This study is a phase 1, open label, randomized, three-way crossover, single dose, oral- administration of Andrographis paniculata and Metformin in healthy volunteers under fasting condition. The study will demonstrate the pharmacokinetics profile and pharmacodynamic through metabolic pathway analysis for Andrographis paniculata and Metformin.
This is a phase 1, open label, randomized, three period, crossover, single dose oral administration of Andrographis Paniculata 1000mg, 2000mg and Metformin 1000mg clinical trial in healthy volunteers under fasting condition. Approximately 18 healthy volunteers will be enrolled into this study. The healthy volunteers will be screened for inclusion and exclusion criteria. Eligible subjects will be enrolled into either Metformin 1000mg tablet, Andrographis Paniculata 1000mg or 2000mg capsule in a ratio of 1:1:1 in period 1 for single dose oral administration. Subjects will then undergo a washout period of at least 7 days. After the washout period, subjects will crossover over to another investigational product according to the randomization sequence. Subjects will fast overnight prior to dosing. The volunteers will be admitted to Clinical Investigation Center ward at 7 am in the morning and will confine in air-conditioning environment with beds and chairs. The means during the stay at CIC ward will be provided to the subjects. The dosing will be performed at 8am. A series of plasma will be collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 and 24 hours post-dose. Urine samples will be collected at 0, 0-4 hours, 4-8 hours and 8-12 hours. A safety follow-up call will be made to subjects to record any adverse events that occurred post-dosing within 1 week.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
18
Andrographis paniculata or hempedu bumi capsule is a traditional medicinal product registered under Ministry of Health Malaysia for general wealth being. It is traditionally used for anti-diabetic, anti-bacterial, anti-pyretic, anti-malarial, anti-inflammatory, antidiarrhoeal and other effects.
Andrographis paniculata or hempedu bumi capsule is a traditional medicinal product registered under Ministry of Health Malaysia for general wealth being. It is traditionally used for anti-diabetic, anti-bacterial, anti-pyretic, anti-malarial, anti-inflammatory, antidiarrhoeal and other effects.
Clinical Investigation Centre, University Malaya Medical Centre
Kuala Lumpur, Kuala Lumpur, Malaysia
RECRUITINGArea under the plasma concentration-time curve (AUC) of Andrographis paniculata
Area under the plasma concentration curve of Andrographis paniculata from administration to 24 hours
Time frame: 0-24 hours
Cmax of Andrographis paniculata
Maximum plasma concentration of Andrographis paniculata after single dose oral administration.
Time frame: 0-24 hours
Tmax of Andrographis paniculata
Time until Cmax of Andrographis paniculata is reached after single dose oral administration.
Time frame: 0-24 hours
Area under the plasma concentration-time curve (AUC) of Metformin
Area under the plasma concentration curve of Metformin from administration to 24 hours
Time frame: 0-24 hours
Cmax of Metformin
Maximum plasma concentration of Metformin after single dose oral administration.
Time frame: 0-24 hours
Tmax of Metformin
Time until Cmax of Metformin is reached after single dose oral administration.
Time frame: 0-24 hours
Metabolic pathway of Andrographis paniculata
Pre-dose and post-dose samples will be analysed using LCMSMS. Normalization, log-transformation and center scaling will then apply to batches of chromatograms. Global metabolomics analyses will be performed to identify significant endogenous metabolites between post-dose and pre-dose samples using T-Test, Principal Component Analysis, Partial Least Square Discriminant Analysis. Annotations of significant compounds will be perform using METLIN database. The significant compounds will lead to prediction of relevant metabolomic pathway from Human Metabolome Database/ Kyoto Encyclopedia of Gene and Genome pathway for Andrographis paniculata.
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Metformin is an oral glucose-lowering drug of the biguanides class. Drug: Period 1 Subjects
Time frame: 24 hours
Metabolic pathway of Metformin
Pre-dose and post-dose samples will be analysed using LCMSMS. Normalization, log-transformation and center scaling will then apply to batches of chromatograms. Global metabolomics analyses will be performed to identify significant endogenous metabolites between post-dose and pre-dose samples using T-Test, Principal Component Analysis, Partial Least Square Discriminant Analysis. Annotations of significant compounds will be perform using METLIN database. The significant compounds will lead to prediction of relevant metabolomic pathway from Human Metabolome Database/ Kyoto Encyclopedia of Gene and Genome pathway for Metformin.
Time frame: 24 hours
Adverse drug reaction
Number of subjects with adverse drug reaction
Time frame: 3 weeks