Impact of Two Genetic Variants of OATP1B3 or MRP2 or Rifampin on Systemic Disposition and Biological Efficacy of CCK-8
Phase 1
Completed
- Conditions
- Gastrointestinal Hormones
- Interventions
- Dietary Supplement: mixed meal
- Registration Number
- NCT02507167
- Lead Sponsor
- University Medicine Greifswald
- Brief Summary
The purpose of this study is to evaluate the impact of genetic variants of OATP 1B3 or MRP 2 on the systemic disposition of endogenously formed CCK-8 and to determine the influence of a single-dose of the transporter inhibitor rifampin (600 mg) on the systemic disposition of endogenously formed CCK-8. Endogenous CCK-8 secretion will be induced by a single-dose standardized liquid mixed meal.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 19
Inclusion Criteria
- age: 18-45 years
- sex: male
- 12 subjects being homozygote wild-type carriers of OATP 1B3 (c.SLCO 1B3 699 AA and c.SLCO 1B3 334 GG) and MRP 2
- 12 subjects being homozygotes of the MRP 2 variants (genetic loss of function) and homozygote wild-type carriers of OATP 1B3
- 12 subjects being homozygotes of the OATP 1B3 variants (c.SLCO 1B3 699 GG and c.SLCO 1B3 334 TT) and homozygotes wild-type carriers of MRP 2
- BMI: ≥ 19 kg/m2 and ≤ 27 kg/m2
- good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which will be judged by the clinical investigator not to differ in a clinical relevant way from the healthy state
- written informed consent given by the volunteer after being provided with detailed information (both, verbally and written) about the nature, risks, and scope of the clinical trial as well as the expected desirable and adverse effects of the drug
Exclusion Criteria
- hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication
- gastrointestinal diseases and/or pathological findings (e.g. stenoses), which might interfere with pharmacokinetics and pharmacodynamics of the study medication
- subjects with existing dysfunction in regulation of glucose metabolism, e.g. deficiency of glucose-6-phosphate dehydrogenase (Glc-6-P DHG) and/ or pathological findings
- subjects with alcohol and/ or drug dependence and a alcohol consumption more than 20 g alcohol/ day
- excessive smoking (more than 10 cigarettes or equivalents/ day)
- subjects with positive finding of HBsAG, HIV and/ or drugs
- subjects being on a diet (inclusive special or uniform nutritional habits, e.g. vegetarians or undercaloric diet)
- strong coffee and/ or tea consumption (≥ 1 liter a day)
- subjects suspected or known not to follow instructions
- subjects who are unable to understand written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
- subjects liable to orthostatic dysregulation, fainting, or blackout
- subjects who took part in other clinical trials in the last 3 months (blocking time due to another clinical trial with investigational products)
- acute illness less than 14 d in the past
- blood donation within the last 3 months
- any medication within 4 weeks prior to the intended first administration of the study medication which might influence functions of the gastrointestinal tract (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists, proton pump inhibitors, anticholinergics)
- any other medication within 2 weeks prior to the first administration of the study medication or less than 10-time the half-live of the respective drug
- intake of grapefruit containing food or beverages and poppy seeds containing products 14 d prior to the first drug administration until the last blood sampling of the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description mixed meal mixed meal - mixed meal 2 h after single dose rifampin (600 mg) mixed meal - mixed meal 2 h after single dose rifampin (600 mg) Rifampin -
- Primary Outcome Measures
Name Time Method CCK-8 3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal Cholecystokinin amino acid 8 concentration in blood plasma
- Secondary Outcome Measures
Name Time Method GIP 3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal Gastric inhibitory polypeptide concentration in blood plasma
glucagon 3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal glucagon concentration in blood plasma
glucose 3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal glucose concentration in blood plasma
GLP-1 3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal Glucagon-like peptide-1 concentration in blood plasma
potassium 3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal potassium concentration in blood plasma
C-peptide 3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal connecting peptide concentration in blood plasma
insulin 3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal insulin concentration in blood plasma
Trial Locations
- Locations (1)
Department of Clinical Pharmacology
🇩🇪Greifswald, Germany