Pharmacometabolomics of Andrographis Paniculata And Metformin In Healthy Volunteers Under Fasting Condition

Pharmacokinetics Clinical Trial

Official title:

A Phase 1, Open Label, Randomized, Three-Period, Crossover, Single Dose Oral Administration Of Andrographis Paniculata And Metformin Clinical Trial In Healthy Volunteers Under Fasting Condition

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04161404
• Other study ID #: P1-PKPD-Metabolomic
• Status: Recruiting
• Phase: Phase 1
• Start date: August 21, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: December 2019
• Source: University of Malaya
• Contact: Krisna Veni Balakrishnan
• Phone: 60379494932
• Email: krisna.veni[@]ummc.edu.my
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Sex: male

2. 18 to 45 years of age (inclusive both)

3. BMI 18.5 - 29.5 kg/m2 (inclusive both) with minimum weight of 50kg

4. Non-smokers

5. Legible and willing to provide written informed consent.

Exclusion Criteria:

1. Volunteers suffering from any chronic illness such as arthritis, asthma, etc.

2. History of pre-existing bleeding disorder.

3. Clinically relevant abnormalities in the results of the laboratory screening evaluation.

4. Clinically significant abnormal electrocardiogram (ECG).

5. Positive HIV or positive hepatitis B or C in screening test or no known other hepatitis infection.

6. History of significant blood loss due to any reason, including blood donation in the past 3 months.

7. Participation in any study within past 3 months

8. History of alcohol or drug abuse

9. History of consumption of prescribed medication since last 14 days or Over-the-counter medication/ herbal remedies since last 7 days before beginning of the study.

10. Systolic blood pressure less than 100 mmHg or more than 139 mmHg and diastolic blood pressure less than 60 mmHg or more than 89 mmHg.

11. Pulse rate less than 60/minutes or more than 100/minute unless deem not clinically significant by investigator.

12. Oral temperature more than 37.5 degree Celsius.

13. History of allergy to the investigational product or any drug chemically similar to the drug under investigation.

14. Recent history of kidney or liver dysfunction.

15. Volunteers suffering from any psychiatric (acute or chronic) disorder.

16. Existence of any surgical or medical condition, which, in the judgment of the chief investigator and/or clinical investigator/physician, might interfere with the absorption, distribution, metabolism or excretion of the drug or likely to compromise the safety of volunteers.

17. Inability to communicate or co-operate.

Related Conditions & MeSH terms

• Molecular Mechanisms of Pharmacological Action
• Pharmacokinetics

Intervention

Drug:
• Brand name: Andrographis paniculata (Shine Hempedu Bumi) 1000mg capsules
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.
• Brand name: Andrographis paniculata (Shine Hempedu Bumi) 2000mg
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.
• Metformin (Glucophage) 1000mg
Metformin is an oral glucose-lowering drug of the biguanides class. Drug: Period 1 Subjects

Locations

Country	Name	City	State
Malaysia	Clinical Investigation Centre, University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur

Sponsors (2)

Lead Sponsor	Collaborator
University of Malaya	Ministry of Health, Malaysia

Country where clinical trial is conducted

Malaysia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve (AUC) of Andrographis paniculata	Area under the plasma concentration curve of Andrographis paniculata from administration to 24 hours	0-24 hours
Primary	Cmax of Andrographis paniculata	Maximum plasma concentration of Andrographis paniculata after single dose oral administration.	0-24 hours
Primary	Tmax of Andrographis paniculata	Time until Cmax of Andrographis paniculata is reached after single dose oral administration.	0-24 hours
Primary	Area under the plasma concentration-time curve (AUC) of Metformin	Area under the plasma concentration curve of Metformin from administration to 24 hours	0-24 hours
Primary	Cmax of Metformin	Maximum plasma concentration of Metformin after single dose oral administration.	0-24 hours
Primary	Tmax of Metformin	Time until Cmax of Metformin is reached after single dose oral administration.	0-24 hours
Secondary	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.	24 hours
Secondary	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.	24 hours
Secondary	Adverse drug reaction	Number of subjects with adverse drug reaction	3 weeks

External Links

•   Medical Research Ethics Committee, University Malaya Medical Centre
•   Research Facility: Clinical Investigation Centre, University Malaya Medical Centre