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

NCT01194622 | Completed Phase 1

• 2 other identifiers: X-03065-32822010-019557-18
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Allergic Rhinitis

Outcome Measures

Primary Outcomes (1)

• Effect of azelastine hydrochloride on the relative bioavailability of fluticasone

  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 Outcomes (3)

• Relative bioavailability

  up to 24 h post application

• Effects of AZE on other pharmacokinetic parameters

  up to 24 h post application

• Adverse Events

  At and between treatment periods

Study Arms (3)

Azelastine, Fluticasone

EXPERIMENTAL

TEST = MP29-02 = Combination product Azelastine Hydrochloride and Fluticasone Propionate nasal spray (= US formulation as used in pivotal studies)

Drug: Azelastine, Fluticasone

Fluticasone mono

ACTIVE COMPARATOR

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

Fluticasone

ACTIVE COMPARATOR

COMP = Fluticasone Propionate Nasal Spray, Roxane Laboratories = FLU mono Fluticasone propionate nasal spray (= US marketed product)

Drug: Fluticasone

Interventions

Azelastine, Fluticasone DRUG

TEST = MP29-02 = Combination product Azelastine Hydrochloride and Fluticasone Propionate nasal spray (= US formulation as used in pivotal studies)

Azelastine, Fluticasone

Fluticasone mono DRUG

REF = FLU mono Fluticasone Propionate nasal spray (= essentially combination product formulation without any AZE; US FLU mono formulation as used in pivotal studies)

Fluticasone mono

Fluticasone DRUG

COMP = Fluticasone Propionate Nasal Spray, Roxane Laboratories = FLU mono Fluticasone propionate nasal spray (= US marketed product)

Fluticasone

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• MEDA Pharma GmbH & Co. KG: lead
• ClinResearch, GmbH: collaborator
• Prolytic GmbH: collaborator
• pharm-analyt GmbH: collaborator

Study Sites (1)

ClinPharmCologne

Cologne, North Rhine-Westphalia, 51063, Germany

Location

MeSH Terms

Conditions

Rhinitis, Allergic

Interventions

azelastine; Fluticasone

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Christine Kolb

  MEDA Pharma GmbH & Co. KG

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2010
• First Posted: September 3, 2010
• Study Start: August 1, 2010
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: February 7, 2022

Record last verified: 2016-04

Locations

DE (1)