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

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

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.

Study Overview

• Status: Completed
• Conditions: Clinical Pharmacology
• Intervention / Treatment: Drug: Loratadine + Pseudoephedrine sulfate (Claritin-D, BAY818725) (Manufacturer-SAG); Drug: Loratadine + Pseudoephedrine sulfate (Claritin-D, BAY818725) (Manufacturer-Heist)

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Secaucus, New Jersey, United States, 07094
      • Frontage Clinical Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2018
• Primary Completion (Actual): July 20, 2018
• Study Completion (Actual): July 20, 2018

Study Registration Dates

• First Submitted: April 16, 2018
• First Submitted That Met QC Criteria: April 27, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): September 19, 2018
• Last Update Submitted That Met QC Criteria: September 18, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Upper respiratory allergy symptoms including congestion
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Central Nervous System Stimulants; Sympathomimetics; Histamine H1 Antagonists, Non-Sedating; Vasoconstrictor Agents; Nasal Decongestants; Ephedrine; Pseudoephedrine; Loratadine
• Other Study ID Numbers: 19625

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No