Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin

Morbid Obesity Clinical Trial

Official title:

Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00331565
• Other study ID #: ATORVA-06
• Status: Completed
• Phase: Phase 4
• First received: May 29, 2006
• Last updated: December 2, 2014
• Start date: August 2006
• Est. completion date: December 2010

Study information

• Verified date: December 2014
• Source: University of Oslo School of Pharmacy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

Altered bioavailability of drugs will potentially affect both drug efficacy as well as safety. In patients subjected to bariatric surgery due to morbid obesity the gastro intestinal tract is considerably reconstructed and a change in drug bioavailability is very likely. Getting further knowledge on important mechanisms responsible for altered bioavailability would help in predicting clinically relevant consequences on different drugs.

In the present study we aim to investigate the effect of bariatric surgery on atorvastatin bioavailability. Atorvastatin is subjected to both extensive metabolism and drug transport and will potentially be a good predictor for mechanisms relevant for other drugs as well.

In addition will the expression of different enzymes and transporters be measured in the gastrointestinal tract and in the liver to elucidate on mechanism behind the eventual effects.

Description:

The primary objective of the study is to compare the effect of gastric bypass and BPD+DS operations on atorvastatin bioavailability.

Secondary objectives are to determine the relative change in atorvastatin bioavailability following gastric bypass as well as BPD+DS operations. In addition will the individual CYP3A4, CYP3A5 and P-gp activity in the different organs from where biopsies can be obtained be descriptively compared with atorvastatin pharmacokinetic variables.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Scheduled for bariatric surgery.

• 18 years of age or older.

• Ongoing treatment with statin.

• Able and willing to donate GI-tract and liver biopsies.

• Signed informed consent.

Exclusion Criteria:

• Concomitant treatment with drugs and/or other factors that may influence atorvastatin pharmacokinetics

Study Design

Allocation: Non-Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Morbid Obesity
• Obesity, Morbid

Intervention

Procedure:
• Bariatric surgery
Gastric bypass, duodenal switch and sleeve surgery

Locations

Country	Name	City	State
Norway	Hospital in Vestfold	Tønsberg

Sponsors (2)

Lead Sponsor	Collaborator
University of Oslo School of Pharmacy	The Hospital of Vestfold

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ratio of atorvastatin AUC0-8 between groups		june 2009	No
Secondary	Change in bioavailability of atorvastatin within each surgical technique will be analyzed as ratio of AUC0-8 from before to after surgery in accordance to the bioequivalence criteria of 80-125%.		june 2009	No
Secondary	Descriptive comparison of mRNA expression of CYP3A4, CYP3A5, P-gp and OATP1B1 in different biopsies and atorvastatin and metabolites pharmacokinetics.		june 2009	No
Secondary	Descriptive comparison of protein expression of CYP3A4, CYP3A5 and P-gp in different biopsies and atorvastatin and its metabolites pharmacokinetics.		december 2009	No
Secondary	Descriptive listing of atorvastatin and metabolites concentrations in patients with different genotypes analyzed. It is anticipated that an exploratory analysis will be performed to compare the groups.		june 2009	No
Secondary	Descriptive listing of the relationship between plasma and skeletal muscle as well as adipose tissue concentrations of atorvastatin and metabolites.		december 2009	No
Secondary	Adverse events and serious adverse events will be listed.		june 2009	Yes