Propionate nasal spray (= US formulation as used in pivotal studies)
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TEST = MP29-02 = Combination product Azelastine Hydrochloride and Fluticasone Propionate nasal spray (= US formulation as used in pivotal studies)
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Active Comparator: Fluticasone mono
REF = FLU mono Fluticasone Propionate nasal spray (= essentially combination product formulation without any AZE; US FLU mono formulation as used in pivotal studies)
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REF = FLU mono Fluticasone Propionate nasal spray (= essentially combination product formulation without any AZE; US FLU mono formulation as used in pivotal studies)
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Active Comparator: Fluticasone
COMP = Fluticasone Propionate Nasal Spray, Roxane Laboratories = FLU mono Fluticasone propionate nasal spray (= US marketed product)
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COMP = Fluticasone Propionate Nasal Spray, Roxane Laboratories = FLU mono Fluticasone propionate nasal spray (= US marketed product)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of azelastine hydrochloride on the relative bioavailability of fluticasone
Time Frame: up to 24 h post application
|
Effect of azelastine hydrochloride (AZE) on the relative bioavailability (AUC0-∞) of fluticasone propionate (FLU) when administered as fixed AZE-FLU combination product (TEST) compared to a similar formulation without containing AZE (i.e.
FLU alone in the MP29-02 vehicle; REF).
|
up to 24 h post application
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relative bioavailability
Time Frame: up to 24 h post application
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Relative bioavailability (AUC0-∞) of FLU when administered either as fixed AZE-FLU combination product (TEST) or as marketed FLU product, Fluticasone Propionate Nasal Spray, Roxane Laboratories (COMP)
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up to 24 h post application
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Effects of AZE on other pharmacokinetic parameters
Time Frame: up to 24 h post application
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Effects of AZE on other pharmacokinetic parameters of FLU (AUC0 tlast, CL/f, Cmax, tmax, t½)
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up to 24 h post application
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Adverse Events
Time Frame: At and between treatment periods
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Adverse Events
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At and between treatment periods
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Immune System Diseases
- Hypersensitivity, Immediate
- Otorhinolaryngologic Diseases
- Respiratory Hypersensitivity
- Hypersensitivity
- Nose Diseases
- Rhinitis
- Rhinitis, Allergic
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Dermatologic Agents
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Anti-Allergic Agents
- Histamine H1 Antagonists
- Histamine Antagonists
- Histamine Agents
- Histamine H1 Antagonists, Non-Sedating
- Lipoxygenase Inhibitors
- Fluticasone
- Xhance
- Azelastine
Other Study ID Numbers
- X-03065-3282
- 2010-019557-18 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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