Clinical trial NCT01852565 (phase 1, status: completed)
Conditions: atherosclerosis
ICD codes: I67.2, I70.90, I70.91, I70.0, I70.1, I70.8, I25.83
Drugs: darapladib, diltiazem
SMILES: CCN(CC)CCN(CC1=CC=C(C=C1)C1=CC=C(C=C1)C(F)(F)F)C(=O)CN1C2=C(CCC2)C(=O)N=C1SCC1=CC=C(F)C=C1, COC1=CC=C(C=C1)[C@@H]1SC2=C(C=CC=C2)N(CCN(C)C)C(=O)[C@@H]1OC(C)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Male or female aged between 18 and 65 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 ECG.

          -  A subject with an alanine aminotransferase (ALT), aspartate aminotransferase (AST),
             alkaline phosphatase or bilirubin laboratory result outside the reference range may be
             included only if both the Investigator and the GSK Medical Monitor agree and document
             that the finding is unlikely to introduce additional risk factors and will not
             interfere with the study procedures.

          -  BMI within the range 19-37 kilogram per square meter (kg/m2) (inclusive).

          -  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
             [for this definition, "documented" refers to the outcome of the
             investigator's/designee's review of the subject's medical history for study
             eligibility, as obtained via a verbal interview with the subject or from the subject's
             medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in
             questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)
             > 40 milli-international units per milliliter (MlU/ml) and estradiol < 40
             picogram/milliliter [(pg/ml) (<147 pmol/L) is confirmatory].

          -  A female subject is eligible to participate if she is of Child-bearing potential and
             is abstinent or agrees to use one of the contraception methods for an appropriate
             period of time (as determined by the product label or investigator) prior to the start
             of dosing to sufficiently minimize the risk of pregnancy at that point. Female
             subjects must agree to use contraception until the final follow-up visit.

          -  A female subject is eligible to participate if she is of Child-bearing potential and
             has only same-sex partners, when this is her preferred and usual lifestyle.

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

          -  Single QT duration corrected for heart rate by Fridericia's formula (QTcF) < 450
             Millisecond (msec)

        Exclusion Criteria:

          -  A subject will not be eligible for inclusion in this study if any of the following
             criteria apply:

        Criteria Based Upon Medical Histories

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

          -  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.

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

          -  History of sensitivity to any of the study medications, including diltiazem, 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.

          -  Any contraindications for diltiazem administration.

          -  Any condition that, in the opinion of the investigator, presents undue risk from the
             study medications, including diltiazem, or procedures.

          -  Requiring the use of oral or injectable strong Cytochrome P450 (CYP3) A4 inhibitors or
             use of other CYP3A4 inhibitor/inducers within 14 days prior to dosing.

          -  History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions

          -  Clinical criteria for diagnosing anaphylaxis or severe allergic response. Criteria
             Based Upon Diagnostic Assessments

          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
             result within 3 months of screening

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for human immunodeficiency virus (HIV) antibody.

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

        Other Criteria

          -  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.

          -  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 GSK Medical Monitor the medication will not interfere with the study
             procedures or compromise subject safety.

          -  Unwillingness or inability to follow the procedures outlines in the protocol.

          -  Subject is mentally or legally incapacitated.

          -  Consumption of grapefruit or grapefruit juice within 7 days prior to the first dose of
             study medication.