Clinical trial NCT04161404: Pharmacometabolomics of Andrographis Paniculata And Metformin In Healthy Volunteers Under Fasting Condition
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Pharmacokinetics
Molecular Mechanisms of Pharmacological Action
Keywords: Pharmacometabolomic
Metformin
Andrographis paniculata
Metabolomics
Phase 1
Healthy volunteers
Herbal Medicine
Lead sponsor: University of Malaya
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Malaysia
First posted: 2019-11-13
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Open label, block-randomized, three-period, crossover, single dose oral administration of investigational products. Subjects will undergo at least 7 days washout period.
Primary purpose: OTHER

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area under the plasma concentration-time curve (AUC) of Andrographis paniculata
timeFrame: 0-24 hours
measure: Cmax of Andrographis paniculata
timeFrame: 0-24 hours
measure: Tmax of Andrographis paniculata
timeFrame: 0-24 hours
measure: Area under the plasma concentration-time curve (AUC) of Metformin
timeFrame: 0-24 hours
measure: Cmax of Metformin
timeFrame: 0-24 hours
measure: Tmax of Metformin
timeFrame: 0-24 hours
Secondary outcomes:
measure: Metabolic pathway of Andrographis paniculata
timeFrame: 24 hours
measure: Metabolic pathway of Metformin
timeFrame: 24 hours
measure: Adverse drug reaction
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: Clinical Investigation Centre, University Malaya Medical Centre
state: Wilayah Persekutuan Kuala Lumpur
Study officials:
affiliation: University of Malaya
name: Khim Boon Tee
role: PRINCIPAL_INVESTIGATOR
References: