Clinical trial: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of GSK2330811 in Healthy Subjects (NCT02386436)

Eligibility criteria:
Inclusion Criteria:

          -  Between 18 and 65 years of age inclusive, at the time of signing the informed consent.

          -  Healthy as determined by the investigator or medically qualified designee based on a
             medical evaluation including medical history, physical examination, laboratory tests,
             vital signs and a 12-lead ECG.

          -  A subject with a clinical abnormality or laboratory parameter(s) which is/are not
             specifically listed in the inclusion or exclusion criteria, outside the reference
             range for the population being studied may be included only if the investigator
             documents that the finding is unlikely to introduce additional risk factors and will
             not interfere with the study procedures.

          -  Cohorts 1-4: Body weight <=100 kg and body mass index (BMI) within the range 18.5 -
             29.9 kilogram per meter square (kg/m^2) (inclusive); Cohort 5: Body weight <=80 kg and
             BMI within the range 18.5 - 29.9 kg/m^2 (inclusive).

          -  Female subjects are eligible to participate if not pregnant (as confirmed by a
             negative serum [screening] and urine [Day -1] human chorionic gonadotrophin [hCG]
             test), not lactating, and at least one of the following conditions applies:

          -  Pre-menopausal females with one of the following: Documented tubal ligation,
             Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of
             bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy.

          -  Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a
             blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels
             consistent with menopause). Females on hormone replacement therapy (HRT) and whose
             menopausal status is in doubt will be required to use one of the highly effective
             contraception methods if they wish to continue their HRT during the study. Otherwise,
             they must discontinue HRT to allow confirmation of post-menopausal status prior to
             study enrolment.

          -  Male subjects with female partners of child bearing potential must comply with the
             following contraception requirements from the time of first dose of study medication
             until 15 weeks after dosing of study medication:

          -  Vasectomy with documentation of azoospermia.

          -  Male condom plus partner use of one of the contraceptive options as follows:
             Contraceptive subdermal implant that meets the Standard Operating Procedure (SOP)
             effectiveness criteria including a <1% rate of failure per year, as stated in the
             product label; Intrauterine device or intrauterine system that meets the SOP
             effectiveness criteria including a <1% rate of failure per year, as stated in the
             product label; Oral Contraceptive, either combined or progestogen alone injectable
             progestogen; Contraceptive vaginal ring; percutaneous contraceptive patches. These
             allowed methods of contraception are only effective when used consistently, correctly
             and in accordance with the product label. The investigator is responsible for ensuring
             that subjects understand how to properly use these methods of contraception.

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the consent form and in this protocol.

        Exclusion Criteria:

          -  Subjects with any values for alanine aminotransferase (ALT), aspartate
             aminotransferase (AST), or creatinine that are above the upper limit of normal (ULN);
             any values for platelets or haemoglobin that are below the lower limit of normal
             (LLN); or any out of normal range values for white blood cells (WBC), reticulocytes,
             serum sodium, or serum potassium.

          -  Any history of gastreointestinal bleeding disorders such as peptic ulcer disease,
             haematemesis or other gastrointestinal bleeding.

          -  Subjects with medical conditions associated with increased risk of complications from
             bleeding.

          -  A history of haematological disease, such as anaemia, or acquired platelet disorders
             and coagulation disorders, including drug-induced thrombocytopaenia, idiopathic
             thrombocytopaenia or von Willebrand's disease.

          -  Donation of blood in excess of 500 mL within a 56 day period prior to dosing.

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  Clinically significant findings on ECG.

          -  QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450 milliseconds
             (msec).

          -  History of Tuberculosis (TB) or a positive QuantiFERON®-TB Gold (trademark of Quiagen)
             test at screening: If the QuantiFERON®-TB Gold test is indeterminate, it can be
             repeated once; there must be no other clinical evidence of TB on physical examination
             of the subject.

          -  A history of carcinoma in situ and malignant disease, with the exception of basal cell
             carcinoma that has been completely excised prior to the study.

          -  Subject is unable to abstain from the use of medications known to affect platelet or
             clotting function, including aspirin and other nonsteroidal anti-inflammatory
             drugs(NSAIDs), from within five half-lives of the last dose of the platelet affecting
             medication prior to study day 1, until the end of study follow-up.

          -  History of regular alcohol consumption within 6 months of the study defined as an
             average weekly intake of >21 units for males or >14 units for females. One unit is
             equivalent to 8 grams of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of
             wine or 1 (25 mL) measure of spirits.

          -  Smokers who would not be able to refrain from smoking whilst in the phase I unit.

          -  History of sensitivity to any components of the study medication, or a history of drug
             or other allergy that, in the opinion of the investigator or Medical Monitor,
             contraindicates their participation.

          -  History of severe drug allergies, including type I hypersensitivity reaction to
             parenteral administration of contrast agents, human or murine proteins or monoclonal
             antibodies.

          -  History of opportunistic infections within 1 year of screening or recurrent
             infections, as determined by the investigator.

          -  History of serious infection that resulted in intravenous antibiotics and/or
             hospitalisation within the 6 months prior to screening.

          -  Active bacterial infection, viral infection, or fever >38 degree centigrade within 14
             days prior to Day 1.

          -  A history of frequent reactivation of herpes simplex.

          -  Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test
             result at screening or within 3 months prior to dosing study treatment.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for human immunodeficiency virus (HIV) antibody at screening.

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

          -  Exposure to more than four new chemical or four new biological entities within 12
             months prior to the first dosing day.

          -  Subject is unable to abstain from travelling to regions of high endemic infection, as
             determined by the investigator, for the duration of the study.

          -  Subject is unable to abstain from being immunised with live-attenuated vaccines for 4
             weeks prior to day 1, until the end of follow up.

          -  Subject is unable to refrain from taking prescription or non-prescription drugs
             (including vitamins and dietary or herbal supplements), within 7 days prior to the
             first dose of study medication until completion of the follow-up visit, unless in the
             opinion of the Investigator and sponsor the medication will not interfere with the
             study.

          -  For cohorts including suction blisters (Cohorts 3-5 only): Presence of skin
             abnormalities that would either interfere with study procedures (for example; tattoos,
             naevi, sun burn/sun bed use within 7 days) or increase the risk to the subject (for
             example: history of keloids, skin allergy, hypersensitivity or contact dermatitis,
             including previous reactions to dressings to be used in the study), as determined by
             the investigator.
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 65 Years

Patient description (medical language): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient description (patient's own words): I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Does the patient match the trial criteria? 0