Phase 1 Study to Evaluate the Safety and Tolerability of DS-1040b IV Infusion With Clopidogrel in Healthy Subjects

NCT02560688 | Completed Phase 1

• 2 other identifiers: DS1040-A-E1062015-003018-26
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to test the hypothesis that coadministration of clopidogrel with DS-1040b will be safe and well tolerated. Subjects entering the study will initially receive a single 12 hour infusion of DS-1040b, to generate data on the effect of DS-1040b alone. After a wash-out period (to ensure that no DS-1040b is left in the blood) subjects will receive repeated clopidogrel doses over 5 days to generate data on the effect of clopidogrel alone. On the sixth day subjects will receive both DS-1040b and clopidogrel, and the effects will be compared to when the two treatments were given alone.

Conditions

Drug Interaction

Keywords

drug interaction; clopidogrel; healthy subjects

Outcome Measures

Primary Outcomes (3)

• number of adverse events

  Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by adverse events,from the time of dosing up to 5 days postdose.

  5 days

• physical exam profile

  Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by physical examination findings, vital signs, 12-lead electrocardiograms (ECGs), clinical safety laboratory tests from the time of dosing up to 5 days postdose.

  5 days

• bleeding time measurements

  Evaluation of the safety and tolerability of DS-1040 administered alone or with clopidogrel, as determined by bleeding time assessments from the time of dosing up to 5 days postdose.

  5 days

Secondary Outcomes (8)

• DS-1040b plasma concentration profile Time of Maximum plasma concentration(Tmax)

  5 days

• DS-1040b plasma concentration profile Area Under the plasma concentration time Curve (AUC)

  5 days

• DS-1040b plasma concentration profile Maximum plasma concentration (Cmax)

  5 days

• changes in pharmacodynamic profile single administration

  5 days

• clopidogrel plasma concentration profile Tmax

  5 days

Study Arms (3)

Period 1 - DS-1040b

EXPERIMENTAL

Single 12-hour intravenous infusion of DS-1040b (20 mg)

Drug: DS-1040b

Period 2 - Clopidogrel

OTHER

Clopidogrel (Plavix) administered orally over 5 days (300 mg loading dose on Day 1 followed by 75 mg daily on Days 2-5)

Drug: Clopidogrel

Period 2 - DS-1040b and Clopidogrel

EXPERIMENTAL

Concomitant administration of DS-1040b (20 mg single 12-hour intravenous infusion) and clopidogrel (single 75 mg oral dose)

Drug: DS-1040b; Drug: Clopidogrel

Interventions

DS-1040b DRUG

20 mg single 12-hour intravenous infusion

Period 1 - DS-1040b; Period 2 - DS-1040b and Clopidogrel

Clopidogrel DRUG

Clopidogrel (Plavix) administered orally 300 mg loading dose on Day 1 followed by 75 mg daily on Days 2-5

Also known as: Plavix

Period 2 - Clopidogrel; Period 2 - DS-1040b and Clopidogrel

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects of non-childbearing potential; subjects must be aged 18 years to 60 years, inclusive.
• Subjects with a body mass index (BMI) of 18 kg/m2 to 30 kg/m2, inclusive, and weighing between 50 kg and 100 kg, inclusive. BMI is calculated as weight \[kg\]/(height \[m\])\*2.
• Subjects must be in good health as determined by medical history, physical examination and Screening investigations, and taking no regular medication.
• Female subjects must be of non-childbearing potential as follows:
• Must be postmenopausal (the last menstrual period was at least 12 months before Screening, and a follicle-stimulating hormone \[FSH\] test at Screening confirms postmenopausal status); or
• Must be surgically sterile having undergone hysterectomy, bilateral oophorectomy, bilateral salpingectomy and/or bilateral tubal ligation.
• Willing to comply with all study restrictions, including the use of contraception, concomitant medication and dietary and lifestyle restrictions.
• Possessing sufficient intelligence to understand the nature of the study and any hazards of participating in it, and the ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire study.
• Has given written consent to participate after reading the informed consent form (ICF), and after having the opportunity to discuss the study with the Investigator or his/her delegate.
• Have given written consent to have his/her data entered into The Overvolunteering Prevention System.

You may not qualify if:

• Clinically relevant abnormal history, physical findings, ECG findings or laboratory values that could interfere with the objectives of the study or the safety of the subject.
• Presence or history of acute or chronic illness, including (but not limited to) liver or kidney disease, hypertension, seizures, or any known impairment of endocrine, or other specific body-organ dysfunction.
• Presence or history of severe adverse reaction to any medicine.
• Presence or history of malignant disease.
• Surgery (eg, stomach bypass) or medical condition that might affect absorption of medicines.
• Significant illness within 4 weeks before the dose of study medication.
• Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months, or unwilling to abstain from participating in other clinical trials during the study and for 3 months after receipt of study medication.
• Participation in another clinical study with DS-1040b.
• Day-1 bleeding time greater than 10 minutes.
• Blood pressure (BP) and heart rate (HR) in semi-supine position at the Screening examination outside the ranges 90 to 140 mmHg systolic, 40 to 90 mmHg diastolic; HR 40 to 100 beats/min. A subject with vital signs outside the reference range for the population being studied may be included at the Investigator's discretion if it is unlikely to introduce additional risk factors and will not interfere with study procedures.
• Abnormal electrocardiogram ECG waveform morphology at Screening that would preclude accurate measurement of the uncorrected QT interval (QT) duration.
• QT interval for HR corrected using Fridericia's formula (QTcF) interval duration \> 430 msec for men or \> 450 msec for women, obtained as an average from the measurements on triplicate Screening ECGs.
• Use of any prescription medicine, over-the-counter (OTC) medications, herbal remedies (such as St John's Wort), or food known to be strong inhibitors or strong inducers of CYP enzymes during the 30 days before the dose of study medication; use of any other prescription or OTC medicine (except as permitted, including dietary supplements or herbal remedies, during the 7 days before the first dose of study medication.
• Consumption of certain foods or beverages before the dose and throughout the study period.
• Loss of more than 400 mL blood plasma, platelets or any other blood components during the 3 months before the first dose of study medication, or unwilling to abstain from doing so during the study and for 3 months after receipt of study medication.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (1)

Hammersmith Medicines Research

London, NW10 7EW, United Kingdom

Location

Related Publications (1)

• Limsakun T, Dishy V, Mendell J, Pizzagalli F, Pav J, Kochan J, Vandell AG, Rambaran C, Kobayashi F, Orihashi Y, Warren V, McPhillips P, Zhou J. Safety and Pharmacokinetics of DS-1040 Drug-Drug Interactions With Aspirin, Clopidogrel, and Enoxaparin. J Clin Pharmacol. 2020 Jun;60(6):691-701. doi: 10.1002/jcph.1568. Epub 2020 Feb 27.

  PMID: 32106339 DERIVED

MeSH Terms

Interventions

Clopidogrel

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2015
• First Posted: September 25, 2015
• Study Start: December 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: December 24, 2018

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

GB (1)