An Open Label, Randomized, Three-treatment, Three-period, Crossover, Single Dose Study, to Investigate Drug-drug Interaction and Relative Bioavailability Between the Fixed Dose Combination Azelastine Hydrochloride / Beclomethasone Dipropionate (140/100 μg Azelastine Hydrochloride / Beclomethasone Dipropionate) Nasal Spray, and Beclomethasone Dipropionate Nasal Spray (100 μg Beclomethasone Dipropionate) in the Test Vehicle, and the Commercially Available Product, RinoClenil® Nasal Spray (100 μg Beclomethasone Dipropionate), in Healthy Subjects Under Fasting Conditions
Overview
- Phase
- Phase 1
- Intervention
- 140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
- Conditions
- Seasonal Allergic Rhinitis
- Sponsor
- Humanis Saglık Anonim Sirketi
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Maximum observed plasma concentration (Cmax) of Beclomethasone dipropionate and its active metabolite Beclomethasone 17-monopropionate
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
An open label, randomized, three-treatment, three-period, crossover, single dose study, to investigate drug-drug interaction and relative bioavailability between the fixed dose combination Azelastine hydrochloride / Beclomethasone dipropionate (140/100 μg Azelastine hydrochloride / Beclomethasone dipropionate) Nasal Spray, and Beclomethasone Dipropionate Nasal Spray (100 μg Beclomethasone Dipropionate) in the test vehicle, and the commercially available product, RinoClenil® Nasal Spray (100 μg Beclomethasone Dipropionate), in healthy subjects under fasting conditions.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The subject is Caucasian \& aged between eighteen \& fifty years (18 - 50), both inclusive.
- •The subject is within the limits for his height \& weight as defined by the body mass index range
- •(18.5 - 30.0 Kg/m2).
- •The subject is willing to undergo the necessary pre- \& post- medical examinations set by this
- •The results of medical history, vital signs, physical examination \& conducted medical laboratory
- •tests are normal as determined by the clinical investigator.
- •The subject tested negative for hepatitis (HBsAg, HCVAb) viruses and human immunodeficiency
- •virus (HIVAb).
- •There is no evidence of psychiatric disorder, antagonistic personality and poor motivation,
- •emotional or intellectual problems likely to limit the validity of consent to participate in the study
Exclusion Criteria
- •The subject is smoker/ has positive cotinine test.
- •The subject has suffered an acute illness one week before dosing.
- •The subject has a history of or concurrent abuse of alcohol.
- •The subject has a history of or concurrent abuse of illicit drugs.
- •The subject has a history of hypersensitivity and/or contraindications to the study drug, its
- •excipients and any related compounds.
- •The subject has been hospitalized within three months before the study or during the study.
- •The subject is vegetarian.
- •The subject has consumed caffeine or xanthine containing beverages or foodstuffs within two days
- •before dosing and until 23 hours after dosing in all study periods.
Arms & Interventions
140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
Intervention: 140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
100 μg Beclomethasone dipropionate, Nasal Spray
Intervention: 140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
RinoClenil® Nasal Spray (100 μg Beclomethasone Dipropionate)
Intervention: 140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
Outcomes
Primary Outcomes
Maximum observed plasma concentration (Cmax) of Beclomethasone dipropionate and its active metabolite Beclomethasone 17-monopropionate
Time Frame: 23 hours
For the assessment of a potential drug-drug interaction, no effect of Azelastine on the pharmacokinetics of Beclomethasone dipropionate and its active metabolite Beclomethasone 17-monopropionate will be concluded if the fixed dose combination Test-to-mono test GMR and the corresponding 90% CI of the ln-transformed primary pharmacokinetic parameters are within the 80.00% to 125.00% acceptance interval. For the assessment of the relative bioavailability, bioequivalence between Beclomethasone dipropionate drug products will be concluded if the fixed dose combination test-to-mono reference GMR and the corresponding 90% CI of the Lntransformed primary pharmacokinetic parameters are within the 80.00% to 125.00% acceptance interval.
area under the plasma concentration versus time curve (AUC) from pre-dose (time zero) to the last sampling time with quantifiable concentrations (AUC0-t) of Beclomethasone dipropionate and its active metabolite Beclomethasone 17-monopropionate
Time Frame: 23 hours
For the assessment of a potential drug-drug interaction, no effect of Azelastine on the pharmacokinetics of Beclomethasone dipropionate and its active metabolite Beclomethasone 17-monopropionate will be concluded if the fixed dose combination Test-to-mono test GMR and the corresponding 90% CI of the ln-transformed primary pharmacokinetic parameters are within the 80.00% to 125.00% acceptance interval. For the assessment of the relative bioavailability, bioequivalence between Beclomethasone dipropionate drug products will be concluded if the fixed dose combination test-to-mono reference GMR and the corresponding 90% CI of the Lntransformed primary pharmacokinetic parameters are within the 80.00% to 125.00% acceptance interval.
AUC from time zero to infinity (AUC0-∞) of Beclomethasone dipropionate and its active metabolite Beclomethasone 17-monopropionate
Time Frame: 23 hours
For the assessment of a potential drug-drug interaction, no effect of Azelastine on the pharmacokinetics of Beclomethasone dipropionate and its active metabolite Beclomethasone 17-monopropionate will be concluded if the fixed dose combination Test-to-mono test GMR and the corresponding 90% CI of the ln-transformed primary pharmacokinetic parameters are within the 80.00% to 125.00% acceptance interval. For the assessment of the relative bioavailability, bioequivalence between Beclomethasone dipropionate drug products will be concluded if the fixed dose combination test-to-mono reference GMR and the corresponding 90% CI of the Lntransformed primary pharmacokinetic parameters are within the 80.00% to 125.00% acceptance interval.
Secondary Outcomes
- Obtaining the Tmax (Time to reach maximum concentration)(23 hours)
- Pulse (safety and tolerability)(At 1 hour pre-dosing and 2, 4, 6, 8, 12, and 23 hours post dosing,)
- Blood pressure (safety and tolerability)(At 1 hour pre-dosing and 2, 4, 6, 8, 12, and 23 hours post dosing,)
- Temperature (safety and tolerability)(At 1 hour pre-dosing and 2, 6, 10, 14, 18, 22 and 23 hours post dosing,)