type 2 diabetes mellitus tuberculosis bedaquiline comorbidity drug resistance
Conditions
Interventions
single dose 200 mg PO bedaquiline
Sponsors
University Medical Center Groningen
Eligibility
Inclusion criteria
Inclusion criteria: Healthy volunteers must meet all of the following criteria In order to be eligible to participate in this study: - Between 18 and 50 years of age - BMI between 18,5 and 30 (Kg/m2) - Written informed consent T2DM patients must meet all of the following criteria in order to be eligible to participate in this study: - Diagnosed with T2DM - Using metformin with or without an SUD, or solely a SUD. - Between 18 and 50 years of age - BMI between 18,5 and 40 (Kg/m2) - Written informed consent
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: - Drug hypersensitivity to bedaquiline. - History of cardiovascular disease. - Hypokalemia (<3,5 mmol/L). - eGFR<30 ml/min. - Drugs with pro-arrhythmic potential or QT-prolongation. - Pregnant women, breastfeeding women and women of child-bearing potential who are not using reliable contraception. - Participation in any clinical investigation within 3 months prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. - Donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing - Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study medication including, but not limited to any of the following: - Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection - Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months - Pancreatic injury or pancreatitis within the last six months - Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at inclusion visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt. - Inducers and inhibitors of the cytochrome P-450 3A4 isoenzyme (CYP3A4)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A population approach PK model will be developed, describing the plasma bedaquiline concentrations over time. The pharmacokinetic endpoints reported depend on the model structure that describes the data best, but will include model parameters (e.g. volumes of distribution, clearances) and model derived parameters for exposure when appropriate (e.g. the area under the plasma concentration-time curve from zero to infinity, the maximum plasma concentration, time to reach maximum plasma concentration, half-life) | — |
Secondary
| Measure | Time frame |
|---|---|
| When appropriate, covariates will be identified (e.g. CYP3A4 phenotype or bodyweight) that explain inter-individual variability. Particular focus will lie on identifying the covariates CYP3A4 phenotype, disease status (T2DM vs. healthy controls), HbA1C, UACR and type of medication (e.g. metformin vs. SUD). | — |
Contacts
Public ContactJasper Stevens
Dept Clinical Pharmacy and Pharmacology, University Medical Center Groningen
Outcome results
None listed