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A Drug-drug Interaction Study Between Daclatasvir and Metformin (DATE-3)

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ClinicalTrials.gov Identifier: NCT02565862
Recruitment Status : Completed
First Posted : October 1, 2015
Last Update Posted : April 7, 2016
Sponsor:
Information provided by (Responsible Party):
Radboud University

Brief Summary:
This study aims to provide clinical information on a potential drug-drug interaction between daclatasvir and metformin.

Condition or disease Intervention/treatment Phase
Hepatitis C Diabetes Mellitus Insulin Resistance Drug: Daclatasvir Drug: Metformin Phase 1

Detailed Description:

Daclatasvir is a recently approved anti-HCV agent that is a cytochrome P450 3a (CYP3A) substrate but does not affect CYP3A itself. It is also a moderate inhibitor of various membrane transporters such as organic anion-transporting polypeptide 1B1 (OATP1B1) , p-glycoprotein (P-gP), and organic cation transporter (OCT) 1 and 2.

Metformin is used to treat diabetes mellitus. It is an OCT-2 and OCT-1 substrate and when combined with daclatasvir increased levels of metformin may occur, with risk on hypoglycaemic episodes. The Summary of Product Characteristics (SmPC) of daclatasvir currently does not mention this potential drug-drug interaction.

HCV is associated with insulin resistance (IR) which may develop to diabetes mellitus (DM). The prevalence of IR in HCV infected patients is estimated varying from 30% to 70%. Several studies showed that IR has a negative impact on the achievement of an undetectable HCV viral load after completing 12 weeks of treatment (Sustained Virologic Response (SVR)).

This study aims to provide clinical information on a potential drug-drug interaction between daclatasvir and metformin.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: A Drug-drug Interaction Study Between the Novel Anti-hepatitis c Virus (HCV) Agent Daclatasvir and The Antidiabetic Agent Metformin in Healthy Volunteers
Study Start Date : January 2016
Actual Primary Completion Date : March 2016
Actual Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Active Comparator: Treatment A

Day 1-2: 500mg twice daily (BID) metformin film-coated tablets

Day 3-8: 1000mg BID metformin film-coated tablets

Drug: Metformin
Experimental: Treatment B

Day 15-16: 500mg BID metformin film-coated tablets + 60mg once daily (QD) daclatasvir film-coated tablets

Day 17-22: 1000mg BID metformin film-coated tablets

+ 60mg QD daclatasvir film-coated tablets

Drug: Daclatasvir
Other Name: Daklinza

Drug: Metformin



Primary Outcome Measures :
  1. Area Under the Curve (AUC) [ Time Frame: up to 24 hours after administration for daclatasvir and up to 12 hours after administration for metformin ]

Secondary Outcome Measures :
  1. adverse events [ Time Frame: 4 weeks ]
    adverse events will be collected up to 4 weeks in total (entire study)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Subject is at least 18 and not older than 55 years at screening.
  2. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to Day 1.
  3. Subject has a Quetelet Index (Body Mass Index) of 18 to 35 kg/m2, extremes included.
  4. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
  5. Subject is in good age-appropriate health condition as established by medical history, physical examination, and electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to Day 1. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded.
  6. Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.

Exclusion Criteria:

  1. Creatinine clearance below 60mililiter/minute (ml/min).
  2. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
  3. Positive HIV test.
  4. Positive hepatitis B or C test.
  5. Pregnant female (as confirmed by an Human chorionic gonadotropin (hCG) test performed less than 4 weeks before day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study.
  6. Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen (max 2 gram/day).
  7. Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal and hepatic disorders (increased alanine aminotransferase (ALAT)/ASAT), hormonal disorders (especially diabetes mellitus), coagulation disorders.
  8. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
  9. History of or current abuse of drugs, alcohol or solvents.
  10. Inability to understand the nature and extent of the study and the procedures required.
  11. Participation in a drug study within 60 days prior to Day 1.
  12. Donation of blood within 60 days prior to Day 1.
  13. Febrile illness within 3 days before Day 1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02565862


Locations
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Netherlands
CRCN, Radboud University Medical Center
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
Investigators
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Principal Investigator: David Burger, PharmD, PhD Radboud University

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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT02565862     History of Changes
Other Study ID Numbers: UMCN-AKF 14.11
First Posted: October 1, 2015    Key Record Dates
Last Update Posted: April 7, 2016
Last Verified: April 2016

Keywords provided by Radboud University:
HCV
Diabetes Mellitus
Daclatasvir
Metformin
drug-drug interaction
pharmacokinetics

Additional relevant MeSH terms:
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Diabetes Mellitus
Hepatitis
Hepatitis C
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hyperinsulinism
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs