A Drug-drug Interaction Study Between Daclatasvir and Metformin

NCT02565862 | Completed Phase 1

• 1 other identifier: UMCN-AKF 14.11
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hepatitis C; Diabetes Mellitus; Insulin Resistance

Keywords

HCV; Diabetes Mellitus; Daclatasvir; Metformin; drug-drug interaction; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC)

  up to 24 hours after administration for daclatasvir and up to 12 hours after administration for metformin

Secondary Outcomes (1)

• adverse events

  4 weeks

Study Arms (2)

Treatment A

ACTIVE COMPARATOR

Day 1-2: 500mg twice daily (BID) metformin film-coated tablets Day 3-8: 1000mg BID metformin film-coated tablets

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

Drug: Daclatasvir; Drug: Metformin

Interventions

Daclatasvir DRUG

Also known as: Daklinza

Treatment B

Metformin DRUG

Treatment A; Treatment B

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

CRCN, Radboud University Medical Center

Nijmegen, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 28474741 RESULT

MeSH Terms

Conditions

Hepatitis C; Diabetes Mellitus; Insulin Resistance

Interventions

daclatasvir; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• David Burger, PharmD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 1, 2015
• Study Start: January 1, 2016
• Primary Completion: March 1, 2016
• Study Completion: April 1, 2016
• Last Updated: December 7, 2020

Record last verified: 2020-12

Locations

NL (1)