Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetis and Pharmacodynamics of Metformin
- Conditions
- Diabetes Mellitus, Type 2Hepatitis CDrug Interactions
- Interventions
- Registration Number
- NCT03686722
- Lead Sponsor
- Mohamed Raslan
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 20
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Metformin and Daclatasvir Daclatasvir 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) Metformin Metformin Subjects administered Metformin 500mg(Glucophage tablets) twice daily till day(4) then Metformin 1000mg twice daily till day(7) Metformin and Daclatasvir Metformin 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)
- Primary Outcome Measures
Name Time Method (AUC0→12) From first sampling interval(time zero) up to 12 hours 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→∞) From first sampling interval up to infinity 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) From first sampling interval up to dosing interval(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) Time corresponding to maximum drug concentration in plasma at steady state Maximum drug concentration in plasma at steady state measured in (ng/ml)
Half life( t½) of drug in plasma Up to 12 hours Half life of drug measured in Hours(hr)
Mean residence time of drug(MRT) From first sampling interval up to 12 hours Mean residence time of drug in plasma measured in (hr)
steady state Clearance of drug(CLss) From first sampling interval up to 12 hours steady state Clearance of drug measured in (ml/min)
Renal Clearance of drug(CLr) From first sampling interval up to 12 hours Renal Clearance of drug measured in (ml/min)
Cumulative amount of drug eliminated in urine (Ae) From first sampling interval up to 12 hours Cumulative amount of drug eliminated in urine measured in (microgram(ug)/ml)
Maximum excretion rate (Urate max) From first sampling interval up to 12 hours Maximum excretion rate for the drug measured in (milligram(mg)/hr)
- Secondary Outcome Measures
Name Time Method Blood Glucose(BG) levels up to 3 hours Blood glucose levels measured in (mg/dl)
Area under the BG-time curve(AUG)0-3hr up to 3 hours Area under the BG-time curve measured in (mg.hr/dl)
Maximum Glucose concentration(Gmax) up to 3 hours Maximum Glucose concentration measured in (mg/dl)
Trial Locations
- Locations (1)
Drug research centre
🇪🇬Cairo, Egypt