A Manufacturing Transfer Study Comparing the Bioequivalence of a Single Oral Dose of Claritin-D 12-Hour Extended Release Tablet From 2 Different Manufacturers Under Fasted Conditions in Healthy Adult Subjects

Study Overview
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Brief Summary
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To evaluate the bioequivalence of one extended release combination (loratadine 5 mg/pseudoephedrine sulfate 120 mg) tablet manufactured for Bayer HealthCare LLC by SAG Manufacturing, S.L.U. Madrid, Spain (test treatment) to the extended release combination (loratadine 5 mg/pseudoephedrine sulfate 120 mg) tablet manufactured for Bayer SA-NV by Schering-Plough Labo NV Heist (reference treatment) which is currently marketed in Europe.

Official Title
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A Randomized, Crossover Manufacturing Transfer Study Comparing the Bioequivalence of a Single Oral Dose of Claritin-D® 12-Hour Extended Release Tablet (Loratadine 5mg/Pseudoephedrine Sulfate 120 mg, Manufacturer-SAG) to a Single Oral Dose of Claritin-D® 12-Hour Extended Release Tablet (Loratadine 5 mg/Pseudoephedrine Sulfate 120 mg, Manufacturer-Heist) Under Fasted Conditions in Healthy Adult Subjects

Conditions
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Clinical Pharmacology

Intervention / Treatment
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* Drug: Loratadine + Pseudoephedrine sulfate (Claritin-D, BAY818725) (Manufacturer-SAG)
* Drug: Loratadine + Pseudoephedrine sulfate (Claritin-D, BAY818725) (Manufacturer-Heist)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult men or women Age 18 to 55 years inclusive Body mass index 18.5 to 30.0 kg/m*2 inclusive Exclusion Criteria: Positive alcohol or drug screen at Screening or on Day -1 of each dosing period; Use of within 1 month before first study drug administration, systemic or topical medicines or substances which might affect the study objectives, any drug known to induce cytochrome P3A4/5 or P Glycoprotein (e.g., rifampin, carbamazepine, St. John's wort); Any drug known to inhibit cytochrome P3A4/5 or P Glycoprotein (e.g., clarithromycin, chloramphenicol, ketoconazole); History of hypersensitivity symptoms with the use of loratadine, desloratadine (Clarinex), or pseudoephedrine; Females who are pregnant or lactating Known severe allergies (e.g., allergies to more than 3 allergens, allergies affecting the lower respiratory tract - allergic asthma, allergies requiring therapy with corticosteroids); More than moderate alcohol consumption (>40 g of alcohol regularly per day); Any history or suspicion of barbiturate, amphetamine, benzodiazepine, cocaine, opiates, methamphetamine or cannabis abuse; Loss of blood of 50 mL to 499 mL within 30 days of the first dose of trial treatment, or in excess of 500 mL within 56 days of the first dose of trial treatment (e.g., donation, plasmapheresis or injury)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test treatment<br>Healthy adult subjects under fasted conditions | Drug: Loratadine + Pseudoephedrine sulfate (Claritin-D, BAY818725) (Manufacturer-SAG)<br>* Oral, Loratadine 5 mg/ pseudoephedrine sulfate 120 mg (x1)<br>Drug: Loratadine + Pseudoephedrine sulfate (Claritin-D, BAY818725) (Manufacturer-Heist)<br>* Oral, Loratadine 5 mg/ pseudoephedrine sulfate 120 mg (x1)<br>|
| Active Comparator: Reference treatment<br>Healthy adult subjects under fasted conditions | Drug: Loratadine + Pseudoephedrine sulfate (Claritin-D, BAY818725) (Manufacturer-SAG)<br>* Oral, Loratadine 5 mg/ pseudoephedrine sulfate 120 mg (x1)<br>Drug: Loratadine + Pseudoephedrine sulfate (Claritin-D, BAY818725) (Manufacturer-Heist)<br>* Oral, Loratadine 5 mg/ pseudoephedrine sulfate 120 mg (x1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-tlast) of loratadine and pseudoephedrine | Area under the curve from time 0 to the last measurable concentration. | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| Cmax of loratadine and pseudoephedrine | Maximum observed plasma level | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CL/F for loratadine, pseudoephedrine and desloratadine | Total body oral clearance | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| Number of participants with adverse event |  | Up to 26 days | 
| %AUC(tlast-∞) for loratadine, pseudoephedrine and desloratadine | Percentage of AUC from last data point > lower limit of quantification (LLOQ) to infinity | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| Tmax for loratadine, pseudoephedrine and desloratadine | Time at which Cmax is observed | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| Tlast for loratadine, pseudoephedrine and desloratadine | Time point for last measurable concentration. | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| λz for loratadine, pseudoephedrine and desloratadine | Terminal elimination rate constant | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| t1/2 for loratadine, pseudoephedrine and desloratadine | Half-life | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| AUC(0-tlast) for desloratadine | Area under the curve from time 0 to the last measurable concentration. | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| Cmax for desloratadine | Maximum observed plasma level | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 
| AUC for loratadine, pseudoephedrine and desloratadine | Area under the curve from time 0 to infinity. | Baseline (within 60 minutes of dosing) and at 15, 30, 45, 60 minutes and 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose in each treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Upper respiratory allergy symptoms including congestion