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

Completed · Phase 2 · Has a placebo group

Conditions studied: Dyslipidaemias, Dyslipidemias

In brief

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

Key facts

Study ID

NCT01218204

Run by

GlaxoSmithKline

People needed

287

Starts

2010-09-14

Expected to finish

2011-06-29

Last updated by the study team

2019-07-16

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• GSK Investigational Site — Anniston, Alabama, United States
• GSK Investigational Site — Chula Vista, California, United States
• GSK Investigational Site — Stockton, California, United States
• GSK Investigational Site — Jacksonville, Florida, United States
• GSK Investigational Site — Miami, Florida, United States
• GSK Investigational Site — Miami, Florida, United States
• GSK Investigational Site — Port Orange, Florida, United States
• GSK Investigational Site — St. Petersburg, Florida, United States
• GSK Investigational Site — Chicago, Illinois, United States
• GSK Investigational Site — Chicago, Illinois, United States
• GSK Investigational Site — Louisville, Kentucky, United States
• GSK Investigational Site — Kalamazoo, Michigan, United States
• GSK Investigational Site — Minneapolis, Minnesota, United States
• GSK Investigational Site — Berlin, New Jersey, United States
• GSK Investigational Site — Cincinnati, Ohio, United States
• GSK Investigational Site — Oklahoma City, Oklahoma, United States
• GSK Investigational Site — Eugene, Oregon, United States
• GSK Investigational Site — Spartanburg, South Carolina, United States
• GSK Investigational Site — San Antonio, Texas, United States
• GSK Investigational Site — San Antonio, Texas, United States
• GSK Investigational Site — Renton, Washington, United States

Full record on ClinicalTrials.gov

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