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

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

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.

Study Overview

• Status: Unknown
• Conditions: Pharmacokinetics; Molecular Mechanisms of Pharmacological Action
• Intervention / Treatment: Drug: Brand name: Andrographis paniculata (Shine Hempedu Bumi) 1000mg capsules; Drug: Brand name: Andrographis paniculata (Shine Hempedu Bumi) 2000mg; Drug: Metformin (Glucophage) 1000mg

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Malaysia
  • Wilayah Persekutuan Kuala Lumpur
    • Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia, 59100
      • Recruiting
      • Clinical Investigation Centre, University Malaya Medical Centre
      • Contact: Krisna Veni Balakrishnan; Phone Number: 60379494932; Email: cic_staff@um.edu.my
      • Principal Investigator: Luqman Ibrahim, MD
      • Sub-Investigator: Khim Boon Tee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1; Subjects will randomized to either of the intervention drug in a ratio of 1:1:1 following three period, cross-over study design.	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.; Other Names: Product name: Shine Hempedu Bumi; Drug: 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.; Other Names: Product name: Shine Hempedu Bumi; Drug: Metformin (Glucophage) 1000mg; Metformin is an oral glucose-lowering drug of the biguanides class. Drug: Period 1 Subjects; Other Names: Brand name: Glucophage
Experimental: Period 2; Subjects will randomized to either of the intervention drug in a ratio of 1:1:1 following three period, cross-over study design.	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.; Other Names: Product name: Shine Hempedu Bumi; Drug: 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.; Other Names: Product name: Shine Hempedu Bumi; Drug: Metformin (Glucophage) 1000mg; Metformin is an oral glucose-lowering drug of the biguanides class. Drug: Period 1 Subjects; Other Names: Brand name: Glucophage
Experimental: Period 3; Subjects will randomized to either of the intervention drug in a ratio of 1:1:1 following three period, cross-over study design.	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.; Other Names: Product name: Shine Hempedu Bumi; Drug: 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.; Other Names: Product name: Shine Hempedu Bumi; Drug: Metformin (Glucophage) 1000mg; Metformin is an oral glucose-lowering drug of the biguanides class. Drug: Period 1 Subjects; Other Names: Brand name: Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Cmax of Andrographis paniculata	Maximum plasma concentration of Andrographis paniculata after single dose oral administration.	0-24 hours
Tmax of Andrographis paniculata	Time until Cmax of Andrographis paniculata is reached after single dose oral administration.	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	0-24 hours
Cmax of Metformin	Maximum plasma concentration of Metformin after single dose oral administration.	0-24 hours
Tmax of Metformin	Time until Cmax of Metformin is reached after single dose oral administration.	0-24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Adverse drug reaction	Number of subjects with adverse drug reaction	3 weeks

Collaborators and Investigators

• Sponsor: University of Malaya
• Collaborators: Ministry of Health, Malaysia
• Investigators: Principal Investigator: Khim Boon Tee, University of Malaya

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2019
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 10, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Actual): December 26, 2019
• Last Update Submitted That Met QC Criteria: December 23, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Healthy volunteers; Metformin; Metabolomics; Phase 1; Herbal Medicine; Pharmacometabolomic; Andrographis paniculata
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Platelet Aggregation Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Metformin; Andrographolide
• Other Study ID Numbers: P1-PKPD-Metabolomic

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions by Medical Research Ethics Committee, University Malaya Medical Centre.
• IPD Sharing Time Frame: The information is available approximately in December 2020 or when the study is published. The data is available for 2 years.
• IPD Sharing Access Criteria: Kindly email to Tee Khim Boon for the above information.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No