Excipient Effect on Drug Absorption in Humans

Study Overview
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Brief Summary
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The purpose of this study is to determine if sodium lauryl sulfate (SLS), a non-drug ingredient commonly added in drug products, affect absorption of drugs that are given together with the ingredient. Investigators want to find out if drug absorption is different in people taking the drug alone compared to people taking the drug with low and high amounts of sodium lauryl sulfate at the same time.

Detailed Description
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This is a single-center, randomized, double-blind, 3-period crossover trial. Participants will be randomized to receive a Control capsule (fexofenadine single agent) under Treatment Arm 1 or a Test 1 capsule (fexofenadine and 3 mg SLS) under Treatment Arm 2 or Test 2 capsule (fexofenadine and 30 mg SLS) under Treatment Arm 3. Investigators will assess the effect of SLS on the absorption of fexofenadine by measuring SLS and fexofenadine concentrations in plasma and stool samples and determine the change in AUC (area under the curve), Cmax and other pharmacokinetic parameters, between Treatment Arms 2 or 3 and Treatment Arm 1.

Official Title
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The Effect of Sodium Lauryl Sulfate on the Oral Absorption of Fexofenadine in Humans

Conditions
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The Impact of Excipients on Drug Absorption

Intervention / Treatment
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* Drug: Fexofenadine Hydrochloride without sodium lauryl sulfate
* Drug: Fexofenadine Hydrochloride with sodium lauryl sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers of all ethnic groups and races. Male and females between the ages of 18-64 years old, inclusive. Subjects who are willing to avoid ingestion of fruit juices and citrus bioflavonoids, such as grapefruit extract, hesperidin supplement and naringin supplement, for a period extending from one week prior to the initiation of the study until its completion. Written informed consent obtained from the subject and ability for subject to comply with the requirements of the study. Exclusion Criteria: Subjects with extreme obesity (BMI > 35). Subjects who are allergic to fexofenadine or SLS. Subjects who have hemoglobin level lower than 12 g/dL. Subjects who are pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Subjects consuming types of food and supplements with the potential to interfere with the study objectives as judged by the Investigator. Subjects taking any drugs, especially known OATP2B1 substrates (aliskiren, atenolol, celiprolol, fexofenadine, rosuvastatin and ticlopidine, etc.) except birth control hormonal medications. Subjects with a condition, disease, or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. Subjects with any disease affecting or impairing the function of the liver, kidney or heart. Subjects with gastrointestinal disease, gastrointestinal disorder, or gastrointestinal surgery. Subjects with known infection with HIV, Hepatitis B or Hepatitis C (as determined by questionnaire, no laboratory diagnostics concerning these diseases will be performed within the present study). Volunteers who are cured of past Hepatitis C infection are eligible to participate with a doctor's approval letter). Subjects who are smokers or have smoked in the past year and/or have smoked or ingested tetrahydrocannabinol/marijuana in the past week, or who are unwilling to comply throughout the study period. Alcohol use on average > 2 servings/day or > 14 servings/wk (Serving size: 12oz beer/4oz wine/2oz hard liquor) in the past week or self-reported binge drinking. Participating in another research study while participating in this research study. Non-English speaking. Subjects with abnormal laboratory results at Screening Visit as judged by the Investigator or study physician.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a single-center, randomized, double-blind, 3-period crossover trial. Subjects will be randomized to receive fexofenadine only under Treatment Arm 1 or fexofenadine and 3 mg SLS under Treatment Arm 2 or fexofenadine and 30 mg SLS under Treatment Arm 3.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fexofenadine without SLS<br>Participants will be administered by mouth with a capsule containing 120 mg fexofenadine hydrochloride and 101 mg microcrystalline cellulose | Drug: Fexofenadine Hydrochloride without sodium lauryl sulfate<br>* without sodium lauryl sulfate<br>* Other names: Allegra;|
| Experimental: Fexofenadine and 3 mg SLS<br>Participants will be administered by mouth with a capsule containing 120 mg fexofenadine hydrochloride, 3 mg SLS and 101 mg microcrystalline cellulose | Drug: Fexofenadine Hydrochloride with sodium lauryl sulfate<br>* with sodium lauryl sulfate<br>* Other names: Allegra;|
| Experimental: Fexofenadine and 30 mg SLS<br>Participants will be administered by mouth with a capsule containing 120 mg fexofenadine hydrochloride, 30 mg SLS and 101 mg microcrystalline cellulose | Drug: Fexofenadine Hydrochloride with sodium lauryl sulfate<br>* with sodium lauryl sulfate<br>* Other names: Allegra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of Fexofenadine | To determine whether SLS decreases the fexofenadine area under the curve (AUC) between Fexofenadine + 3 mg SLS or Fexofenadine + 30 mg SLS and Fexofenadine only. | 0-48 hours | 
| Maximum Plasma Concentration (Cmax) of Fexofenadine | To determine whether SLS decreases the fexofenadine Cmax between Fexofenadine + 3 mg SLS or Fexofenadine + 30 mg SLS and Fexofenadine only. | 0-48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sodium lauryl sulfate plasma concentration | To determine plasma SLS concentration in order to understand the absorption of SLS in humans | 0-48 hours | 
| Fexofenadine stool amount | To determine stool amount of fexofenadine and compare between the fexofenadine only arm to the 3 mg SLS and the 30 mg SLS arm. | 0-48 hours | 
| Sodium lauryl sulfate stool amount | To determine stool amount of sodium lauryl sulfate and compare between the fexofenadine only arm to the 3 mg SLS and the 30 mg SLS arm. | 0-48 hours |