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OpenTrials
Completed

NCT Number: NCT01218204

A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Administering Multiple Oral Doses of GSK1292263 Alone and With Atorvastatin

This study investigates the safety, pharmacokinetics and effects of GSK1292263 when taken alone or when co-dosed with atorvastatin to subjects with dyslipidemia.

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Key information

Conditions

Dyslipidaemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GSK Investigational Site, Anniston, Alabama, United States

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About this study

This compound has been studied in healthy subjects and subjects with type II diabetes and is now being studied in subjects with dyslipidemia. Because many patients with dyslipidemia are on statins, it is important to study how GSK1292263 behaves when taken with a potent statin, atorvastatin. The cholesterol lowering drug, ezetimibe, is included for comparison.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy adult males and females of non-child-bearing-potential, aged 18-75 years who is capable of giving 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; or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol <40 pg/ml (<140 pmol/L) is confirmatory in the absence of a clear post-menopausal history.
  • Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study.
  • Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until seven days following the last dose.
  • Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19.0 and 39.0 (inclusive).
  • Part A: (i) Subjects who are on 80mg or 40mg atorvastatin for >= 4 weeks and are tolerating the drug well, or (ii) Subjects not on lipid-modifying therapy who have a fasting low density lipoprotein cholesterol (LDLc) >= 130mg/dL.
  • In Part B at Screening: Subjects who are on statins or Vytorin treatment for >= 4 weeks.
  • Part B at the end of the 4 week washout: Subjects who have a fasting LDL cholesterol of >=120mg/dL and <=180mg/dL and fasting triglycerides of >=100mg/dL and <=400mg/dL.
  • Part B at the end of the 4 week run-in on atorvastatin: Subjects who are tolerating well atorvastatin 10mg or 80mg (as determined by the Investigator).
  • Part B: Subjects must be willing to discontinue statins or Vytorin for the duration of the study.
  • Liver enzymes, AST and ALT < 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin =< 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Subjects with Gilbert's syndrome are allowed to participate in the study.
  • Average QTcB or QTcF < 450msec; or QTc < 480msec in subjects with right bundle branch block.

Exclusion criteria

  • A medical history of the following:
  • Clinical or angiographic cardiovascular disease, including history or current evidence of coronary heart disease, heart failure, cerebrovascular disease (including stroke and transient ischemic attack [mini-stroke]), peripheral vascular disease. Subjects pending diagnostic procedures for any of those conditions at the time of screening will not be eligible for participation.
  • Homozygous familial hypercholesterolemia or family history of familial hypercholesterolemia (Part B only). Note: Subjects with heterozygous familial hypercholesterolemia on 80mg atorvastatin who are tolerating this drug well and fulfill the other eligibility criteria may participate in Part A only.
  • History of recurrent or unexplained muscle aches (e.g., fibromyalgia), myopathy or myositis, whether or not it is related to treatment with statins or other lipid modifying drugs.
  • Renal impairment as defined by a calculated glomerular filtration rate < 60 mL/min
  • History of diabetes mellitus, or history of post-prandial and/or random blood glucose > 200 mg/dl or fasting glucose > 125 mg/dL or currently taking diabetes medications to manage fasting glucose levels (e.g., thiazolidinediones, sulfonylureas, insulin, metformin).
  • History of pancreatitis within 10 years of screening.
  • Any concurrent serious illness (e.g., severe chronic obstructive pulmonary disease, sleep apnea, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject from completing the study.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
  • Active peptic ulcer disease and/or history of peptic ulcer disease or gastrointestinal bleeding within 12 months prior to screening.
  • History of kidney stones within 10 years of screening.
  • History of uncorrected thyroid dysfunction or an abnormal thyroid function test assessed by thyroid stimulating hormone (TSH) at Screening. (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 3 months prior to screening and who have a screening TSH within the normal range may participate.)
  • Symptomatic cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to screening.
  • Gastrointestinal disease that could affect fat or bile acid absorption, or the pharmacokinetics or pharmacodynamics of the study drugs, including inflammatory bowel disease, chronic diarrhea, Crohn's disease or malabsorption syndromes within the past year.
  • Gastrointestinal surgery that may affect the pharmacokinetics or pharmacodynamics of the study drugs.

Note: Subjects may be enrolled in the study if they have had a cholecystectomy three or more months before the time of screening and are stable and asymptomatic.

