DS1040b/Aspirin Drug/Drug Interaction Study

NCT02071004 | Completed Phase 1

• 1 other identifier: DS1040-A-E102
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open label, single dose study, after 5 days of aspirin treatment, in healthy male and female subjects. It is hypothesized that co-administering DS-1040b with aspirin at steady state will be safe and well tolerated by healthy male and female subjects.

Conditions

Acute Ischemic Stroke

Keywords

acute ischemic stroke

Outcome Measures

Primary Outcomes (1)

• bleeding time

  To assess the safety (including bleeding time) and tolerability of a single IV dose of DS-1040b following 5 days aspirin treatment in healthy subjects

  day 0 to day 5 after dosing

Secondary Outcomes (5)

• change in D-dimer level

  day 0 - day 5 after dosing

• Cmax

  Days 5, 6, and 7 after dosing

• Tmax

  Days 5, 6, and 7 after dosing

• AUC

  Days 5, 6, and 7 after dosing

• half-life

  Days 5, 6, and 7 after dosing

Study Arms (2)

Aspirin

OTHER

Dispersible tablet, 300mg \& 75 mg, once daily for 5 days

Drug: Aspirin

DS-1040b

EXPERIMENTAL

IV of 6 mg given once over 30 minutes

Drug: DS-1040b

Interventions

DS-1040b DRUG

IV of 6 mg given once over 30 minutes

DS-1040b

Aspirin DRUG

Dispersible tablet, 300mg \& 75 mg, once daily for 5 days

Aspirin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects, aged 18 to 45 years.
• A body mass index (BMI, or Quetlet index) in the range of 18.0 to 30.0 kg/m2, and weighing between 50 and 100 kg at screening.
• Male subjects have to agree to contraception (condom with spermicide) in addition to having their female partner (if of child-bearing potential) use another form of contraception (e.g., an intrauterine device, diaphragm with spermicide, oral contraceptive, injectable, or sub dermal hormonal implant) from the first dose until 16 weeks following the last dose administration. Also, the male subjects must not donate sperm after the study for a period of four months.
• All women must have a negative serum pregnancy test at screening and a negative urine pregnancy test at admission (Day -1). Women must be of non-childbearing potential either: Surgically sterile (i.e., bilateral tubal ligation or removal of both ovaries and/or uterus at least 6 months prior to dosing) or naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to dosing, with a follicle stimulating hormone (FSH) level at screening of ≥ 40 mIU/mL.
• Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire trial.
• Willingness to give written consent to participate after reading the ICF, and after having the opportunity to discuss the trial with the Investigator or his delegate.
• Willingness to give written consent to have data entered into The Overvolunteering Prevention Scheme.
• Willing to abstain from grapefruit/grapefruit juice and Seville oranges from 7 days before the first dose and throughout the study.
• Willing to refrain from consuming food or beverages containing caffeine/xanthine starting 24 hours prior to check-in on Day -1.

You may not qualify if:

• Clinically relevant abnormal history, including cardiovascular, haematologic, pulmonary, hepatic, renal, gastrointestinal, connective tissue disease, uncontrolled endocrine/metabolic, oncologic (within the last 5 years), neurologic (including previous transient ischemic attack or stroke), and psychiatric diseases, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
• History of a serious reaction to any medicine.
• History of major bleeding, stomach ulcer, Raynaud's disease, major trauma, or major surgical procedure of any type within 6 months of dosing.
• History of minor bleeding episodes such as epistaxis, rectal bleeding (spots of blood on toilet paper), and gingival bleeding within 3 months before the study treatment.
• Familial or documented or suspected coagulopathy and haemoglobinopathy.
• Females with a history of dysfunctional uterine bleeding, including history of menorrhagia, metrorrhagia, or polymenorrhea.
• History of an operation (e.g. stomach bypass), or a condition that could affect how the body handles or absorbs medicines.
• History of gastro-oesophageal reflux disease.
• Females who are breastfeeding.
• Positive urine or faecal occult blood test at screening or admission (Day -1 or day 1).
• Bleeding time \> 9.5 minutes at screening).
• aPTT, PT, INR, or platelet count outside the limit of normal of the clinical laboratory's reference range at screening.
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2 (based on Modification of Diet in Renal Disease \[MDRD\] equation).
• Positive test for hepatitis B, hepatitis C, HIV1 \& HIV2.
• QTcF interval duration \> 430 msec for males and 450 msec for females, obtained as an average from the 3 ECG measurements on the triplicate screening ECGs.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (1)

Hammersmith Medicines Research Ltd.

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

Conditions

Ischemic Stroke

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

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: February 21, 2014
• First Posted: February 25, 2014
• Study Start: January 1, 2014
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: December 24, 2018

Record last verified: 2014-02

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)