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

This study has been completed.
Sponsor:
Collaborators:
ClinPharmCologne
ClinResearch GmbH, Cologne
Prolytic GmbH
pharm-analyt GmbH
Information provided by:
MEDA Pharma GmbH & Co. KG
ClinicalTrials.gov Identifier:
NCT01194622
First received: September 2, 2010
Last updated: December 7, 2010
Last verified: December 2010
  Purpose

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.


Condition Intervention Phase
Allergic Rhinitis
Drug: Azelastine, Fluticasone
Drug: Fluticasone mono
Drug: Fluticasone
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by MEDA Pharma GmbH & Co. KG:

Primary Outcome Measures:
  • Effect of azelastine hydrochloride on the relative bioavailability of fluticasone [ Time Frame: up to 24 h post application ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Relative bioavailability [ Time Frame: up to 24 h post application ] [ Designated as safety issue: Yes ]
    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)

  • Effects of AZE on other pharmacokinetic parameters [ Time Frame: up to 24 h post application ] [ Designated as safety issue: Yes ]
    Effects of AZE on other pharmacokinetic parameters of FLU (AUC0 tlast, CL/f, Cmax, tmax, t½)

  • Adverse Events [ Time Frame: At and between treatment periods ] [ Designated as safety issue: Yes ]
    Adverse Events


Enrollment: 30
Study Start Date: August 2010
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azelastine, Fluticasone
TEST = MP29-02 = Combination product Azelastine Hydrochloride and Fluticasone Propionate nasal spray (= US formulation as used in pivotal studies)
Drug: Azelastine, Fluticasone
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)
Drug: 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)
Active Comparator: Fluticasone
COMP = Fluticasone Propionate Nasal Spray, Roxane Laboratories = FLU mono Fluticasone propionate nasal spray (= US marketed product)
Drug: Fluticasone
COMP = Fluticasone Propionate Nasal Spray, Roxane Laboratories = FLU mono Fluticasone propionate nasal spray (= US marketed product)

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).

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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).
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194622

Locations
Germany
ClinPharmCologne
Cologne, NRW, Germany, 51063
Sponsors and Collaborators
MEDA Pharma GmbH & Co. KG
ClinPharmCologne
ClinResearch GmbH, Cologne
Prolytic GmbH
pharm-analyt GmbH
  More Information

No publications provided

Responsible Party: MEDA Pharma GmbH & Co. KG, Clinical Development
ClinicalTrials.gov Identifier: NCT01194622     History of Changes
Other Study ID Numbers: X-03065-3282, 2010-019557-18
Study First Received: September 2, 2010
Last Updated: December 7, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Rhinitis
Rhinitis, Allergic, Perennial
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Azelastine
Fluticasone
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Lipoxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Allergic Agents
Histamine H1 Antagonists, Non-Sedating
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on August 01, 2014