Clinical trial: Relative Oral Bioavailability Study of Different Fixed Dose Combinations of Dolutegravir and Rilpivirine in Healthy Subjects (NCT02373930)

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
             and cardiac evaluation (history, electrocardiogram [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 in
             consultation with the medical monitor if required 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) (110 pounds [lbs]) for men and >=45 kg (99 lbs) for
             women and body mass index (BMI) within the range 18.5-31.0 kg/square meter (m^2)
             (inclusive).

          -  Male or Female- Female: Female subject of non-reproductive potential : is eligible to
             participate if she is not pregnant (as confirmed by a negative serum or urine 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 (refer to laboratory reference ranges for confirmatory levels).
        Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of
        post-menopausal status prior to study enrolment.

        Reproductive potential and agrees to follow one of the options listed below in the
        GlaxoSmithKline (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 medication and until at least five terminal half-lives (10 days) after the last
        dose of study medication and completion of the follow-up visit.

        GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of
        Reproductive Potential (FRP)

        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.

          -  Intrauterine device that meets the standard operating procedure (SOP) effectiveness
             criteria including a <1% rate of failure per year, as stated in the product label.

          -  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.

          -  Male condom combined with a vaginal spermicide (foam, gel, film, cream, or
             suppository).

        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.

        Male:

          -  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 five half-lives of study medication OR for a cycle of spermatogenesis
             following five terminal half-lives] after the last dose of study medication.

               1. Vasectomy with documentation of azoospermia.

               2. Male condom plus partner use of one of the contraceptive options below:

          -  Contraceptive subdermal implant that meets the 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 progestrogen alone.

          -  Injectable progestrogen.

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

        Exclusion Criteria:

          -  Alanine aminotransferase (ALT) and bilirubin >1.5x upper limit of normal (ULN)
             (isolated bilirubin >1.5xULN is acceptable if bilirubin is 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).

          -  Unable to refrain from the use of prescription or non-prescription drugs, including
             vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or
             14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is
             longer) prior to the first dose of study medication, unless in the opinion of the
             Investigator and GSK medical monitor the medication will not interfere with the study
             procedures or compromise subject safety.

          -  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 (g) of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5
             ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

          -  History of sensitivity to any of the study medications, or components thereof 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), positive hepatitis C antibody test
             result at screening or within 3 months prior to first dose of study treatment.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for HIV antibody.

          -  Where participation in the study would result in donation of blood or blood product in
             excess of 500 mL within 56 days.

          -  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 entities within 12 months prior to the first
             dosing day.

          -  Exclusion criteria for screening ECG (a single repeat is allowed for eligibility
             determination):

        Heart Rate for males: <45 and >100 beats per minute (bpm), females: <50 and >100 bpm PR
        Interval for males: <120 and >220 milliseconds (msec) QRS Interval for males: <70 and >120
        msec QT duration corrected for heart rate (QTc) interval (Fridericia's) for males: >450
        msec Note: A heart rate from 100 to 110 bpm can be rechecked by ECG or vitals within 30
        minutes to verify eligibility.

        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 (AV block) (2nd degree or higher), Wolf Parkinson
        White [WPW] syndrome).

        Sinus Pauses >3 seconds. Any significant arrhythmia which, in the opinion of the principal
        investigator OR GSK medical monitor, will interfere with the safety for the individual
        subject.

        Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic
        beats).

          -  Employment with Janssen and GSK or with the Investigator or study site, with direct
             involvement in the proposed study or other studies under the direction of that
             Investigator or study site, as well as family members of the employees or 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? Entailment