Clinical trial: DS1040b/Aspirin Drug/Drug Interaction Study (NCT02071004)

Eligibility criteria:
Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.

          -  Abnormal waveform morphology on any of the ECGs at screening at admission that would
             preclude accurate measurement of the QT interval duration.

          -  Physical trauma, dental extraction, surgery, or a significant illness within 4 weeks
             before the first dose.

          -  History or presence of keloid, hyperpigmentation, or other adverse reaction to skin
             injury or surgery.

          -  Use of any prescribed or non-prescribed (over-the-counter [OTC]) systemic medications
             (including anticoagulants or antiplatelet medications), topical medications, or herbal
             supplements within 14 days before the first dose (excluding paracetamol ≤ 2 g/day).
             St. John's Wort (hypericin) must not have been taken for at least 30 days before the
             first dose.

          -  Donated or lost > 400 mL of blood or plasma during 3 months before the first dose on
             Day 1.

          -  Donation of blood, plasma, platelets, or any other blood components during the 3
             months before the trial, or unwilling to abstain from doing so during the study and
             for 3 months after receipt of trial medication.

          -  Participated in a clinical study involving administration of an investigational drug,
             or a marketed drug within 90 days before administration of the first dose.

          -  Male subjects who consume more than 21 units of alcohol per week or female subjects
             who consume more than 14 units of alcohol per week (1 unit of alcohol equals 1/2 pint
             of beer, a glass of wine, or 1 measure of spirits) or those subjects who have a
             significant history of alcoholism or drug/chemical abuse within the last 2 years.

          -  Use of tobacco products or nicotine-containing products within 3 months before the
             first dose.

          -  Positive results on tests for drugs of abuse, carbon monoxide, or alcohol at screening
             or admission.

          -  Possibility that the volunteer will not cooperate with the requirements of the
             protocol.

          -  Objection by General Practitioner (GP) to volunteer entering the trial.

          -  Known aspirin allergy or intolerance.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 45 Years

Patient description (medical language): A 23-year-old woman comes to the emergency department with a history of nosebleeds lasting for 1 hour. She has a history of heavy menses as well as occasional gum bleeding following dental procedures. Her mother also has a history of menorrhagia. Laboratory tests reveal increased bleeding time and slightly increased partial thromboplastin time. She has no other medical conditions and is otherwise healthy. Her coagulation study shows CB = 0.30 IU/mL and FVIII:C = 0.37 IU/mL. She is not smoking or using any kind of illicit drugs. She uses alcohol occasionally and is in ra elationship with her boyfriend for the past 2 years.

Patient description (patient's own words): I had to rush to the ER because of a non-stop nosebleed that had been on for 1 hour. As a 23-year-old, I always had heavy periods, and sometimes, my gums would bleed after going to the dentist or brushing my teeth. I thought that it was not very alarming since my mom also had heavy periods. I did some lab tests that showed that I had increased bleeding time and long clotting time. Otherwise, I'm pretty healthy, and I don't smoke or take any kind of drugs. I drink only at parties from time to time. I have been with my boyfriend for the last 2 years. I did a coagulation study and I got the following results: CB = 0.30 IU/mL and FVIII:C = 0.37 IU/mL.

Does the patient match the trial criteria? Contradiction