Hepatitis CPhase 1DATE-3NCT02565862
A Drug-drug Interaction Study Between Daclatasvir and Metformin
A Phase 1 study testing Daclatasvir and Metformin in people with Hepatitis C and Diabetes Mellitus, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
This study aims to provide clinical information on a potential drug-drug interaction between daclatasvir and metformin. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C, Diabetes Mellitus, Insulin Resistance
- What is being tested?
- Daclatasvir and Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2016to Apr 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subject is at least 18 and not older than 55 years at screening.
- Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to Day 1.
- Subject has a Quetelet Index (Body Mass Index) of 18 to 35 kg/m2, extremes included.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- 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.
- Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.
Who cannot join
- Creatinine clearance below 60mililiter/minute (ml/min).
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Positive HIV test.
- Positive hepatitis B or C test.
- 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.
- Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen (max 2 gram/day).
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- 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.
- Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- History of or current abuse of drugs, alcohol or solvents.
- Inability to understand the nature and extent of the study and the procedures required.
- Participation in a drug study within 60 days prior to Day 1.
- Donation of blood within 60 days prior to Day 1.
- Febrile illness within 3 days before Day 1.
Trial locations and contacts
1 site in 1 country.
About this study
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
This study aims to provide clinical information on a potential drug-drug interaction between daclatasvir and metformin.
Read the 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.
- Conditions
- Hepatitis C, Diabetes Mellitus, Insulin Resistance
- Being tested
- Daclatasvir, Metformin
- Keywords
- HCV, Diabetes Mellitus, Daclatasvir, Metformin, drug-drug interaction, pharmacokinetics
- Medical subject headings
- Hepatitis C, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclatasvirDrug
Also called Daklinza
MetforminDrug
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Active comparator | Day 1-2: 500mg twice daily (BID) metformin film-coated tablets
Day 3-8: 1000mg BID metformin film-coated tablets Receives: Drug: Metformin |
| Treatment B | Experimental | 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 Receives: Drug: Daclatasvir; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve (AUC)
Measured: up to 24 hours after administration for daclatasvir and up to 12 hours after administration for metformin
Secondary outcomes (1)
adverse events
adverse events will be collected up to 4 weeks in total (entire study)
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2015 (estimated)
- Study startJan 2016
- Primary completionMar 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Burger, PharmD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02565862
- Sponsor's protocol ID
- UMCN-AKF 14.11
- Acronym
- DATE-3
- Status last verified
- Dec 2020
- First submitted
- 30 Sep 2015
- Last updated
- 7 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 28474741
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02565862
- Acronym / sponsor ID
- DATE-3 / UMCN-AKF 14.11
- Conditions
- Hepatitis C, Diabetes Mellitus, Insulin Resistance
- Keywords
- HCV, Diabetes Mellitus, Daclatasvir, Metformin, drug-drug interaction, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Mar 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 1 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to provide clinical information on a potential drug-drug interaction between daclatasvir and metformin.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Active comparator | Drug: MetforminDay 1-2: 500mg twice daily (BID) metformin film-coated tablets Day 3-8: 1000mg BID metformin film-coated tablets |
| Treatment B | Experimental | Drug: Daclatasvir, Drug: MetforminDay 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 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Subject is at least 18 and not older than 55 years at screening.
- Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to Day 1.
- Subject has a Quetelet Index (Body Mass Index) of 18 to 35 kg/m2, extremes included.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- 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.
Key exclusion criteria (13 listed)
- Creatinine clearance below 60mililiter/minute (ml/min).
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Positive HIV test.
- Positive hepatitis B or C test.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaclatasvirAlso: Daklinza | Drug | Treatment B |
| Metformin | Drug | Treatment A, Treatment B |
Primary outcome
Area Under the Curve (AUC)
Time frame: up to 24 hours after administration for daclatasvir and up to 12 hours after administration for metformin
1 secondary outcome
adverse events
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
- Results publication: PubMed 28474741Smolders 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Burger, PharmD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Daclatasvir and Metformin in people with Hepatitis C and Diabetes Mellitus, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve (AUC) (time frame: up to 24 hours after administration for daclatasvir and up to 12 hours after administration for metformin). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02565862, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2020.