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

Primary Purpose

Diabetes Mellitus, Type 2, Hepatitis C, Drug Interactions

Status

Completed

Phase

Phase 1

Locations

Egypt

Study Type

Interventional

Intervention

Metformin

Daclatasvir

About this trial

This is an interventional other trial for Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

Subject is at least 18-55 years at screening.
Subject has a Body Mass Index of 18 to 35 kg/m2.
Subject are non smokers or moderate smokers(not more than 10 cigarettes per day)
Subjects is willing to participate and give their final written consent prior to the commencement of the study procedures
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.
Subject has a normal blood pressure and pulse rate, according to the reference normal ranges.

Exclusion Criteria:

Treatment with any known enzyme-inducing/inhibiting agents prior to the start of the study and throughout the study.
Subjects who have taken any medication two weeks preceding of the trial starting date.
Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.
Gastrointestinal diseases.
Renal diseases.
Cardiovascular diseases specially transient ischemic attacks and cardiac dysrhythmia .
Pancreatic disease including diabetes.
Hepatic diseases as hepatic failure, cirrhosis, galactose intolerance, fructose intolerance, glycogen storage diseases
Hematological disease or pulmonary disease
Abnormal laboratory values.
Subjects who have donated blood or who have been involved in a drug study within 6 weeks preceding the start of the study.
Positive HIV test.
History of or current abuse of drugs, alcohol or solvents.
Endocrine disorders as Pheochromocytoma, Addison disease, glucagon deficiency, carcinomas, extrahepatic tumors
Autoimmune disorders as Graves disease
Central nervous system (CNS) disorders

Sites / Locations

Drug research centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Metformin

Metformin and Daclatasvir

Arm Description

Subjects administered Metformin 500mg(Glucophage tablets) twice daily till day(4) then Metformin 1000mg twice daily till day(7)

Subjects Coadministered Metformin 500mg(Glucophage tablets) twice daily and Daclatasvir 60mg tablets once daily till day (4) then Metformin 1000mg twice daily and Daclatasvir 60mg tablets once daily till Day(7)

Outcomes

Primary Outcome Measures

(AUC0→12)

Area under the plasma concentration-time curve measured in (nanogram(ng).hr/ml)

Area under the plasma concentration-time curve from time 0 to infinity (AUC0→∞)

Area under the plasma concentration-time curve from time 0 to infinity measured in(ng.hr/ml)

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)

Maximum drug concentration in plasma at steady state(Cpss)

Maximum drug concentration in plasma at steady state measured in (ng/ml)

Half life( t½) of drug in plasma

Half life of drug measured in Hours(hr)

Mean residence time of drug(MRT)

Mean residence time of drug in plasma measured in (hr)

steady state Clearance of drug(CLss)

steady state Clearance of drug measured in (ml/min)

Renal Clearance of drug(CLr)

Renal Clearance of drug measured in (ml/min)

Cumulative amount of drug eliminated in urine (Ae)

Cumulative amount of drug eliminated in urine measured in (microgram(ug)/ml)

Maximum excretion rate (Urate max)

Maximum excretion rate for the drug measured in (milligram(mg)/hr)

Secondary Outcome Measures

Blood Glucose(BG) levels

Blood glucose levels measured in (mg/dl)

Area under the BG-time curve(AUG)0-3hr

Area under the BG-time curve measured in (mg.hr/dl)

Maximum Glucose concentration(Gmax)

Maximum Glucose concentration measured in (mg/dl)

Full Information

NCT ID

NCT03686722

First Posted

September 23, 2018

Last Updated

October 10, 2018

Sponsor

Mohamed Raslan

Collaborators

Ain Shams University, Drug Research Centre, Cairo, Egypt

1. Study Identification

Unique Protocol Identification Number

NCT03686722

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

September 9, 2017 (Actual)

Primary Completion Date

October 30, 2017 (Actual)

Study Completion Date

December 6, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mohamed Raslan

Collaborators

Ain Shams University, Drug Research Centre, Cairo, Egypt

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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)

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2, Hepatitis C, Drug Interactions

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Model Description

Twenty Eligible Adult Subjects Will be Randomized Equally into two Groups: A and B To Receive Either: Group (A):10 subjects will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice on day 5-7 Group (B):10 subjects will receive 500 mg co-administered daily with Daclatasvir 60 mg once daily on day 1-4 then 1000mg Metformin co-administered twice daily with Daclatasvir 60 mg once daily on day 5-7

Masking

InvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metformin

Arm Type

Active Comparator

Arm Description

Subjects administered Metformin 500mg(Glucophage tablets) twice daily till day(4) then Metformin 1000mg twice daily till day(7)

Arm Title

Metformin and Daclatasvir

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

Metformin is used primarly in treatment of diabetes type II

Intervention Type

Drug

Intervention Name(s)

Daclatasvir

Intervention Description

Daclatsvir is a direct acting antiviral drug

Primary Outcome Measure Information:

Title

(AUC0→12)

Description

Area under the plasma concentration-time curve measured in (nanogram(ng).hr/ml)

Time Frame

From first sampling interval(time zero) up to 12 hours

Title

Area under the plasma concentration-time curve from time 0 to infinity (AUC0→∞)

Description

Area under the plasma concentration-time curve from time 0 to infinity measured in(ng.hr/ml)

Time Frame

From first sampling interval up to infinity

Title

Area under the plasma concentration-time curve from time 0 to tau(AUC0→tau)

Description

Area under the plasma concentration-time curve from time 0 to tau measured in(ng.hr/ml)

Time Frame

From first sampling interval up to dosing interval(Tau)

Title

Maximum drug concentration in plasma at steady state(Cpss)

Description

Maximum drug concentration in plasma at steady state measured in (ng/ml)

Time Frame

Time corresponding to maximum drug concentration in plasma at steady state

Title

Half life( t½) of drug in plasma

Description

Half life of drug measured in Hours(hr)

Time Frame

Up to 12 hours

Title

Mean residence time of drug(MRT)

Description

Mean residence time of drug in plasma measured in (hr)

Time Frame