Study for Identifying Optimal Simvastatin Formulation for Uniform Time to Maximum Plasma Concentration

Study Overview
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Brief Summary
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The inter- and intra-variability in the pharmacokinetic parameters of different formulations and doses of simvastatin in healthy subjects and in subjects with celiac disease in remission will be evaluated. Additionally, baseline values of pharmacokinetic parameters of simvastatin for both study groups will be determined.

Official Title
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A Phase I, Randomized, Open Label, Mono-centered, Prospective Study to Evaluate the Pharmacokinetics of Different Formulations and Doses of Simvastatin in Healthy Subjects and in Subjects With Celiac Disease in Remission

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: If the subject is female, she is eligible to enter and participate in this study if she is physiologically incapable of becoming pregnant or has a negative urine pregnancy test at screening and at baseline visit Negative Serology for Hepatitis B/C, HIV Non-OATP1B1*5 carriers Negative Serology for anti-transglutaminase IgA antibody, and normal levels of total IgA For subjects with celiac disease, also Diagnosis of celiac disease confirmed by medical history, histological evaluation of small intestinal mucosa on small bowel biopsy, and abnormal anti-transglutaminase antibody titers Followed a gluten-free diet for at least one year, as verified by normal anti-transglutaminase antibody levels, Marsh 0-1 score on a follow-up biopsy within the past 12 months, and absence of any clinical signs or symptoms of celiac disease observed at diagnosis Exclusion criteria: Current smoker or quit smoking less than 2 years ago Female breastfeeding or disagrees to use an effective mechanical contraceptive method (e.g. diaphragm or nonhormonal intrauterine device in combination with preservative) Presence of any known on-going disease which is judged to be relevant according to the investigator, besides celiac disease for the cohort of celiac patients in remission State after operations of the stomach or bowel (exception: appendectomy) Participation in any other clinical trial with investigational or approved drugs within the last month before the study Regular alcohol consumption of more than 25 g / day Use of any prescription or non-prescription drugs (including herbal supplements) must be discontinued 30 days prior to study (exceptions: paracetamol and NSAIDs, not taken longer than 2 days in a row and not taken within the last 3 days before the study) Consumption of grapefruit, star fruit, grapefruit juice, or star fruit juice must be discontinued 7 days prior to the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liquid formulation of Simvastatin<br> | Drug: Simvastatin<br>* Comparison of pharmacokinetic parameters of different formulations (liquid vs tablet) and doses (20 or 40 mg) of simvastatin after single oral administration of the drug<br>|
| Active Comparator: Tablet formulation of Simvastatin<br> | Drug: Simvastatin<br>* Comparison of pharmacokinetic parameters of different formulations (liquid vs tablet) and doses (20 or 40 mg) of simvastatin after single oral administration of the drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) of simvastatin | Determination of time-dependent concentrations of simvastatin in collected serum of each subject following oral administration of two different formulations and two different doses of simvastatin | 0, 15, 30, 60, 90, 120, 180 minutes post-dose |