A Drug-drug Interaction Study Between Daclatasvir and Metformin

NCT ID: NCT02565862

Last Updated: 2020-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2016-04-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Hepatitis C Diabetes Mellitus Insulin Resistance

Keywords

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HCV Diabetes Mellitus Daclatasvir Metformin drug-drug interaction pharmacokinetics

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Treatment A

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

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

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

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

Group Type EXPERIMENTAL

Daclatasvir

Intervention Type DRUG

Metformin

Intervention Type DRUG

Interventions

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Daclatasvir

Intervention Type DRUG

Metformin

Intervention Type DRUG

Other Intervention Names

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Daklinza

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Burger, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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CRCN, Radboud University Medical Center

Nijmegen, , Netherlands

Site Status

Countries

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Netherlands

References

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Smolders EJ, Colbers A, de Kanter CTMM, Velthoven-Graafland K, Wolberink LT, van Ewijk-Beneken Kolmer N, Drenth JPH, Aarnoutse RE, Tack CJ, Burger DM. Metformin and daclatasvir: absence of a pharmacokinetic-pharmacodynamic drug interaction in healthy volunteers. Br J Clin Pharmacol. 2017 Oct;83(10):2225-2234. doi: 10.1111/bcp.13323. Epub 2017 Jun 6.

Reference Type RESULT
PMID: 28474741 (View on PubMed)

Other Identifiers

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UMCN-AKF 14.11

Identifier Type: -

Identifier Source: org_study_id