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: Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK2269557 Administered Via the ELLIPTA Dry Powder Inhaler to Healthy Subjects

Eligibility criteria:
Inclusion Criteria:

          -  Between 20 and 75 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
             and cardiac monitoring.

          -  Normal spirometry at Screening (forced expiratory volume in 1 second and forced vital
             capacity >=80% of predicted - measurements to be taken in triplicate and the highest
             value must be >=80% of predicted).

          -  A subject with a clinical abnormality or laboratory parameter(s) outside the reference
             range for the population being studied may be included only if the investigator, in
             consultation with the medical monitor if needed, agree and document that the finding
             is unlikely to introduce additional risk factors and will not interfere with the study
             procedures.

          -  Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 18 to 35
             kg/square meter (m^2) (inclusive).

          -  Male subjects. 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 at least 10 days after the last dose of study medication.

               -  Vasectomy with documentation of azoospermia.

               -  Male condom plus partner use of one of the contraceptive options: Contraceptive
                  subdermal implant, Intrauterine device or intrauterine system, Combined estrogen
                  and progestogen oral contraceptive, Injectable progestogen, Contraceptive vaginal
                  ring and Percutaneous contraceptive patches.

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

               -  Non-reproductive potential defined as: 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 (refer to laboratory reference ranges for confirmatory levels).
                  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.

               -  Female of reproductive potential (FRP) must agrees to the use of male condom with
                  spermicide in addition to one of the following methods from the list of highly
                  effective contraceptive methods from 30 days prior to the first dose of study
                  medication and until at least 10 days after the last dose of study medication:
                  Contraceptive subdermal implant; Intrauterine device or intrauterine system;
                  Combined estrogen and progestogen oral contraceptive; 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.

        The list does not apply to FRP with same sex partners or for subjects who are and will
        continue to be abstinent from penile-vaginal intercourse on a long term and persistent
        basis, when this is their preferred and usual lifestyle. Periodic abstinence (e.g.
        calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not
        acceptable methods of contraception.

        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 protocol.

        Exclusion Criteria:

          -  Asthma or a history of asthma (except in childhood, which has now remitted).

          -  Alanine Aminotransferase (ALT) and bilirubin >1.5 Upper Limit of Normal (ULN)
             (isolated bilirubin >1.5xULN is acceptable if fractionated and direct bilirubin <35%)

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

          -  Corrected QT interval by Fridericia's formula (QTcF) > 450 milliseconds (msec).

          -  Unable to refrain from the use of prescription drugs (except contraceptives and HRT)
             or non-prescription drugs (except acetaminophen), including vitamins, herbal and
             dietary supplements from 7 days before the first dose of study medication until the
             follow-up visit, unless in the opinion of the Investigator and GlaxoSmithKline (GSK)
             Medical Monitor the medication will not interfere with the study procedure or
             compromise subject safety.

          -  The subject has received any type of vaccination within 4 weeks of their first dose of
             study medication, or is expected to be vaccinated within 4 weeks after their last dose
             of study medication.

          -  Current smoker or a history of smoking within 6 months of Screening, or a total pack
             year history of >5 pack years. (number of pack years = [number of cigarettes per
             day/20] x number of years smoked)

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

          -  Unable to refrain from the consumption of Seville oranges, grapefruit or grapefruit
             juice, pummelos, exotic citrus fruits, or grapefruit hybrids from 7 days before all
             doses of study medication and until collection of the final pharmacokinetic sample in
             each study period.

          -  History of sensitivity to any of the study medications, or components thereof
             (including lactose and Magnesium stearate) or a history of drug or other allergy that,
             in the opinion of the investigator or Medical Monitor, contraindicates their
             participation.

          -  Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test
             result at screening or within 3 months prior to first dose of study treatment.
             Subjects with a positive Hepatitis C antibody due to prior resolved disease can be
             enrolled, only if a confirmatory negative Hepatitis C Ribonucleic acid (RNA)
             polymerase chain reaction (PCR) test is obtained.

          -  A positive test for Human Immunodeficiency Virus(HIV) antibody (according to local
             policies).

          -  A positive drug/alcohol screen at screening or on admission (Day -1). - Where
             participation in the study would result in donation of blood or blood products in
             excess of 500 mL within a 90 day period.

          -  The subject has participated in a clinical trial and has received an investigational
             product (excluding participation in Part A of this study) 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 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 20 Years old.
Subject must be at most 75 Years

Eligibility (NLI label): Contradiction