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

NCT03686722 | Completed Phase 1

• 1 other identifier: MET-DAC\DDIS\01217
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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)

Conditions

Diabetes Mellitus, Type 2; Hepatitis C; Drug Interactions

Outcome Measures

Primary Outcomes (10)

• (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

• 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)

  From first sampling interval up to infinity

• 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)

• 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

• Half life( t½) of drug in plasma

  Half life of drug measured in Hours(hr)

  Up to 12 hours

• Mean residence time of drug(MRT)

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

  From first sampling interval up to 12 hours

• steady state Clearance of drug(CLss)

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

  From first sampling interval up to 12 hours

• Renal Clearance of drug(CLr)

  Renal Clearance of drug measured in (ml/min)

  From first sampling interval up to 12 hours

• 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

• 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 Outcomes (3)

• Blood Glucose(BG) levels

  up to 3 hours

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

  up to 3 hours

• Maximum Glucose concentration(Gmax)

  up to 3 hours

Study Arms (2)

Metformin

ACTIVE COMPARATOR

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

Drug: Metformin

Metformin and Daclatasvir

EXPERIMENTAL

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)

Drug: Metformin; Drug: Daclatasvir

Interventions

Metformin DRUG

Metformin is used primarly in treatment of diabetes type II

Metformin; Metformin and Daclatasvir

Daclatasvir DRUG

Daclatsvir is a direct acting antiviral drug

Metformin and Daclatasvir

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mohamed Raslan: lead
• Ain Shams University: collaborator
• Drug Research Centre, Cairo, Egypt: collaborator

Study Sites (1)

Drug research centre

Cairo, Egypt

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hepatitis C

Interventions

Metformin; daclatasvir

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Mohamed Raslan

  Ainshams university

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: September 23, 2018
• First Posted: September 27, 2018
• Study Start: September 9, 2017
• Primary Completion: October 30, 2017
• Study Completion: December 6, 2017
• Last Updated: October 12, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)