Clinical trial NCT01953809 (phase 1, status: withdrawn)
Conditions: infections, bacterial
ICD codes: A49.9, A04.9, A04.8, A49.8
Drugs: gsk1322322, ee/ne, gsk1322322 placebo, ee/ne placebo
SMILES: CC1=NC(NNC(=O)[C@H](CC2CCCC2)CN(O)C=O)=C(F)C(=N1)N1CCN2CCOC[C@@H]2C1, [Ne], CC1=NC(NNC(=O)[C@H](CC2CCCC2)CN(O)C=O)=C(F)C(=N1)N1CCN2CCOC[C@@H]2C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    emerging gsk1322322 pre-clinical data id'd potentially reactive metabolites previously not seen
    that changed the risk: benefit profile and led to a termination
  
Eligibility criteria:

        Inclusion Criteria:

          -  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 that the finding is unlikely to introduce additional risk
             factors and will not interfere with the study procedures.

          -  Non smoking female (of childbearing age), between 18 and 45 years of age inclusive, at
             the time of signing the informed consent.

          -  A female subject is eligible to participate if she is of: Non-childbearing potential
             defined as pre-menopausal females with a documented tubal ligation or hysterectomy
             without oophorectomy (at least one functioning ovary required) or child bearing age
             with the presence of non-drug eluting intra uterine device (IUD) i.e. copper. NOTE:
             The IUD placement needs to be confirmed by an obstetrician-gynecologist.

          -  Subjects must be willing to use EE/NE in combination with one of the following
             appropriate contraceptive methods from at least 14 days prior to the first dose of
             study drug until completion of the follow-up visit Complete abstinence from
             intercourse for at least 14 days prior to the first dose of IP, throughout the study,
             and for the subsequent post study monitoring or; A barrier method plus a spermicide
             (e.g., condom or diaphragm with spermicidal foam/gel/cream/ suppository for at least
             14 days prior to the first dose of IP throughout the study, and for the subsequent
             post study monitoring or Sterilization (vasectomy) of male partner prior to
             commencement of female subject's last normal menstrual period prior to IP
             administration and the male partner is the sole partner for that female subject

          -  Body weight >=50 kilograms (kg) (110 pounds [lbs]) and <114kg (<250 lbs) and body mass
             index within the range 19 to 32 kg/meter^2 (inclusive).

          -  Alanine aminotransferase, alkaline phosphatase and bilirubin <=1.5xupper limit of
             normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated
             and direct bilirubin <35%) at screening and check-in (repeat allowed at check-in
             only).

          -  QT interval corrected for heart rate by Bazett's formula (QTcB) < 450 millisecond
             (msec) at screening and check-in.

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form

        Exclusion Criteria:

          -  Pregnant females as determined by positive human chorionic gonadotropin (hCG) test at
             screening or prior to dosing.

          -  History of any condition that would contraindicate Ortho-Novum administration
             (including hypertension, stroke, ischemic heart disease, venous thromboembolism or
             family history of thromboembolism, known factor V Leiden mutation or other gene
             mutations associated with increased risk of thromboembolism, migraine headaches,
             carcinoma of the breast, liver or endometrium, gallbladder disease, history of
             undiagnosed abnormal uterine bleeding, etc.

          -  Females with conditions or concurrent medications that could adversely affect hormone
             levels (e.g. oophorectomies).

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

          -  Endocrine system: untreated or unstable thyroid disorder and/or diabetes mellitus (I
             and II). Treatment of the condition must be stable for at least 4 weeks prior to first
             dose of study drug.

          -  Have suffered a urinary tract, bladder, or vaginal infection within 4 weeks prior to
             the first dose of study drug, or has a urinalysis result at Screening consistent with
             an urinary tract infection. Subjects diagnosed with an infection at Screening should
             be treated appropriately and may be re-screened after 4 weeks.

          -  Fasting triglycerides > 300 mg/deciliter (dL) at Screening.

          -  A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody, or a
             positive test for human immuno virus (HIV) antibody result within 3 months of
             screening.

          -  A positive pre-study drug/alcohol screen.

          -  History of regular alcohol consumption within 6 months of the study defined as An
             average weekly intake of >7 drinks for females. One drink is equivalent to 12 gram 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.

          -  Concurrent-medications that alter gastro-intestinal motility result in diarrhea or
             bind study drugs (for example erythromycin, antacids, prokinetic agents,
             cholestyramine).

          -  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.

          -  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 GlaxoSmithKline (GSK) Medical Monitor the medication will not
             interfere with the study procedures or compromise subject safety due to potential drug
             interaction.

          -  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 GSK
             Medical Monitor, contraindicates their participation.

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

          -  Lactating females.

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia.

          -  Urinary cotinine levels indicative of smoking or regular use of tobacco- or
             nicotine-containing products within 4 weeks prior to screening.

          -  Unable to refrain from consumption of red wine, seville oranges, grapefruit or
             grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit
             juices] from 7 days prior to the first dose of study medication.

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

        Female subjects with Heart rate <50 and >100 beats per minute (bpm), PR interval <120 and
        >220 msec, QRS duration <70 and >120 msec, QTcB >=450 msec (Note: The waveforms must enable
        the QT interval to be clearly defined), Q wave>30 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 bundle branch
        block, AV block (2nd degree or higher), Wolf Parkinson White (WPW) syndrome), sinus pauses>
        3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular
        ectopic beats) or any significant arrhythmia which, in the opinion of the principal
        investigator and GSK medical monitor, will interfere with the safety of the individual
        subject.