Single Dose Pharmacokinetics of Intranasal Fluticasone Delivered by a Fixed Combination With Azelastine (MP29 02) in Comparison to Two Different Fluticasone Nasal Sprays

February 4, 2022 updated by: MEDA Pharma GmbH & Co. KG

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

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

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • NRW
      • Cologne, NRW, Germany, 51063
        • ClinPharmCologne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female healthy subjects of any Ethnic origin, age from 18 to 45 years.
  2. Body mass index (BMI) from 18.5 to 30.0 kg/m2.
  3. 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).
  4. 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).
  5. Written informed consent.
  6. Able to demonstrate correct nasal spray application technique at screening.

Exclusion Criteria:

  1. History of allergic reaction or sensitivity to fluticasone propionate, azelastine hydrochloride or one of the excipients (e.g. benzalkoniumchloride, phenyl-ethyl alcohol, microcrystalline cellulose).
  2. Any evidence of clinically relevant acute or chronic cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrine, metabolic, mental, neurological, or other disease at screening.
  3. Positive ß-HCG pregnancy test, or established pregnancy, breast-feeding or planned pregnancy during the study.

    Lack of suitability for the study:

  4. History of haemophilia or coagulation disease.
  5. Significant history of orthostatic hypotension, fainting or blackouts.
  6. Existence of any surgical or medical condition, which might significantly alter the absorption, distribution, metabolism, or excretion of study drug.
  7. 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.
  8. 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).
  9. Positive results in HIV, HCV and HBsAg tests.
  10. 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).
  11. 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.
  12. Regular therapy with corticosteroids (e.g. fluticasone propionate) or antihistamines (e.g. azelastine hydrochloride).
  13. 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).
  14. 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.
  15. History of any nasal surgery or known clinically relevant abnormalities, such as rhinitis medicamentosa, polyposis, septum deviation with clinical symptoms, or nasal structural abnormalities.
  16. 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.
  17. History of malignancy within the past five years.
  18. Blood donation within the last 2 months prior to the start of the study.
  19. 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.
  20. Current smoker or smoking during the last year.
  21. Exposure to an investigational medicinal product within the last 3 months.
  22. 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).
  23. Subject is vegetarian or reports other strict dietary habits which would preclude the subject's acceptance of standardized meals.

    Administrative reasons:

  24. Lack of ability or willingness to give informed consent.
  25. Lack of willingness to have personal study related data collected, archived or transmitted according to protocol.
  26. Lack of willingness or inability to co-operate adequately.
  27. Anticipated non-availability for study visits/procedures.
  28. Vulnerable subjects (such as persons kept in detention).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Experimental: Azelastine, Fluticasone
TEST = MP29-02 = Combination product Azelastine Hydrochloride and Fluticasone Propionate nasal spray (= US formulation as used in pivotal studies)
TEST = MP29-02 = Combination product Azelastine Hydrochloride and Fluticasone Propionate nasal spray (= US formulation as used in pivotal studies)
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)
REF = FLU mono Fluticasone Propionate nasal spray (= essentially combination product formulation without any AZE; US FLU mono formulation as used in pivotal studies)
Active Comparator: Fluticasone
COMP = Fluticasone Propionate Nasal Spray, Roxane Laboratories = FLU mono Fluticasone propionate nasal spray (= US marketed product)
COMP = Fluticasone Propionate Nasal Spray, Roxane Laboratories = FLU mono Fluticasone propionate nasal spray (= US marketed product)

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
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)
up to 24 h post application
Effects of AZE on other pharmacokinetic parameters
Time Frame: up to 24 h post application
Effects of AZE on other pharmacokinetic parameters of FLU (AUC0 tlast, CL/f, Cmax, tmax, t½)
up to 24 h post application
Adverse Events
Time Frame: At and between treatment periods
Adverse Events
At and between treatment periods

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

October 1, 2010

Study Completion (Actual)

October 1, 2010

Study Registration Dates

First Submitted

September 2, 2010

First Submitted That Met QC Criteria

September 2, 2010

First Posted (Estimate)

September 3, 2010

Study Record Updates

Last Update Posted (Actual)

February 7, 2022

Last Update Submitted That Met QC Criteria

February 4, 2022

Last Verified

April 1, 2016

More Information

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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