Seasonal Allergic Rhinitis
Conditions
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.
Interventions
DRUG140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
It will be nasaly administered
Sponsors
Humanis Saglık Anonim Sirketi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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 * study. * 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 * or limit the ability to comply with protocol requirements. * The subject is able to understand and willing to sign the informed consent form. * For female subjects: negative pregnancy test and the woman is using two reliable contraception * methods & should be non-lactating. * The subject has normal cardiovascular system and ECG recording. * The subject kidney and liver (AST & ALT enzymes) functions tests are within normal range.
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. * The subject has taken a prescription medication within two weeks or even an over the counter * product (OTC) within one week before dosing in each study period and any time during the study, * unless otherwise judged acceptable by the clinical investigator. * The subject has taken grapefruit containing beverages or foodstuffs within seven (7) days before * first dosing and any time during the study. * The subject has been participating in any clinical study (e.g. pharmacokinetics, bioavailability and * bioequivalence studies) within the last 80 days prior to the present study. * The subject has donated blood within 80 days before first dosing. * The subject has a history or presence of cardiovascular, pulmonary, renal, hepatic, gastrointestinal, * hematological, endocrinal, immunological, dermatological, neurological, musculoskeletal or * psychiatric diseases. * The subject has consumed drugs that may affect pharmacological or pharmacokinetic properties * (ritonavir, cobicistat & CNS depressants) two weeks before dosing, during the study and two * weeks after dosing. * The subject has recent nose surgery or a history of chronic sinusitis, recent URTI and nasal septum * deviation that may affect nasal mucosa integrity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) of Beclomethasone dipropionate and its active metabolite Beclomethasone 17-monopropionate | 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Obtaining the Tmax (Time to reach maximum concentration) | 23 hours | The descriptive statistics including Maximum, Minimum and Median values will be measured for Tmax. |
| Temperature (safety and tolerability) | At 1 hour pre-dosing and 2, 6, 10, 14, 18, 22 and 23 hours post dosing, | Clinically significant abnormal deviations. The temperature will be measured axillary, orally or using infrared thermometer, standardized across all subjects. Normal range of temperature 36.5-37.5 ºC. |
| Blood pressure (safety and tolerability) | At 1 hour pre-dosing and 2, 4, 6, 8, 12, and 23 hours post dosing, | Clinically significant abnormal deviations. Normal range of blood pressure \> 90/60 and \<140/90 mmHg. Treatment will be offered to those subjects whom blood pressure drops to 90/60 mm Hg or less and the subject will be excluded in case of not responding to treatment. |
| Pulse (safety and tolerability) | At 1 hour pre-dosing and 2, 4, 6, 8, 12, and 23 hours post dosing, | Clinically significant abnormal deviations. Normal range of Pulse 60-100 Bpm. |
Countries
Jordan
Outcome results
None listed