No registrations found.
ID
Source
Brief title
Health condition
type 2 diabetes mellitus
tuberculosis
bedaquiline
comorbidity
drug resistance
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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).
Study objective
It is well documented that T2DM patients have altered pharmacokinetics due to disease related changes in absorption, distribution and metabolic processes. As such, T2DM may thus affect bedaquiline exposure which may result in reduced efficacy. In this study we will evaluate, for the first time, the pharmacokinetics of bedaquiline in patients with comorbid T2DM
Study design
Venous blood samples will be taken at screening and pre-dose (2 samples of 10 mL) and will be assessed for clinical chemistry and laboratory assessment.
Prior to dosing an oral swab will be obtained for genotyping.
Blood samples of 4 mL will be collected at t=0, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48 and 72h after administration of bedaquiline for quantification of total plasma concentration of bedaquiline.
Morning urine voids will be collected on all three study days in order to determine the urinary albumin:creatinine ratio.
Intervention
single dose 200 mg PO bedaquiline
Jasper Stevens
Groningen
The Netherlands
050-361-7875
j.stevens@umcg.nl
Jasper Stevens
Groningen
The Netherlands
050-361-7875
j.stevens@umcg.nl
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
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
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL6867 |
| NTR-old | NTR7045 |
| Other | 201700787 : 2017-004490-14 |