Patient case (clinical description): 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's own account: 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.

Clinical trial: Placebo and Moxifloxacin Controlled Cardiac Conduction Study of GSK2140944 in Healthy Volunteers

Eligibility criteria:
Inclusion Criteria:

          -  Male or female between 18 and 55 years of age, inclusive, at the time of signing the
             informed consent

          -  Healthy as determined by a responsible and experienced physician, based on a medical
             evaluation including medical history, physical examination, laboratory tests, and
             cardiac monitoring. A subject with a clinical abnormality or laboratory parameters
             outside the reference range for the population being studied may be included only if
             the investigator feels and documents that the finding is unlikely to introduce
             additional risk factors and will not interfere with the study procedures.

          -  Body weight >= 50 kilogram (kg) and body mass index within the range 19 to 31 kilogram
             / square meter (kg/m^2) (inclusive).

          -  A female subject is eligible to participate if she is not pregnant (as confirmed by a
             negative serum beta-human chorionic gonadotrophin test), not lactating, and at least
             one of the following conditions applies:

          -  Nonreproductive potential defined as:

          -  Premenopausal 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. To confirm
             postmenopausal status, a blood sample for simultaneous follicle-stimulating hormone
             (FSH) >40 milli-international units per mililiter (mlU/mL) and estradiol <40
             picogram/milliliter (pg/mL) (<147 picomole/liter [pmol/L]) is confirmatory. 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 postmenopausal status prior to study enrolment.

          -  Reproductive potential and agrees to follow one of the options listed below in the GSK
             Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of
             Reproductive Potential (FRP) requirements from 30 days prior to the first dose of
             study drug and until at least 7 days after the last dose of study drug and completion
             of the follow-up visit.

          -  This list does not apply to FRP with same sex partners, when this is their preferred
             and usual lifestyle or for subjects who are and will continue to be abstinent from
             penile-vaginal intercourse on a long-term and persistent basis.

          -  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, male
             partner sterilization with documentation of azoospermia prior to the female subject's
             entry into the study, and this male is the sole partner for that subject.

          -  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 as described in protocol, which includes
             compliance with the requirements and restrictions listed in the consent form and in
             the protocol

          -  Alanine aminotransferase (ALT) and bilirubin <1.5 × upper limit of normal range (ULN).
             Isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct
             bilirubin <35%. One repeat test to confirm result is acceptable.

          -  Serum potassium, calcium, and magnesium laboratory parameters within normal limits at
             screening and check-in.

        Exclusion Criteria:

          -  History/evidence of any arrhythmia (for example, second- or third-degree heart block,
             atrial fibrillation, supraventricular tachycardia, symptomatic sinus bradycardia,
             junctional rhythm) or clinically significant cardiac disease or procedure (mitral
             valve regurgitation, heart murmur, angina/ischemia, congenital heart abnormalities,
             coronary artery bypass grafting surgery, or percutaneous transluminal coronary
             angioplasty). A history of additional risk factors for torsades de pointes (e.g.,
             heart failure, hypokalemia, and family history of long QT syndrome).

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

          -  Any clinically significant CNS (e.g., seizures), cardiac, pulmonary, metabolic, renal,
             hepatic, or GI conditions or history of such conditions that, in the opinion of the
             investigator, may place the subject at an unacceptable risk as a participant in this
             trial or may interfere with the absorption, distribution, metabolism, or excretion of
             drugs.

          -  History of photosensitivity to quinolones.

          -  Use of systemic antibiotic within 30 days of screening.

          -  Confirmed lifetime history of C. difficile diarrhea

          -  History of spontaneous tendon rupture

          -  History of smoking or use of nicotine containing products within 3 months of screening
             or a positive urine cotinine indicative of smoking at screening.

          -  History of regular alcohol consumption within 6 months of the study defined as an
             average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
             equivalent to 12 grams of alcohol: 12 fluid ounces (fl oz) (360 millilitre [mL]) of
             beer, 5 fl oz (150 mL) of wine, or 1.5 fl oz (45 mL) of 80-proof distilled spirits.

          -  History of sensitivity to any of the study drugs or components thereof or a history of
             drug or other allergy that, in the opinion of the investigator or GSK medical monitor,
             contraindicates the potential subject's participation.

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical
             research unit uses heparin to maintain IV cannula patency).

          -  A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody
             result within 3 months of screening or positive human immunodeficiency virus (HIV)
             antibody.

          -  A positive urine test for drugs of abuse at screening or at Day -1; positive urine
             test for alcohol (or alcohol breath test) within 24 hours of any dose in the study.

          -  Exclusion criteria for screening and baseline ECG (a single repeat test is allowed for
             eligibility determination): Heart rate: <40 and >100 beats per minute (bpm) (For
             males), <45 and >100 bpm (For Females); PR interval<120 and >220 millisecond (msec);
             QRS duration<70 and >110 msec; QTcF interval>450 msec.

          -  Evidence of previous myocardial infarction (does not include ST-segment changes
             associated with repolarization).

          -  Any conduction abnormality (including but not specific to left or right complete
             bundle branch block, atrioventricular block [second degree or higher],
             Wolff-Parkinson-White syndrome), sinus pauses >3 seconds, non-sustained or sustained
             ventricular tachycardia (>3 consecutive ventricular ectopic beats), or any significant
             arrhythmia that, in the opinion of the investigator and GSK medical monitor, will
             interfere with the safety of the individual subject.

          -  An abnormal finding of clinical significance in the arrhythmia detection Holter
             performed on Day -2, which in the view of the investigator would compromise subject
             safety or interfere with study procedures or assessments will be excluded from the
             study. Full disclosures will be reviewed in detail and the review maintained as part
             of the subject's source documents. Analysis of the Holter recordings will consider the
             following:

          -  Heart rate (significant brady- or tachycardia, based on investigator's judgment)

          -  Reports of symptomatic arrhythmia (except isolated extrasystoles)

          -  Normal and aberrant beats

          -  Number of supraventricular contractions, premature atrial contractions, premature
             ventricular contractions, couplets, triplets, and ventricular tachycardias

          -  Atrioventricular conduction defects

          -  Atrial fibrillation and flutter

          -  Participation in the study would result in a donation of blood or blood products in
             excess of 500 mL within a 56-day period.

          -  Participation in a clinical trial in which the subject 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 4 new chemical entities within 12 months prior to the first
             dosing day.
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 55 Years

Eligibility (NLI label): Contradiction