Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetis and Pharmacodynamics of Metformin

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetics and Pharmacodynamics of Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03686722
• Other study ID #: MET-DAC\DDIS\01217
• Status: Completed
• Phase: Phase 1
• Start date: September 9, 2017
• Est. completion date: December 6, 2017

Study information

• Verified date: October 2018
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Randomized,Two-period, Crossover Study to Determine the Possibility of Drug-drug Interaction After Co-administration of Metformin and Daclatasvir Where Twenty Eligible Adult Subjects Will be Randomized to Receive Either Metformin Only and/or Metformin Co-administered With Daclatasvir to measure primary outcomes including pharmacokinetics parameters as: Maximum drug concentration in plasma(Cmax), Area under the Plasma concentration Versus Time Curve from time 0 to 12 hours(AUC0-12), Clearance(CL)

Description:

Study Design:

A randomized, one-way, single blinded, two-period, crossover study in adult human healthy egyptian volunteers

Methodology:

period (I): Group A:10 volunteers will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice on day 5-7

GroupB:10 volunteers will receive 500 mg Metformin twice daily + Daclatasvir (DCV) 60 mg once daily on day 1-4 then 1000mg metformin twice daily+DCV 60 mg once daily on day 5-7

period (II): Group A:10 volunteers will receive 500 mg Metformin twice daily + Daclatasvir (DCV) 60 mg once daily on day 1-4 then 1000mg metformin twice daily+DCV 60 mg once daily on day 5-7

Group B:10 volunteers will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice daily on day 5-7

All drug administration will be followed by 240 ml of water after at least 10 hours fasting prior to administration.

The two treatment periods will be separated by a one week washout period

Blood Sampling will be collected at a pre-dosing and at 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12 hours Urine samples will be collected for metformin analysis from 0 to 12 hours after drug administration.

A 75 g Oral glucose tolerance test(OGTT) will be carried out by ingestion of 75g glucose in 240ml water 2-hours post dosing and blood samples for determining glucose concentration during OGTTs were collected immediately before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, and 3 hours after glucose ingestion.

Blood samples will be collected from each volunteer prior to drug administration (blank) at the predetermined sampling intervals after drug administration in ethylene diamine tetra-acetic acid(kEDTA) containing tubes.

These samples will be centrifuged and the plasma harvested and stored at −80°C until assay.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 6, 2017
• Est. primary completion date: October 30, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Subject is at least 18-55 years at screening.

2. Subject has a Body Mass Index of 18 to 35 kg/m2.

3. Subject are non smokers or moderate smokers(not more than 10 cigarettes per day)

4. Subjects is willing to participate and give their final written consent prior to the commencement of the study procedures

5. Subject is in good age-appropriate health condition as established by medical history, physical examination, and results of biochemistry, hematology and urine analysis testing within 4 weeks prior to study.

6. Subject has a normal blood pressure and pulse rate, according to the reference normal ranges.

Exclusion Criteria:

1. Treatment with any known enzyme-inducing/inhibiting agents prior to the start of the study and throughout the study.

2. Subjects who have taken any medication two weeks preceding of the trial starting date.

3. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.

4. Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.

5. Gastrointestinal diseases.

6. Renal diseases.

7. Cardiovascular diseases specially transient ischemic attacks and cardiac dysrhythmia .

8. Pancreatic disease including diabetes.

9. Hepatic diseases as hepatic failure, cirrhosis, galactose intolerance, fructose intolerance, glycogen storage diseases

10. Hematological disease or pulmonary disease

11. Abnormal laboratory values.

12. Subjects who have donated blood or who have been involved in a drug study within 6 weeks preceding the start of the study.

13. Positive HIV test.

14. History of or current abuse of drugs, alcohol or solvents.

15. Endocrine disorders as Pheochromocytoma, Addison disease, glucagon deficiency, carcinomas, extrahepatic tumors

16. Autoimmune disorders as Graves disease

17. Central nervous system (CNS) disorders

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Drug Interactions
• Hepatitis C

Intervention

Drug:
• Metformin
Metformin is used primarly in treatment of diabetes type II
• Daclatasvir
Daclatsvir is a direct acting antiviral drug

Locations

Country	Name	City	State
Egypt	Drug research centre	Cairo

Sponsors (3)

Lead Sponsor	Collaborator
Mohamed Raslan	Ain Shams University, Drug Research Centre, Cairo, Egypt

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	(AUC0?12)	Area under the plasma concentration-time curve measured in (nanogram(ng).hr/ml)	From first sampling interval(time zero) up to 12 hours
Primary	Area under the plasma concentration-time curve from time 0 to infinity (AUC0?8)	Area under the plasma concentration-time curve from time 0 to infinity measured in(ng.hr/ml)	From first sampling interval up to infinity
Primary	Area under the plasma concentration-time curve from time 0 to tau(AUC0?tau)	Area under the plasma concentration-time curve from time 0 to tau measured in(ng.hr/ml)	From first sampling interval up to dosing interval(Tau)
Primary	Maximum drug concentration in plasma at steady state(Cpss)	Maximum drug concentration in plasma at steady state measured in (ng/ml)	Time corresponding to maximum drug concentration in plasma at steady state
Primary	Half life( t½) of drug in plasma	Half life of drug measured in Hours(hr)	Up to 12 hours
Primary	Mean residence time of drug(MRT)	Mean residence time of drug in plasma measured in (hr)	From first sampling interval up to 12 hours
Primary	steady state Clearance of drug(CLss)	steady state Clearance of drug measured in (ml/min)	From first sampling interval up to 12 hours
Primary	Renal Clearance of drug(CLr)	Renal Clearance of drug measured in (ml/min)	From first sampling interval up to 12 hours
Primary	Cumulative amount of drug eliminated in urine (Ae)	Cumulative amount of drug eliminated in urine measured in (microgram(ug)/ml)	From first sampling interval up to 12 hours
Primary	Maximum excretion rate (Urate max)	Maximum excretion rate for the drug measured in (milligram(mg)/hr)	From first sampling interval up to 12 hours
Secondary	Blood Glucose(BG) levels	Blood glucose levels measured in (mg/dl)	up to 3 hours
Secondary	Area under the BG-time curve(AUG)0-3hr	Area under the BG-time curve measured in (mg.hr/dl)	up to 3 hours
Secondary	Maximum Glucose concentration(Gmax)	Maximum Glucose concentration measured in (mg/dl)	up to 3 hours