Clinical trial NCT01642862: Study for Identifying Optimal Simvastatin Formulation for Uniform Time to Maximum Plasma Concentration
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Celiac Disease
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Stanford University
First posted: 2012-07-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Peak plasma concentration (Cmax) of simvastatin
timeFrame: 0, 15, 30, 60, 90, 120, 180 minutes post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, University Hospital Zurich, Gastroenterology and Hepatology
state: ZH
Study officials:
affiliation: University Hospital Zurich, Gastroenterology and Hepatology
name: Gerhard Rogler, Prof MD PhD
role: PRINCIPAL_INVESTIGATOR
References: