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

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

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.

Study Overview

• Status: Terminated
• Conditions: Celiac Disease
• Intervention / Treatment: Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • ZH
    • Zurich, ZH, Switzerland, 8091
      • University Hospital Zurich, University Hospital Zurich, Gastroenterology and Hepatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liquid formulation of Simvastatin	Drug: Simvastatin; 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
Active Comparator: Tablet formulation of Simvastatin	Drug: Simvastatin; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Stanford University
• Investigators: Principal Investigator: Gerhard Rogler, Prof MD PhD, University Hospital Zurich, Gastroenterology and Hepatology

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: July 10, 2012
• First Submitted That Met QC Criteria: July 13, 2012
• First Posted (Estimate): July 17, 2012

Study Record Updates

• Last Update Posted (Estimate): June 3, 2015
• Last Update Submitted That Met QC Criteria: June 2, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: CYPCEL-1103