  • Subjects taking ezetimibe monotherapy, fibrates, bile acid binding resins, nicotinic acid or fat absorption inhibitors are not eligible for Parts A and B.
  • For females a hemoglobin < 11.5g/dL, and for males a hemoglobin < 12.5g/dL.
  • Current inadequately controlled hypertension (blood pressure >= 160mmHg systolic or >= 100mmHg diastolic at screening). If blood pressure medication is changed as a result of screening, blood pressure will be re-measured after 6 weeks and must again meet these criteria.
  • Significant electrocardiogram (ECG) abnormalities, defined as follows:

Heart Rate < 50 and >100bpm PR Interval <120 and > 220ms QRS duration < 70 and >120ms QTC Interval (Bazett) > 450ms Or, has clinically significant rhythm abnormalities identified during 24-hour screening Holter assessment. Subjects with left bundle branch block are excluded from the study. Subjects with partial right bundle branch block may be considered for inclusion following consultation with the GlaxoSmithKline (GSK) Medical Monitor. Subjects with Wolf-Parkinson-White (WPW) syndrome are excluded from the study.

  • Creatinine phosphokinase (CPK) >= 2x ULN at screening.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • A positive test for HIV antibody.
  • The subject has a positive pre-study drug-of-abuse screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
  • Subjects will be excluded if they require treatment with systemic corticosteroids.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • History of sensitivity or untoward reaction to the study medications (GSK1292263, atorvastatin or ezetimibe), or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
  • History of intolerance to statins.
  • Any change in concomitant medication (including multivitamins, herbal remedies, dietary supplements, and over-the-counter medication) within six weeks prior to screening that is not approved by GSK.
  • On a diet that may affect study outcomes, or any change in diet, exercise habits or smoking status within six weeks prior to screening or planned change during study (e.g., new exercise program) other than that in the dietary instructions in the Study Procedures Manual.
  • 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.
  • Where participation in study would result in donation of blood in excess of approximately 500mL within a 56 day period.
  • Subject is mentally or legally incapacitated.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Pregnant females as determined by positive urine hCG test at screening or prior to dosing.
  • Lactating females.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • 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.
  • Unwilling to abstain from caffeine-or xanthine-containing products from Day -2 until Day 15.
  • Subject is either an immediate family member of a participating investigator, study coordinator, employee of an investigator; or is a member of the staff conducting the study.

Treatment and study plan

10mg atorvastatin

Drug

10mg

Other names: Lipitor

80mg atorvastatin

Drug

80mg

Other names: Lipitor

GSK1292263 Placebo

Drug

Placebo

100mg GSK1292263

Drug

100mg

300mg GSK1292263

Drug

300mg

800mg GSK1292263

Drug

800mg

10mg Ezetimibe

Drug

10mg

Other names: Zetia

Washout

Other

No interventions - washout period

Primary outcomes

  1. Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A

    Time frame: Up to Day 26

    An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.

  2. Number of Participants With Any AEs and SAEs- Part B (Washout)

    Time frame: Up to Day 28

    An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.

  3. Number of Participants With Any AEs and SAEs- Part B (Run-in)

    Time frame: Up to Day 28

    An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.

  4. Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm)

    Time frame: Up to Day 26

    An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.

  5. Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A

    Time frame: Up to Day 26

    Single ECGs were taken after admission on Day -1 and at Follow-up (up to Day 26). On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No value found to be abnormal clinically significant in Part A of the study.

  6. Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout)

    Time frame: Up to Day 28

    ECGs were taken at Screening, and on Day1 and Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings.

  7. Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in)

    Time frame: Day 28

    ECGs were taken on Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No data found to be abnormal clinically significant in run-in phase.

  8. Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm)

    Time frame: Up to Day 26

    Single ECGs were taken after admission on Day -2, and pre-breakfast on Days -1, 4, 10, and at Follow-up. On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. The data was found to be abnormal clinically significant in treatment phase.

  9. Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A

    Time frame: Up to Day 26

    Assessment of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate was performed after admission on Day -1 and at Follow-up. On Days 1, 7 and 14, they were taken at pre-dose, 1, 3, 6, 8, 14 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.

  10. Number of Participants With Vital Signs of PCI- Part B (Washout)

    Time frame: Up to day 28

    Assessment of vital signs including SBP, DBP heart rate was performed at Screening, on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.

  11. Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in)

    Time frame: Up to day 28

    Assessment of vital signs including SBP, DBP and heart rate was performed on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.

