To Investigate Drug-drug Interaction and Relative Bioavailability Between the FDC AzelastineHCL/Beclomethasone Dipropionate Nasal Spray, & Beclomethasone Dipropionate Nasal Spray in the Test Vehicle, and RinoClenil® Nasal Spray
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
|
Drug: 140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
It will be nasaly administered
Other Names:
|
| Experimental: 100 μg Beclomethasone dipropionate, Nasal Spray
|
Drug: 140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
It will be nasaly administered
Other Names:
|
| Active Comparator: RinoClenil® Nasal Spray (100 μg Beclomethasone Dipropionate)
|
Drug: 140/100 μg Azelastine hydrochloride/Beclomethasone Dipropionate)
It will be nasaly administered
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Obtaining the Tmax (Time to reach maximum concentration) [23 hours]
The descriptive statistics including Maximum, Minimum and Median values will be measured for Tmax.
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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The subject is Caucasian & aged between eighteen & fifty years (18 - 50), both inclusive.
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The subject is within the limits for his height & weight as defined by the body mass index range
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(18.5 - 30.0 Kg/m2).
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The subject is willing to undergo the necessary pre- & post- medical examinations set by this
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study.
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The results of medical history, vital signs, physical examination & conducted medical laboratory
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tests are normal as determined by the clinical investigator.
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The subject tested negative for hepatitis (HBsAg, HCVAb) viruses and human immunodeficiency
-
virus (HIVAb).
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There is no evidence of psychiatric disorder, antagonistic personality and poor motivation,
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emotional or intellectual problems likely to limit the validity of consent to participate in the study
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or limit the ability to comply with protocol requirements.
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The subject is able to understand and willing to sign the informed consent form.
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For female subjects: negative pregnancy test and the woman is using two reliable contraception
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methods & should be non-lactating.
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The subject has normal cardiovascular system and ECG recording.
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The subject kidney and liver (AST & ALT enzymes) functions tests are within normal range.
Exclusion Criteria:
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The subject is smoker/ has positive cotinine test.
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The subject has suffered an acute illness one week before dosing.
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The subject has a history of or concurrent abuse of alcohol.
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The subject has a history of or concurrent abuse of illicit drugs.
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The subject has a history of hypersensitivity and/or contraindications to the study drug, its
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excipients and any related compounds.
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The subject has been hospitalized within three months before the study or during the study.
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The subject is vegetarian.
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The subject has consumed caffeine or xanthine containing beverages or foodstuffs within two days
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before dosing and until 23 hours after dosing in all study periods.
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The subject has taken a prescription medication within two weeks or even an over the counter
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product (OTC) within one week before dosing in each study period and any time during the study,
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unless otherwise judged acceptable by the clinical investigator.
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The subject has taken grapefruit containing beverages or foodstuffs within seven (7) days before
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first dosing and any time during the study.
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The subject has been participating in any clinical study (e.g. pharmacokinetics, bioavailability and
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bioequivalence studies) within the last 80 days prior to the present study.
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The subject has donated blood within 80 days before first dosing.
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The subject has a history or presence of cardiovascular, pulmonary, renal, hepatic, gastrointestinal,
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hematological, endocrinal, immunological, dermatological, neurological, musculoskeletal or
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psychiatric diseases.
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The subject has consumed drugs that may affect pharmacological or pharmacokinetic properties
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(ritonavir, cobicistat & CNS depressants) two weeks before dosing, during the study and two
-
weeks after dosing.
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The subject has recent nose surgery or a history of chronic sinusitis, recent URTI and nasal septum
-
deviation that may affect nasal mucosa integrity.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ACDIMA Biocenter | Amman | Jordan |
Sponsors and Collaborators
- Pharmactive Ilac Sanayi ve Tic A.S.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 980-2020