Clinical trial NCT02289495 (phase 1, status: terminated)
Conditions: infection, human immunodeficiency virus
ICD codes: Z21
Drugs: gsk2838232, placebo, ritonavir
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CC(C)[C@H](N1CCCNC1=O)C(=O)N[C@H](C[C@H](O)[C@H](CC1=CC=CC=C1)NC(=O)COC1=C(C)C=CC=C1C)CC1=CC=CC=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Between 18 and 55 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.

          -  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.

          -  A Creatinine clearance (CLcr) >80 millilitre per minute (mL/min) as determined by
             Cockcroft-Gault equation where age is in years, weight (Wt) is in kg, and serum
             creatinine (Scr) is in units of milligram / decilitre (mg/dL); CLcr (mL/min) = (140 -
             age) * Wt / (72 * Scr) (times 0.85 if female).

          -  Body weight >= 50 kilogram (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 kilogram per meter square
             kg/m^2 (inclusive)

          -  Male or 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. 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 one week after the last dose of study medication. a) Vasectomy with
             documentation of azoospermia, b) Male condom plus partner use of one of the
             contraceptive options below: 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:

          -  Alanine aminotransferase and bilirubin >1.5xupper 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)

          -  Subjects who have asthma or a history of asthma.

          -  Medical history of cardiac arrhythmias or cardiac disease or a family and personal
             history of long QT syndrome.

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

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products within 6 months prior to screening.

          -  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. For
             potent immunosuppressive agents, subjects with presence of hepatitis B core antibody
             (HBcAb) should also be excluded.

          -  Screening or baseline cardiac troponin I greater than the 99% cutoff (>.045 nanogram/
             milliliter [ng/mL] by the Dimension Vista Cardiac troponin assay).

          -  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 products
             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 24-Hour Screening Holter: Any symptomatic arrhythmia (except
             isolated extra systoles), Sustained cardiac arrhythmias (such as atrial fibrillation
             or flutter, supraventricular tachycardia (>=10 consecutive beats), complete heart
             block). Non-sustained or sustained ventricular tachycardia (defined as >= 3
             consecutive ventricular ectopic beats). Any conduction abnormality (including but not
             specific to left or right incomplete or complete bundle branch block, atrioventricular
             (AV) block [2nd degree or higher], Wolff-Parkinson-White [WPW] syndrome etc.). Sinus
             Pauses > 3 seconds. 300 or more supraventricular ectopic beats in 24 hours. 250 or
             more ventricular ectopic beats in 24 hours.

          -  Any clinically significant abnormal echocardiogram finding. Abnormal echocardiogram
             findings should be discussed with the Medical Monitor prior to enrolment.

          -  Exclusion criteria for screening ECG (a single repeat is allowed for eligibility
             determination): Heart rate <45 and >100 beats per minute (bpm) (Males); <50 and >100
             bpm (Males); For both Males and Females: PR Interval <120 and >220 msec, QRS duration
             <70 and >120 millisecond (msec); QTc interval (Fridericia's) >450 msec. Notes: 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, AV block [2nd degree or
             higher], WPW syndrome). Sinus Pauses > 3 seconds. Any significant arrhythmia which, in
             the opinion of the principal investigator or GlaxoSmithKline medical monitor, will
             interfere with the safety for the individual subject. Non-sustained or sustained
             ventricular tachycardia (>= 3 consecutive ventricular ectopic beats).