  12. Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm)

    Time frame: Up to Day 26

    Assessment of vital signs including SBP, DBP and heart rate was performed after admission on Day-2, and pre-breakfast on Days -1, 4, and 10 in a fasting state early in the morning (prior to dosing), and at Follow-up. On Days 1, 7 and 14, they were also be taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.

  13. Number of Participants With Abnormal Hematology Value of PCI- Part A

    Time frame: Up to Day 26

    Blood samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Data for only those parameters (Hematocrit, Hemoglobin and Total neutrophils) are presented for which findings are of PCI either high or low.

  14. Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout)

    Time frame: Up to Day 28

    Blood samples were collected at screening, and on Days 1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (White blood cells [WBC], Total neutrophils, Hematocrit and Lymphocytes) are presented for which findings are of PCI either high or low.

  15. Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in)

    Time frame: Days 14 and 28

    Blood samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Lymphocytes) are presented for which findings are of PCI either high or low.

  16. Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm)

    Time frame: Up to Day 26

    Blood samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24hrs post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24hrs post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Platelet count, Total neutrophils and Lymphocytes) are presented for which findings are of PCI either high or low.

  17. Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A

    Time frame: Up to Day 26

    Samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). No parameter was found to have any value of PCI.

  18. Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout)

    Time frame: Up to Day 28

    Samples were collected at screening, and on Days1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Inorganic phosphorus, Sodium, Alanine aminotransferase [ALT], Potassium, Creatinine, Calcium, magnesium, Glucose, Total Bilirubin, Carbon dioxide/bicarbonate [CO2/HCO3] and Aspartate aminotransferase [AST]) are presented for which findings are of PCI either high or low.

  19. Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in)

    Time frame: Days 14 and 28

    Samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Glucose, Magnesium, ALT, AST, Calcium, Inorganic phosphorus and Total bilirubin) are presented for which findings are of PCI either high or low.

  20. Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm)

    Time frame: Up to Day 26

    Samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24 hours post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Glucose, Total bilirubin, Albumin, Magnesium, CO2/HCO3, Calcium, ALT, AST, Inorganic phosphorus, Potassium and Sodium) are presented for which findings are of PCI either high or low.

  21. Maximum Observed Concentration (Cmax) of GSK1292263- Part A

    Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    Serial blood samples for the determination of the PK for GSK1292263 on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).

  22. Cmax of GSK1292263- Part B (Pooled Treatment Arm)

    Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).

  23. Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A

    Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).

  24. Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A

    Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    Serial blood samples for the determination of the PK for GSK1292263 on Days 1 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48h sample on Day 1).

  25. Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm)

    Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).

  26. Tlag of GSK1292263- Part B (Pooled Treatment Arm)

    Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.

    Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.

  27. Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A

    Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).

  28. AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm)

    Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).

  29. Trough Concentration of GSK1292263

    Time frame: On Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    Trough samples for GSK1292263 PK (all treatment arms) were planned to be collected early in the morning on Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48h PK sample was collected on Day 16). (pre-dose for Days 13 and 14; trough Day 15 = 24h post last dose; trough Day 16 = 48h post last dose).

  30. Cmax of Atorvastatin- Part A

    Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.

    Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).

  31. Cmax of Atorvastatin- Part B (Pooled Treatment Arm)

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).

  32. Tmax of Atorvastatin- Part A

    Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.

    Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).

  33. Tmax of Atorvastatin- Part B (Pooled Treatment Arm)

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).

  34. AUC (0-24) of Atorvastatin- Part A

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).

  35. AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm)

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).

  36. Trough Concentration of Atorvastatin

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were planned to be collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were planned to be collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were planned to be collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was planned to be collected on Day 16).

  37. Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14

    Time frame: Baseline and Day 14

    Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.

  38. Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours)

    Time frame: Baseline and Day 14

    Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.

  39. Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours)

    Time frame: Baseline and Day 14

    Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.

  40. Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours)

    Time frame: Baseline and Day 14

    Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.

  41. Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14

    Time frame: Baseline and Day 14

    Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was Day -1 value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.

Secondary outcomes

  1. Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A

    Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.

    Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).

  2. Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).

  3. Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A

    Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.

    Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).

  4. Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose and on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).

  5. AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A

    Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.

    Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).

  6. AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).

  7. Trough Concentration of Atorvastatin Metabolite (2-Hydroxyatorvastatin)

    Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

    For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were supposed to collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were supposed to collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were supposed to collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). However no data was collected.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Important dates

Study start
2010
Primary completion
2011
Study completion
2011
First posted
Oct 11, 2010
Registry last updated
Jul 16, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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